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    • National Cancer Institute - Central IRB
    • 52 Trials Available
    • CONTACT US

    TRIAL NUMBER: EA2176

    Title: A Randomized Phase III Study of Immune Checkpoint Inhibition with Chemotherapy in Treatment-Naïve Metastatic Anal Cancer Patients

    Purpose:

    Primary Outcome Measures :
    1. Progression-free survival [ Time Frame: Up to 2 years ]
      Defined as the first of progressive disease or death due to any cause. Analyzed using a stratified two-sided overall 0.05 level log-rank test. Will utilize standard Eastern Cooperative Oncology Group -American College of Radiology Imaging Network interim monitoring for efficacy evaluation.


    Secondary Outcome Measures :
    1. Objective response rate (ORR) [ Time Frame: Up to 2 years ]
      ORR is the ratio of the number of patients with a complete response or partial response, as defined by Response Evaluation Criteria in Solid Tumors version 1.1, to the total number of treated patients.

    2. Overall survival [ Time Frame: Time between treatment randomization and death by any cause, assessed up to 2 years ]
      Evaluated by a stratified log-rank test, and using a two-sided 0.05 level Cochran Mantel-Haenzel.

    3. Incidence of adverse events [ Time Frame: Up to 2 years ]
      Analyses of toxicity will be via frequency tabulations and percentages by worst degree of toxicity and comparisons will be done via chi-square or Fisher's exact tests as appropriate.

    TRIAL NUMBER: A031803

    Title: PHASE II TRIAL OF INTRAVESICAL GEMCITABINE AND MK-3475 (PEMBROLIZUMAB) IN THE TREATMENT OF PATIENTS WITH BCG- NRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER

    Purpose:

    Primary Outcome Measures :
    1. Complete response rate in the carcinoma in situ (CIS) subpopulation [ Time Frame: At 6 months ]
      A complete response, only for patients with a CIS component, is a cystoscopy without evidence of bladder tumor, negative biopsy (including directed biopsies to any suspicious areas and in addition random bladder biopsies including trigone, left lateral wall, right lateral wall, posterior bladder, dome of bladder, and the prostatic urethra in men) and negative cytology for high grade disease at 6 months (end of cycle 8, week 25).

    2. Event-free survival at 18 months [ Time Frame: From the date of study registration to the first documentation of an event or death whichever comes first, assessed up to 18 months ]
      EFS will be measure from the date of study registration to the first documentation of an event or death whichever comes first. For patients without a documented event and who are still alive, they will be censored at last disease assessment. For patients who start any subsequent ant-cancer therapy without any reported events will be censored at their last disease assessment. will be obtained with a Kaplan-Meier estimator (using the Greenwood formula to estimate the variance) for the entire 155 patient group consisting of patients with CIS, CIS with Ta/T1 or Ta or T1 disease. A 90% confidence interval will be generated for the 18-month EFS estimate.


    Secondary Outcome Measures :
    1. Incidence of adverse events [ Time Frame: Up to 5 years post treatment ]
      Adverse events will be assessed based on the National Cancer Institute (NCI) common toxicity criteria (Common Terminology Criteria for Adverse Events [CTACAE] version [v] 5.0).

    2. Duration of response (DOR) [ Time Frame: From the time a patient had a documented response that had been confirmed (the time would start at the time a response was first noted) until disease-progression, assessed up to 5 years ]
      Analysis will only include those patients with a confirmed response. Patients who are alive and without a documented progression at the time of analysis will be censored at the time of the last disease status evaluation. The Kaplan-Meier product-limit estimator will be used to estimate DOR, medians and 95% confidence intervals (CI).

    3. Progression-free survival (PFS) [ Time Frame: From the date of study registration to the date of progression or death due to any cause, whichever occurs first, assessed up to 5 years ]
      Surviving patients without any documented progressions will be censored at the date of last known contact. Progression will be defined as the development of muscle invasive bladder cancer or metastatic urothelial cancer (nodal and/or distant). The Kaplan-Meier product-limit estimator will be used to estimate PFS, medians and 95% CI.

    4. Overall survival (OS) [ Time Frame: From the date of study registration to date of death due to any cause, assessed up to 5 years ]
      Surviving patients will be censored at the date of last known contact. The Kaplan-Meier product-limit estimator will be used to estimate OS, medians and 95% CI.

    5. Cystectomy-free survival [ Time Frame: From the date of study registration to the date of cystectomy for all patients ]
      The Kaplan-Meier product-limit estimator will be used to estimate cystectomy-free survival, medians and 95% CI.

    6. Recurrence free survival (RFS) [ Time Frame: From the date of study registration to the first documentation of recurrence or death due to any cause, assessed up to 5 years ]
      Surviving patients without any documented recurrence will be censored at the date of last known contact. Recurrence will be defined as the development of high-grade bladder cancer for patients with a CIS component only and those without a CIS component. The Kaplan-Meier product-limit estimator will be used to estimate RFS, medians and 95% CI.

    TRIAL NUMBER: EA8185

    Title: Phase 2 Study of Bladder-SparIng ChemoradiatioN with MEDI4736 (Durvalumab) in clinical Stage 3, Node PosItive bladdeR cancEr (INSPIRE)

    Purpose:

    Primary Outcome Measures :
    1. Clinical complete response (CR) [ Time Frame: Up to 6 years ]

    Secondary Outcome Measures :
    1. Metastasis-free survival [ Time Frame: From randomization to first evidence of metastatic disease or death from any cause, assessed up to 6 years ]
      Will be estimated by the Kaplan-Meier method.

    2. Bladder-intact event-free survival (BI-EFS) [ Time Frame: From randomization to the first BI-EFS event, assessed up to 6 years ]
      Will be estimated by the Kaplan-Meier method.

    3. Bladder cancer specific survival [ Time Frame: From randomization to death from bladder cancer, assessed up to 6 years ]
      Will be estimated by the Kaplan-Meier method.

    4. Overall survival [ Time Frame: From randomization to death from any cause, assessed up to 6 years ]
      Will be estimated by the Kaplan-Meier method.

    5. Progression-free survival [ Time Frame: From randomization to first of local progression, nodal or distant metastasis, or death from any cause, assessed up to 6 years ]
      Will be estimated by the Kaplan-Meier method.

    6. Complete response duration [ Time Frame: From the date of the biopsy documenting the complete response to the time of muscle invasive recurrence, local progression, evidence of metastatic disease or death due to any cause, assessed up to 6 years ]
      Stratified Cox proportional hazards models will be used to estimate hazard ratios in all eligible patients.

    7. Salvage cystectomy rate [ Time Frame: Up to 6 years ]
      Rate will be reported as a proportion of patients who do not experience clinical benefit after chemoradiotherapy (chemoRT) +/- MEDI4736 (durvalumab) along with a 90% confidence interval. Stratified Cox proportional hazards models will be used to estimate hazard ratios in all eligible patients.

    8. Incidence of adverse events [ Time Frame: Up to 1 year ]
      Assessed using the Common Terminology Criteria for Adverse Events (CTCAE). Toxicity will be evaluated in all treated patients, regardless of eligibility.

    TRIAL NUMBER: S1600

    Title: A Randomized Phase III Double-Blind Clinical Trial Evaluating the Effect of Immune-Enhancing Nutrition on Radical Cystectomy Outcomes

    Purpose: This randomized phase III trial studies how well nutrition therapy works in improving immune system in patients with bladder cancer that can be removed by surgery. Improving nutrition before and after surgery may reduce the infections and other problems that sometimes occur after surgery.

    TRIAL NUMBER: S1806

    Title: S1806: Phase III Randomized Trial of Concurrent Chemoradiotherapy with or Without Atezolizumab in Localized Muscle Invasive Bladder Cancer

    Purpose: This phase III trial studies how well chemotherapy and radiation therapy work with or without atezolizumab in treating patients with localized muscle invasive bladder cancer. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as gemcitabine, cisplatin, fluorouracil and mitomycin-C, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with radiation therapy may kill more tumor cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving atezolizumab with radiation therapy and chemotherapy may work better in treating patients with localized muscle invasive bladder cancer compared to radiation therapy and chemotherapy without atezolizumab.

    TRIAL NUMBER: A071701

    Title: Genomically-Guided Treatment Trial in Brain Metastases

    Purpose:

    Primary Outcome Measures :
    1. Objective response rate in the brain [ Time Frame: Up to 5 years ]
      Assessed per Response Assessment in Neuro-Oncology (RANO) criteria for brain metastases. The response rate is defined as the number of patients who have achieved complete response (CR) or partial response (PR) per RANO for brain metastases criteria during treatment with CDK, PI3K, or NTRK/ROS inhibitors divided by total number of evaluable patients. The response rate and associated exact confidence interval will be estimated within each cohort defined by the targeted agent and histology.


    Secondary Outcome Measures :
    1. Systemic response for extracranial disease [ Time Frame: Up to 5 years ]
      Assessed with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Will be estimated using the systemic response rate (SRR) - where SRR is defined as the number of evaluable patients achieving a response (PR or CR per RECIST 1.1) during treatment with study therapy divided by the total number of evaluable patients. Point estimates will be generated for systemic response rates within each cohort with corresponding 95% binomial confidence intervals.

    2. Clinical benefit rate for central nervous system (CNS) [ Time Frame: Up to 5 years ]
      Evaluated by Response Assessment in Neuro-Oncology (RANO) criteria. Will be estimated as the number of evaluable patients achieving stable disease (SD), partial response (PR), or complete response (CR) as their best objective response during treatment with protocol therapy divided by the total number of evaluable patients. Point estimates will be generated for clinical benefit rates within each cohort with corresponding 95% binomial confidence intervals.

    3. Clinical benefit rate for extracranial disease [ Time Frame: Up to 5 years ]
      Assessed by Response Evaluation Criteria in Solid Tumors (RECIST). Will be estimated as the number of evaluable patients achieving stable disease (SD), partial response (PR), or complete response (CR) as their best objective response (per RECIST for extracranial disease) during treatment with protocol therapy divided by the total number of evaluable patients. Point estimates will be generated for clinical benefit rates within each cohort with corresponding 95% binomial confidence intervals.

    4. Duration of response for brain metastases [ Time Frame: From the time measurement criteria are met for CR or PR for brain metastases until the first date that progressive CNS disease or death is documented, assessed up to 5 years ]
      Duration of response for brain metastases is defined for all evaluable patients who have achieved a confirmed response as the time from the date at which the patient's objective status for brain metastases is first noted to be a CR or PR (per Response Assessment in Neuro-Oncology [RANO] for brain metastases) to the date of the earliest progressive CNS disease is documented or death. The median and 95% confidence intervals will be estimated using the Kaplan-Meier estimator. No formal comparison will be made among the cohorts.

    5. Duration of response for extracranial disease [ Time Frame: From the time measurement criteria are met for CR or PR for extracranial disease until the first date that progressive disease for extracranial disease or death is documented, assessed up to 5 years ]
      Duration of response for extracranial disease is defined for all evaluable patients who have achieved a confirmed response as the time from the date at which the patient's objective status for extranial disease is first noted to be a CR or PR (per RECIST1.1) to the date of the earliest progression (PD) for extracranial disease is documented or death. The median and 95% confidence intervals will be estimated using the Kaplan-Meier estimator. No formal comparison will be made among the cohorts.

    6. Progression-free survival (PFS) - intracranial [ Time Frame: From first day of study treatment to the earliest date documentation of intracranial disease progression or death from any cause, assessed up to 5 years ]
      Intracranial PFS is defined as the time from the first day of study treatment to the earliest date of intracranial disease progression (per RANO for brain metastases) or death from any cause, whichever comes first. The median and 95% confidence intervals will be estimated using the Kaplan-Meier estimator. No formal comparison will be made among the cohorts.

    7. Progression-free survival (PFS) - extracranial [ Time Frame: From the first day of study treatment to the earliest date of documentation of extracranial disease progression or death from any cause, assessed up to 5 years ]
      Extracranial PFS is defined as the time from the first day of study treatment to the earliest date of extracranial disease progression (per RECIST1.1) or death from any cause, whichever comes first. The median and 95% confidence intervals will be estimated using the Kaplan-Meier estimator. No formal comparison will be made among the cohorts.

    8. Site of first progression [ Time Frame: Up to 24 months ]
      The site of first progression will be estimated descriptively within each cohort within 12 and 24 months after starting protocol treatment. The first progression is defined as the first documented central nervous system (CNS) progression per Response Assessment in Neuro-Oncology (RANO) or extracranial progression per Response Evaluation Criteria in Solid Tumors (RECIST), whichever occurs first. The percentage of extracranial progression at first progression within 12 and 24 months after starting protocol treatment will be estimated as number of patients who experience the first progression which is extracranial progression divided by number of patients who are still at risk up to 12 and 24 months, respectively.

    9. Overall survival [ Time Frame: From the first day of study treatment to death due to any cause, assessed up to 5 years ]
      Overall survival is defined as the time from the first day of study treatment to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. No formal comparison will be made among the cohorts.

    10. Incidence of adverse events [ Time Frame: Up to 5 years ]
      Assessed per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, toxicity is defined as adverse events that are classified as possibly, probably, or definitely related to study treatment. Toxicities will be evaluated via the ordinal CTCAE standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by patient and treatment cohort will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of the analysis. No formal comparison will be made among the cohorts.

    TRIAL NUMBER: CG01 GBM

    Title: Standard Chemotherapy versus Chemotherapy Chosen by Cancer Stem Cell Chemosensitivity Testing in the Management of Patients with Recurrent Glioblastoma Multiforme (GBM)

    Purpose:

    The purpose of this clinical study is to confirm the utility of chemosensitivity tumor testing on cancer stem cells (ChemoID) as a predictor of clinical response in poor prognosis malignant brain tumors such as recurrent glioblastoma (GBM).

    This study is designed as a parallel group randomized controlled clinical trial to determine if recurrent Glioblastoma (GBM) patients treated with drugs predicted by the ChemoID assay will have better outcomes than patients treated with standard-of-care control therapy chosen by the Physician.

    Upon obtaining informed consent, all eligible participants affected by recurrent GBM will have a tumor biopsy to undergo ChemoID drug response testing with multiple FDA-approved chemotherapeutic agents.

    Eligible participants will be randomized to a standard treatment arm with control treatment (chemotherapy chosen by the Physician from a provided list), or to a study arm of FDA-approved drugs selected by the ChemoID drug response assay.

    TRIAL NUMBER: N0577

    Title: N0577 (CODEL): Phase III Intergroup Study of Radiotherapy with Concomitant and Adjuvant Temozolomide versus Radiotherapy with Adjuvant PCV Chemotherapy in Patients with 1p/19q Co-deleted Anaplastic Glioma or Low Grade Glioma

    Purpose: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving radiation with concomitant and adjuvant temozolomide versus radiation with adjuvant PCV is more effective in treating anaplastic glioma or low grade glioma.

    TRIAL NUMBER: WF-1801

    Title: A Single Arm, Pilot Study of Ramipril for Preventing Radiation-Induced Cognitive Decline in Glioblastoma (GBM) Patients Receiving Brain Radiotherapy

    Purpose: This study is to determine if an oral drug called Ramipril can lower the chance of memory loss in patients with glioblastoma getting chemoradiation. Patients will take Ramipril during chemoradiation and continue until 4 months post-treatment. Memory loss will be assessed using several neurocognitive tests throughout the duration of the study.

    TRIAL NUMBER: A211601

    Title: EVALUATION OF MAMMOGRAPHIC BREAST DENSITY EFFECT OF ASPIRIN: A COMPANION STUDY TO ALLIANCE STUDY A011502

    Purpose: Primary Outcome Measures : Mammographic percent density (MPD) in the contralateral (unaffected) breast between the aspirin and placebo arms [ Time Frame: At 1 year post-registration to A011502 ] The 1-year mammographic percent density (MPD) in the contralateral (unaffected) breast between the aspirin and placebo arms will be compared. Analysis of covariance (ANCOVA) adjusting for baseline MPD will be used to compare MPD at 1 year between the arms. After adjusting for the baseline MPD, it will be concluded that the 1-year MPD is statistically different between the two arms if the corresponding two-sided p-value is less than 0.05. If normality of the primary variable is questionable, then variable transformation or nonparametric Wilcoxon rank-sum test on simple change MPD values may be considered as alternative approaches. A subsequent exploratory analysis will include all patients with an MPD computed at baseline (regardless of that baseline value) and at 1-year post-baseline.

    Secondary Outcome Measures : Mammographic percent density (MPD) in the contralateral (unaffected) breast between the aspirin and placebo arms [ Time Frame: At 2 years post-registration to A011502 ] The 2-year mammographic breast density in the contralateral (unaffected) breast between the two arms for those patients with a baseline mammographic percent density (MPD) >= 25% and a 2-year post-baseline MPD will be compared. ANCOVA will be used to compare MPD between the arms. The corresponding test for the between-arm difference in MPD at 2-years will also be carried out at the 0.05 significance level.

    TRIAL NUMBER: EA1181

    Title: CompassHER2-pCR: PREOPERATIVE THP AND POSTOPERATIVE HP IN PATIENTS WHO ACHIEVE A PATHOLOGIC COMPLETE RESPONSE PART 1 COMPONENT OF: THE CompassHER2 TRIALS (COMPREHENSIVE USE OF PATHOLOGIC RESPONSE ASSESSMENT TO OPTIMIZE THERAPY IN HER2-POSITIVE BREAST CANCER)

    Purpose:

    Primary Outcome Measures :
    1. Recurrence-free survival (RFS) [ Time Frame: Up to 3 years after end of treatment ]
      Events include recurrence of ipsilateral invasive breast tumor, recurrence of locoregional invasive breast tumor, and distant recurrence. Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and estrogen receptor (ER) status. Greenwood method will be used to estimate the 95% confidence interval for 3-year rate.


    Secondary Outcome Measures :
    1. Invasive disease-free survival (IDFS) [ Time Frame: Up to 3 years after the end of treatment ]
      Events include recurrence of ipsilateral invasive breast tumor, recurrence of locoregional invasive breast tumor, distant recurrence, contralateral invasive breast cancer, and second primary non-breast invasive cancer (other than squamous or basal cell skin cancer). Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

    2. Distant disease-free survival (DDFS) [ Time Frame: Up to 3 years after the end of treatment ]
      Events include distant recurrence and second primary non-breast invasive cancer (other than squamous or basal cell skin cancer). Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

    3. Distant relapse-free survival (DRFS) [ Time Frame: U to 3 years after the end of treatment ]
      Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

    4. Recurrence-free interval (RFI) [ Time Frame: Up to 3 years after the end of treatment ]
      Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

    5. Overall survival (OS) [ Time Frame: From date of surgery until the date of death from any cause, assessed up to 3 years after the end of treatment ]
      Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

    6. Event-free survival (EFS) [ Time Frame: Up to 3 years after the end of treatment ]
      Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

    7. Incidence of adverse events (AEs) [ Time Frame: Up to 1 week after cycle 4 (all patients) and/or up to cycle 13 post-surgery (Arm A only) (each cycle is 21 days) ]
      Will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. All treatment-emergent and baseline adverse events and hematological/biochemical toxicities based on laboratory measurements, as well as drug related AEs, will be summarized by NCI CTCAE v5.0 worst grade. The incidence of deaths and treatment-emergent serious adverse events (defined as number of patients experiencing the AE divided by all treated patients) will be summarized using binominal proportions and binomial exact 95% confidence intervals. The incidence of adverse events leading to discontinuation of protocol therapy will be summarized and listed as well.

    TRIAL NUMBER: NRG-BR004

    Title: A Randomized, Double-Blind, Phase III Trial of Paclitaxel/Trastuzumab/Pertuzumab With Atezolizumab or Placebo in First-Line HER2-Positive Metastatic Breast Cancer

    Purpose: his randomized phase III trial studies how well paclitaxel, trastuzumab, and pertuzumab with or without atezolizumab works in treating patients with breast cancer that has spread to other parts of the body. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as trastuzumab, pertuzumab, and atezolizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving paclitaxel, trastuzumab, and pertuzumab with or without atezolizumab may kill more tumor cells.

    TRIAL NUMBER: S1703

    Title: S1703; Randomized Non-Inferiority Trial Comparing Overall Survival of Patients Monitored with Serum Tumor Marker Directed Disease Monitoring (STMDDM) versus Usual Care in Patients with Metastatic Hormone Receptor Positive Breast Cancer

    Purpose: To assess whether patients with HER-2 negative, hormone receptor positive, metastatic breast cancer who are monitored with serum tumor marker directed disease monitoring (STMDDM) have non-inferior overall survival compared to patients monitored with usual care.

    TRIAL NUMBER: S1706

    Title: A PHASE II RANDOMIZED TRIAL OF OLAPARIB (NSC-747856) ADMINISTERED CONCURRENTLY WITH RADIOTHERAPY VERSUS RADIOTHERAPY ALONE FOR INFLAMMATORY BREAST CANCER

    Purpose: Primary Outcome Measures : Invasive Disease-Free Survival (IDFS) [ Time Frame: Up to 8 years ] Time from date of registration to date of first invasive recurrence (local, regional or distant), second invasive primary cancer (breast or not), or death due to any cause. Patients last known to be alive who have not experienced recurrence or second primary cancer are censored at their last contact date. Analysis will be on an intent-to-treat basis and will estimate the survival endpoints using the product-limit method of Kaplan and Meier and will compare the time-to-event distributions using log-rank test statistics. Hazard ratios will be calculated from Cox regression analyses. Effect modification by the stratification variables will be tested as interactions with treatment and separate hazard ratios with 95% confidence intervals by major subgroups will be displayed in a forest plot to examine for consistency of the treatment effect over these subgroups. Secondary Outcome Measures : Locoregional Recurrence-Free Interval (Local Disease-Free Interval (LDFI)) [ Time Frame: Up to 8 years ] Time from date of registration to date of invasive local or regional recurrence. Patients last known to be alive without recurrence are censored at their last contact date. Patients with distant recurrence, second primary cancer or death are censored at the time of that event. A competing risk framework will be conducted separating out the event types of locoregional recurrence from distant recurrence and death. Hazard ratios will be calculated from Cox regression analyses. Effect modification by the stratification variables will be tested as interactions with treatment and separate hazard ratios with 95% confidence intervals by major subgroups will be displayed in a forest plot to examine for consistency of the treatment effect over these subgroups. Distant Relapse-Free Survival (Distant Recurrence-Free Survival) [ Time Frame: Up to 8 years ] Time from date of registration to date of invasive distant disease recurrence, second invasive primary cancer (breast or not) or death due to any cause. Patients last known to be alive who have not experienced disease recurrence, or second primary cancer are censored at their last contact date. Overall Survival [ Time Frame: Up to 8 years ] Time from date of registration to date of death due to any cause. Patients last known to be alive are censored at their last contact date.

    TRIAL NUMBER: WF 97116

    Title: Phase 3 Randomized Placebo Controlled Clinical Trial of Donepezil - WF 97116

    Purpose: This study is to compare the safety and effects of donepezil (Aricept) or if it decreases memory loss after receiving chemotherapy for breast cancer.

    TRIAL NUMBER: DCP-001

    Title: DCP-001, Use of a Clinical Trial Screening Tool to Address Cancer Health Disparities in the NCI Community Oncology Research Program (NCORP)

    Purpose: The protocol is not a scientific study; rather, a method to implement the screening tool and allow the collection and analyses of expanded data with informed consent. Investigators also enroll patients into NCI-treatment trials. The tool, based on a screening log successfully used within the NCI Community Cancer Centers Program (NCCCP), has been streamlined and integrated into the sites’ workflow by using OPEN. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. Also missing from the existing data is the context of care, within the communities themselves where most cancer and at risk of cancer patients receive care which is the focus of NCORP. The profile of patients accrued to NCI-sponsored clinical trials lacks both racial/ethnic and socioeconomic diversity. Accrued patients tend to be insured, highly educated and of higher socioeconomic means. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. NCORP's clinical trials portfolio includes cancer control, prevention, screening, symptom science, and cancer care delivery research.

    TRIAL NUMBER: DCP-002

    Title: DCP-002 Early Onset Malignancies Initiative (EOMI): Molecular profiling of Breast, Prostate, Colorectal, Liver, Kidney, and Multiple Myeloma among Racially and Ethnically Diverse Populations

    Purpose: The primary objective of the EOMI (Early Onset Malignancy Initiative) is to acquire tissue and blood, and other biospecimens for research purposes from tests performed for clinical care or for research indications on other research protocols to accelerate our understanding of the molecular basis of early onset cancers occurring in racial and/or ethnic minority populations through the application of genome analysis technologies, including large-scale genome sequencing and clinical data analysis.

    TRIAL NUMBER: EA2165

    Title: Nivolumab After Combined Modality Therapy in Treating Patients With High Risk Stage II-IIIB Anal Cancer

    Purpose: This randomized phase II clinical trial studies how well nivolumab after combined modality therapy works in treating patients with high risk stage II-IIIB anal cancer. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

    TRIAL NUMBER: S1823

    Title: A PROSPECTIVE OBSERVATIONAL COHORT STUDY TO ASSESS miRNA 371 FOR OUTCOME PREDICTION IN PATIENTS WITH NEWLY DIAGNOSED GERM CELL TUMORS

    Purpose:

    Primary Outcome Measures :
    1. Relapse rate of active germ cell malignancy for those undergoing active surveillance of clinical stage I (CSI)/stage IIA germ cell malignancy [ Time Frame: Up to 3 years ]
    2. Positive predictive value [ Time Frame: Up to 3 years ]

    Biospecimen Retention:   Samples With DNA
    Blood

    TRIAL NUMBER: NRG GU005

    Title: Phase III IGRT and SBRT Vs IGRT and Hypofractionated IMRT for Localized Intermediate Risk Prostate Cancer

    Purpose: 1. OBJECTIVES 1.1 Primary Objectives ? To determine whether SBRT can be shown to be superior to hypofractionated IMRT in terms of GU and GI toxicity by having fewer patients that experience a minimal important decline (MID) in urinary irritation/obstructive and bowel HRQOL as measured by EPIC-26 at 24 months post completion of therapy. ? To determine if SBRT (5 fractions of 7.25 Gy) is superior to hypofractionated IMRT (28 fractions of 2.5 Gy) as measured by Disease Free Survival (DFS) 1.2 Secondary Objectives ? Secondary ObjectivesTo determine whether SBRT can be shown to be superior to hypofractionated IMRT at 12 and 24 months post completion of therapy in terms of HRQOL by having fewer patients that experience a minimal important decline (MID) bowel (12 months only) sexual, hormonal, urinary irritation/obstructive (12 months only) and in urinary incontinence HRQOL as measured by EPIC-26 ? To determine if SBRT (5 fractions of 7.25 Gy) is superior to hypofractionated IMRT (28 fractions of 2.5 Gy) as measured by biochemical failure, overall survival, local failure, prostate cancer specific survival, and distant metastases ? To determine the correspondence between the diagnostic MRI and biopsy 1.3 Exploratory Objectives ? To determine whether a potentially more expensive therapy, SBRT, would be cost-effective than standard hypofractionated IMRT as measured by the EQ-5D-5L ? To explore the relationship between PIRADSv2 grade with biochemical failure ? Collect specimens for future translational research analyses

    TRIAL NUMBER: GOG 0263

    Title: RANDOMIZED PHASE III CLINICAL TRIAL OF ADJUVANT RADIATION VERSUS CHEMORADIATION IN INTERMEDIATE RISK, STAGE I/IIA CERVICAL CANCER TREATED WITH INITIAL RADICAL HYSTERECTOMY AND PELVIC LYMPHADENECTOMY

    Purpose: PRIMARY OBJECTIVES:
    I. To determine if post-operative adjuvant chemoradiotherapy (CRT) can significantly improve recurrence-free survival (RFS) when compared to radiation therapy (RT) alone in patients with intermediate- risk factors stage I- IIA cervical cancer after treatment with radical hysterectomy.
    SECONDARY OBJECTIVES:
    I. To compare the overall survival (OS) of patients treated with these regimens.
    II. To assess differences in incidence and severity of regimen-attributed adverse events in these patients.
    III. To provide assessment of patient risk vs benefit (positive study only). IV. To determine whether post-operative adjuvant CRT improves the health- related quality-of-life compared to RT alone.
    V. To compare toxicity profiles with particular focus on treatment-related genitourinary, gastrointestinal, neurological, pain, and sexual adverse events in these patients.
    TERTIARY OBJECTIVES:
    I. To bank archival tumor tissue for research studies, including studies that evaluate the association between biomarkers, RFS, OS, and clinical-surgical- pathologic characteristics in patients treated with these regimens.
    II. To bank DNA from whole blood for research studies, including studies that evaluate associations between single nucleotide polymorphisms (SNPs), and measures of clinical outcome, including RFS, OS, and adverse events in patients treated with these regimens.
    OUTLINE: This is a multicenter study. Patients are stratified according to capillary-lymphovascular space involvement (positive vs negative), stromal invasion (deep vs middle vs superficial), radiotherapy modality (external- beam radiation therapy [EBRT] vs intensity-modulated radiation therapy [IMRT]), and cooperative group (KGOG vs GOG). Patients are randomized to 1 of 2 treatment arms.
    ARM I: Patients undergo pelvic EBRT or IMRT 5 days a week for 5.5 weeks.
    ARM II: Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in arm I. Treatment with cisplatin repeats every 7 days for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
    Patients complete questionnaires on smoking history, Functional Assessment of Cancer Therapy (FACT-G, Version 4), FACT-Neurotoxicity subscale, and the Brief Pain Inventory (BPI) at baseline and periodically during study.
    Tumor tissue and blood samples may be collected and banked for future biomarker and other analysis.
    After completion of study therapy, patients are followed up every 3 months for 2 years, and then every 6 months for 3 years.

    TRIAL NUMBER: NRG-GY006

    Title: A Randomized Phase II Trial of Radiation Therapy and Cisplatin Alone or in Combination with Intravenous Triapine in Women with Newly Diagnosed Bulky Stage IB2, Stage II, IIIB, or IVA Cancer of the Uterine Cervix or Stage II-IVA Vaginal Cancer

    Purpose: This randomized phase II trial studies radiation therapy and cisplatin with triapine to see how well they work compared to the standard radiation therapy and cisplatin alone in treating patients with newly diagnosed stage IB2, II, or IIIB-IVA cervical cancer or stage II-IVA vaginal cancer. Radiation therapy uses high energy protons to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether radiation therapy and cisplatin are more effective with triapine in treating cervical or vaginal cancer.

    TRIAL NUMBER: NRG-GY019

    Title: A RANDOMIZED PHASE III, TWO-ARM TRIAL OF PACLITAXEL/CARBOPLATIN/MAINTENANCE LETROZOLE VERSUS LETROZOLE MONOTHERAPY IN PATIENTS WITH STAGE II-IV, PRIMARY LOW-GRADE SEROUS CARCINOMA OF THE OVARY OR PERITONEUM

    Purpose:

    Primary Outcome Measures :
    1. Progression-free survival (PFS) [ Time Frame: Time from the randomized treatment assignment to documentation of disease progression (Response Evaluation Criteria in Solid Tumors 1.1) or death from any cause, whichever comes first, assessed up to 8 years ]
      The PFS comparison will be assessed at the second interim and final analyses using a logrank test stratified by country and residual disease status. Estimates for the letrozole/letrozole (L/L) vs paclitaxel/carboplatin/letrozole (CT/L) hazard ratio and its confidence interval will be obtained using a stratified Cox proportional hazards model. Potential confounding factors, including the stratification factors, performance status and self-declared racial designation will be considered in a final exploratory model. A forest plot of treatment hazard ratios with confidence intervals within subgroups will also be reported. PFS will be characterized by treatment group with Kaplan-Meier plots and estimates of the median PFS.


    Secondary Outcome Measures :
    1. Incidence of adverse events (AE) [ Time Frame: Up to 8 years ]
      The nature, frequency and degree of toxicity will be tabulated at the System Organ Class and AE Term levels using Common Terminology Criteria for Adverse Events version 5.0. Each patient will be represented according the maximum grade observed for each term, within randomized treatment assignment. Tabulations will show the number and percentage of patients by maximum grade, within their randomized treatment assignment.

    2. Objective response rate (ORR) [ Time Frame: Up to 8 years ]
      Will be estimated as the binomial proportion of patients with best overall response of complete response (CR) or partial response (PR) among patients with measurable disease after cytoreductive surgery. Response rates and their 95% Wilson-Score confidence intervals will be estimated for each treatment arm, using the randomized treatment assignment. The odds-ratio for ORR in the L/L vs CT/L arms will be estimated from the multivariable logistic regression model adjusted for stratification factors.

    3. Duration of response [ Time Frame: Time from documentation of response under documentation of progression or death, which is observed first, assessed up to 8 years ]
      Will be defined among patients with best overall response of CR or PR. Comparison of response duration between the randomized treatment arms will be supported by Kaplan Meier methods, and the corresponding estimates for median duration and its 95% confidence intervals.

    4. Overall survival (OS) [ Time Frame: Time between randomization and death from any cause, assessed up to 8 years ]
      Differences in OS across the randomized treatment groups will be assessed using Kaplan Meier methods, with median time to death estimates and the corresponding 95% confidence intervals. The L/L vs CT/L hazard ratio will be estimated by a proportional hazards model stratified by the randomization stratification factors.

    5. Adherence to letrozole maintenance therapy [ Time Frame: At cycles 1, 6, and 12 ]
      Will be quantified as the mean rate of adherence (MRA), calculated as the proportion of product not returned divided by the number of days since the previous visit at which study products were dispensed. Currently, the letrozole is delivered in a 2.5 mg pill, and the recommended dose is 2.5 mg per day. This outcome will be computed for each treatment cycle (generally 21 days). The mean MRA will be compared between the randomized treatment groups using linear mixed model methods. The model will be specified with a random patient effect, and fixed effects for randomized treatment indicator, time (cycle number) and the interaction, with an adjustment for the protocol stratification factors. Primary interest is in the difference in mean (MRA) at cycles 1, 6 and 12 between the treatment group. The results will be reported as the estimated mean (MRA) and 95% confidence intervals for each treatment/time combination. Treatment differences within stratification factors may also be considered.

    TRIAL NUMBER: NRG-GY020

    Title: A Phase III Randomized Trial of Radiation +/- MK-3475 (Pembrolizumab) for Newly Diagnosed Early Stage High Intermediate Risk Mismatch Repair Deficient (dMMR) Endometrioid Endometrial Cancer

    Purpose: This phase III trial compares whether the addition of pembrolizumab to radiation therapy is more effective than radiation therapy alone in reducing the risk of cancer coming back (recurrence) in patients with newly diagnosed stage I-II endometrial cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. The addition of pembrolizumab to radiation treatment may be more effective than radiation treatment alone in reducing cancer recurrence.

    TRIAL NUMBER: RTOG-0724

    Title: PHASE III RANDOMIZED STUDY OF CONCURRENT CHEMOTHERAPY AND PELVIC RADIATION THERAPY WITH OR WITHOUT ADJUVANT CHEMOTHERAPY IN HIGH-RISK PATIENTS WITH EARLY-STAGE CERVICAL CARCINOMA FOLLOWING RADICAL HYSTERECTOMY

    Purpose: OBJECTIVES:
    Primary ?To determine if administering adjuvant systemic chemotherapy after chemoradiotherapy will improve disease-free survival compared to chemoradiotherapy alone in patients with high-risk early-stage cervical carcinoma found to have positive nodes and/or positive parametria after radical hysterectomy.
    Secondary ?To evaluate adverse events. ?To evaluate overall survival. ?To evaluate quality of life. ?To evaluate chemotherapy-induced neuropathy. ?To perform a post-hoc dose-volume evaluation between patients treated with standard radiotherapy and patients treated with intensity-modulated radiotherapy (IMRT) with respect to toxicity and local control. ?To collect fixed tissue samples to identify tumor molecular signatures that may be associated with patient outcomes, such as adverse events, disease-free survival, and overall survival. ?To collect blood samples to identify secreted factors from serum and plasma that may be associated with adverse events or outcome and to identify single nucleotide polymorphisms (SNPs) in genes from buffy coat that may be associated with a genetic predisposition to tumor formation itself or a response to cytotoxic therapy.
    OUTLINE: This is a multicenter study. Patients are stratified according to planned use of brachytherapy (no vs. yes), radiotherapy modality - [standard external beam radiotherapy (EBRT) vs. intensity-modulated radiotherapy (IMRT)], and radiotherapy dose (45 Gy vs. 50.4 Gy). Patients are randomized to 1 of 2 treatment arms. ?Arm I: Patients undergo standard EBRT or IMRT to the pelvis once daily 5 days a week for 5-6 weeks. Patients also receive concurrent cisplatin IV over 1 hour once weekly for 6 weeks.
    NOTE: Some patients may also undergo brachytherapy beginning within 7 days after completion of radiotherapy. ?Arm II: Patients receive chemoradiotherapy as in arm I. Beginning 4-6 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
    Quality of life is assessed by the Functional Assessment of Cancer Therapy - Gynecologic Oncology Group (FACT-GOG/NTX4), FACT-Cx, and FACIT-D questionnaires at baseline; at the completion of chemoradiotherapy; and then at 6, 12, and 24 months after completion of chemoradiotherapy.
    Blood and tissue samples may be collected for gene expression analysis by immuno-histochemistry (IHC) and for biomarker and polymorphism studies.
    After completion of study treatment, patients are followed up very 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

    TRIAL NUMBER: EA3132

    Title: EA3132:Phase II Randomized Trial of Radiotherapy with or Without Cisplatin for Surgically Resected Squamous Cell Carcinoma of the Head and Neck (SCCHN) with TP53 Sequencing

    Purpose: This phase II trial studies how well radiation therapy with or without cisplatin works in treating patients with stage III-IVA squamous cell carcinoma of the head and neck who have undergone surgery. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known if radiation therapy is more effective with or without cisplatin in treating patients with squamous cell carcinoma of the head and neck.

    TRIAL NUMBER: NRG-HN004

    Title: Randomized Phase II/III Trial of Radiotherapy with Concurrent MEDI4736 (Durvalumab) vs. Radiotherapy with Concurrent Cetuximab in Patients with Stage III-IVB Head and Neck Cancer with a Contraindication to Cisplatin

    Purpose: PRIMARY OBJECTIVES:
    I. To determine whether radiotherapy (RT) with concurrent and adjuvant anti-PD-L1 therapy (durvalumab) is feasible in patients with locoregionally advanced head and neck cancer (HNC) who have a contraindication to cisplatin. (Lead-in) II. To test the hypothesis that concurrent RT and anti-PD-L1 therapy improves progression free survival (PFS) compared to standard therapy (RT with concurrent cetuximab) in patients with locoregionally advanced HNC who have a contraindication to cisplatin. (Phase II) III. To test the hypothesis that concurrent RT and anti-PD-L1 therapy improves overall survival compared to standard therapy (RT with concurrent cetuximab) in patients with locoregionally advanced HNC who have a contraindication to cisplatin. (Phase III)
    SECONDARY OBJECTIVES:
    I. To compare toxicity between patients treated with RT + anti-PD-L1 therapy versus RT/cetuximab.
    II. To test the effect of anti-PD-L1 therapy in the subpopulation of patients with tumors that overexpress PD-L1.
    III. To compare overall survival, response (at 4-month fludeoxyglucose F-18 [FDG]-positron emission tomography [PET]-computed tomography [CT]), locoregional failure, distant metastasis, and competing mortality in the two arms by known risk factors, including p16 status and omega score.
    IV. To test the hypothesis that durvalumab therapy arm will improved 1 year quality of life (QOL) compared to the cetuximab arm using European Organization for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-core [C]30 version 3.0) / Head-and-Neck module (EORTC QLQ/H&N35) and other quality of life (QOL) tools.
    TERTIARY OBJECTIVES:
    I. To test the hypothesis that radiation combined with durvalumab enhances the adaptive immune response using three types of immunophenotyping compared to radiation combined with cetuximab.
    OUTLINE: Patients are randomized to 1 of 2 arms.
    ARM I: Patients receive cetuximab intravenously (IV) over 120 minutes weekly. Treatment repeats every week for up to 8 courses in the absence of disease progression or unacceptable toxicity. Beginning 5-7 days after first cetuximab dose, patients undergo intensity modulated radiation therapy (IMRT) 5 fractions per week for up to 7 weeks.
    ARM II: Patients receive durvalumab IV over 60 minutes every 4 weeks. Treatment repeats every 4 weeks for up to 7 courses in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients undergo IMRT 5 fractions per week for up to 7 weeks.
    After completion of study treatment, patients are followed up at 1 month, every 4 months for 1 year, every 6 months for 2 years, then annually thereafter.

    TRIAL NUMBER: NRG-HN005

    Title: A RANDOMIZED PHASE II/III TRIAL OF DE-INTENSIFIED RADIATION THERAPY FOR PATIENTS WITH EARLY-STAGE, P16-POSITIVE, NON-SMOKING ASSOCIATED OROPHARYNGEAL CANCER

    Purpose:

    Primary Outcome Measures :
    1. Progression-free survival (PFS) (Phase II) [ Time Frame: Up to 6 years ]
      Will be estimated for all treatment arms using the Kaplan-Meier method (1958). The primary phase IIR endpoint will be tested using a confidence interval (CI) approach.

    2. PFS (Phase III) [ Time Frame: Up to 6 years ]
      Will be estimated for all treatment arms using the Kaplan-Meier method (1958). The co-primary phase III endpoint will be tested using a confidence interval (CI) approach.

    3. Quality of life [ Time Frame: Baseline up to 6 years ]
      Measured by the MD Anderson Dysphagia Inventory (MDADI) global quality of life (QOL) score. Will be compared between arms using a two-sample independent t-test at a one-sided significance level of 0.05 for each experimental arm comparison. MDADI global score and change from baseline will be summarized using mean and standard deviation at each time point for each arm.


    Secondary Outcome Measures :
    1. Locoregional failure [ Time Frame: From the time of randomization to the date of failure, date of precluding event, or last known follow-up date, assessed up to 6 years ]
      The cumulative incidence estimator will be used to estimate time to event distributions for locoregional failure between arm differences tested using cause-specific log-rank test.

    2. Distant failure [ Time Frame: Up to 6 years ]
    3. Overall survival [ Time Frame: From the date of randomization to the date of death or last known follow-up date, with patients alive at the last known follow-up time treated as censored, assessed up to 6 years ]
      Will be estimated using the Kaplan-Meier method and treatment arms compared using the log-rank test (Kaplan 1958).

    4. Incidence of adverse events [ Time Frame: Up to 6 years ]
      Measured by the Common Terminology Criteria for Adverse Events (CTCAE). Adverse events (AEs) will be graded using CTCAE version (v)5.0. Counts of all AEs by grade will be provided by treatment arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm. The number of patients with at least 1 grade 3 or higher AE will be compared between the treatment arms. A comparison between treatment arms of grade 3 and higher AEs related to treatment will also be tested. A comparison of grade 3 and higher events will be compared between treatment arms. All comparisons will be tested using a Chi-Square test, or Fisher's exact test if cell frequencies are < 5, with a significance level of 0.05.

    5. Hearing [ Time Frame: Baseline up to 24 months from end of radiation therapy (RT) ]
      Measured as Hearing Handicap Inventory for Adults-Screening (HHIA-S).

    6. Quality of life [ Time Frame: Baseline up to 24 months from end of RT ]
      Measured by the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire (QLQ)30.

    7. Fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) locoregional control [ Time Frame: Up to 6 years ]
      Will be associated with PFS.

    8. Negative predictive value of post-RT FDG-PET/CT for locoregional control [ Time Frame: At 1 and 2 years ]
      The negative predictive value of FDG-PET/CT for locoregional control will be estimated using binomial proportions and confidence intervals based on normal approximation.

    9. Negative predictive value of post-RT FDG-PET/CT for PFS [ Time Frame: At 1 and 2 years ]
      The negative predictive value of FDG-PET/CT PFS will be estimated using binomial proportions and confidence intervals based on normal approximation.

    10. Incidence of adverse events [ Time Frame: Up to 6 years ]
      Measured using Patient-Reported Outcomes (PRO)-CTCAE. For each symptom, counts and frequencies will be provided for the worst score experienced by the patient by treatment arm. The proportion of patients with scores >= 1 and >= 3 will be compared between groups using a Chi-square test, or Fisher's exact test if cell frequencies are < 5, using a significance level of 0.05. Analysis of changes in patient reported outcomes over time will analyzed by fitting generalized estimating equations (GEE) models using a logit link (dichotomizing the symptom scores as 0 vs. > 1 and 0-2 vs. 3-4) with time of assessment, treatment arm, and treatment-by-time interaction terms in the model.


    Other Outcome Measures:
    1. Quality of life [ Time Frame: Baseline up to 24 months from end of RT ]
      Measured by EuroQol-5 Dimensional- 5 Level (EQ-5D-5L).

    2. Swallowing physiology [ Time Frame: Up to 6 years ]
      Measured by a Modified Barium Swallow (MBS) test. The proportion of aspiration for each arm will be estimated assuming a binomial distribution and between arm comparison will be performed using a Fisher's exact test.

    3. Locoregional control for patients with post-RT FDG-PET/CT [ Time Frame: At 12-14 weeks post-RT ]
      Locoregional control rates will be compared between negative and positive/undetermined patients. Cox proportional hazards models will be used to determine whether there are differences between these two groups, while adjusting for treatment arm and other covariates (cause-specific Cox models for locoregional failure).

    4. PFS for patients with post-RT FDG-PET/CT [ Time Frame: At 12-14 weeks post-RT ]
      PFS rates will be compared between negative and positive/undetermined patients. Cox proportional hazards models will be used to determine whether there are differences between these two groups, while adjusting for treatment arm and other covariates (cause-specific Cox models for locoregional failure).

    TRIAL NUMBER: A031704

    Title: PD-Inhibitor (Nivolumab) and Ipilimumab Followed by Nivolumab Vs. VEGF TKI Cabozantinib with Nivolumab: A Phase III Trial in Metastatic Untreated REnal Cell CancEr [PDIGREE]

    Purpose: This phase III trial studies how well nivolumab and ipilimumab, followed by nivolumab versus cabozantinib and nivolumab, work in treating patients with renal cell cancer that is untreated and has spread to other parts of the body. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cabozantinib, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known how well cabozantinib and nivolumab work in treating patients with untreated renal cell cancer that has spread to other parts of the body.

    TRIAL NUMBER: A171901

    Title: Older Non-Small Cell Lung Cancer Patients (>/= 70 Years of Age) Treated With First-Line MK-3475 (Pembrolizumab)+/- Chemotherapy (Oncologist's/Patient's Choice)

    Purpose: This trial studies the side effects of pembrolizumab with or without chemotherapy in treating patients with stage IV non-small cell lung cancer that has come back (recurrent) and has spread to other places in the body (advanced). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as pemetrexed and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab with or without chemotherapy may shrink the tumor in older patients with non-small cell lung cancer.

    TRIAL NUMBER: EA5163

    Title: EA5163/S1709 INSIGNA : A Randomized, Phase III Study of Firstline Immunotherapy Alone or in Combination with Chemotherapy in Induction/Maintenance or Postprogression in Advanced Nonsquamous Non-Small Cell Lung Cancer (NSCLC) with Immunobiomarker SIGNature-Driven Analysis

    Purpose: Primary Outcome Measures : Overall survival (OS) [ Time Frame: From randomization to death from any cause, assessed up to 5 years post treatment ] OS distributions will be estimated using the Kaplan-Meier method.

    Secondary Outcome Measures : Progression-free survival (PFS) [ Time Frame: From randomization to documented disease progression or death from any cause, assessed up to 5 years post treatment ] PFS distributions will be estimated using the Kaplan-Meier method.
    Best objective response [ Time Frame: Up to 5 years post treatment ] Best objective response will be evaluated via Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
    Incidence of adverse events [ Time Frame: Up to 30 days post treatment ] Toxicities will be reported via the Common Terminology Criteria for Adverse Events (CTCAE) criteria version 5.0. Toxicity rates between arms in the overall population will be compared using Fisher's exact tests with a one-sided type I error rate of 1.25%; multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes.
    PD-L1 positivity [ Time Frame: At baseline ] PD-L1 positivity will be defined as >= 1% Tumor Proportion Score (TPS) for the purpose of enrollment onto the trial. Strongly PD-L1 positive is defined as >= 50% TPS; weakly positive is defined as 1% - 49% TPS.

    TRIAL NUMBER: LungMAP

    Title: LungMAP: A MASTER PROTOCOL TO EVALUATE BIOMARKER-DRIVEN THERAPIES AND IMMUNOTHERAPIES IN PREVIOUSLY-TREATED NON-SMALL CELL LUNG CANCER (Lung-MAP Screening Study)

    Purpose: 1.1 Primary Objective of the Master Protocol (LungMAP) The primary objective of this screening study is to test patient specimens to determine eligibility for participation in the biomarker-driven and non-matched sub-studies included within the Lung-MAP umbrella protocol. 1.2 Secondary Objectives a. Screening Success Rate Objective To evaluate the screen success rate defined as the percentage of screened patients that register for a therapeutic sub-study. Screen success rates will be evaluated for the total screened population and by the subset of patients screened following progression on previous therapy or pre-screened on current therapy. b. Translational Medicine Objectives 1. To evaluate circulating tumor DNA (ctDNA) and compare to the FMI Foundation tissue molecular profiling results in patients who submit a new biopsy for screening. 2. To establish a tissue/blood repository

    TRIAL NUMBER: NRG-LU005

    Title: Limited Stage Small Cell Lung Cancer (LS-SCLC): A Phase II/III Randomized Study of Chemoradiation Versus Chemoradiation Plus Atezolizumab

    Purpose: Primary Outcome Measures :
    Progression-free survival (PFS) (Phase II) [ Time Frame: Time from randomization to any documented progression or death due to any cause, whichever occurs first, assessed up to 5 years ] Progressive disease (PD) will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will compare the distributions of PFS between treatment arms using a one-sided stratified log-rank test in all randomized eligible patients. The rates at various timepoints (e.g., every 6 months after randomization) and medians of PFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95% confidence interval (CI) will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Results from an unstratified analysis will also be provided.
    Overall survival (OS) (Phase III) [ Time Frame: Time from randomization to the date of death due to any cause, assessed up to 5 years ] The primary hypotheses for the phase II and III portions will be evaluated by comparing arm 1 to arm 2 based on PFS (phase II) and OS (phase III) using a stratified log-rank test. Hazard ratios will be estimated using a stratified Cox regression model. Event rates over time will be estimated within each treatment group using the Kaplan-Meier method.

    Secondary Outcome Measures :
    PFS (phase III) [ Time Frame: Time from randomization to any documented progression or death due to any cause, whichever occurs first, assessed up to 5 years ] The primary hypotheses for the phase II and III portions will be evaluated by comparing arm 1 to arm 2 based on PFS (phase II) and OS (phase III) using a stratified log-rank test. Hazard ratios will be estimated using a stratified Cox regression model. Event rates over time will be estimated within each treatment group using the Kaplan-Meier method.
    Incidence of adverse events [ Time Frame: Up to 5 years ] For each patient, the maximum severity reported for both immune mediated and non-immune mediated adverse events will be used in the summaries. Adverse events will be summarized regardless of relationship to protocol treatment as assessed by the investigator. All adverse events, adverse events leading to withdrawal, interruption or modification of protocol treatment, Grade >= 3 adverse events, and serious adverse events will be summarized. Deaths and cause of death will be summarized. The rate of treatment-related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE, v.5.0) will be reported with the frequency and severity (e.g., type, grade, and attribution) by arm, the analysis will be performed at the time of both phase II and phase III (if applicable) primary endpoint analyses. All adverse events will be classified as either immune or non-immune mediated.
    Objective response rate (ORR) [ Time Frame: Up to 5 years ] Will be defined as the proportion of all randomized subjects whose best overall response (BOR) is either a complete response (CR) or partial response (PR) per RECIST 1.1 criteria. ORR will be compared using a two-sided 5% level Cochran-Mantel Haenszel (CMH) test stratified by the same stratification factors used for randomization. An associated odds ratio and 95% CI will be calculated. The ORR and its corresponding 95% exact CI will also be calculated by Clopper-Pearson for each treatment arm. The difference in ORR between the two treatment arms along with the two-sided 95% CI will be estimated using the following CMH method of weighting, adjusting for the stratification factors.
    Local control [ Time Frame: Up to 5 years ] Will be defined as freedom from local progression, in which a failure is defined as intrathoracic tumor progression by RECIST 1.1 criteria. Local control will be analyzed as competing risks data based on cause-specific hazards approaches, where deaths without local failure will be considered as a competing event and analyzed as "censoring" of local failure. The rates at various timepoints (e.g., every 6 months after randomization) and medians of PFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95% CI will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Results from an unstratified analysis will also be provided.
    Distant metastases-free survival (DMFS) [ Time Frame: Time between the date of randomization and the first date of documented distant metastases or death due to any cause, whichever occurs first, assessed up to 5 years ] Will compare the distributions of DMFS between treatment arms using a one-sided stratified log-rank test in all randomized eligible patients. The rates at various timepoints (e.g., every 6 months after randomization) and medians of DMFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95% CI will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Results from an unstratified analysis will also be provided.
    Quality of life (QoL) [ Time Frame: Up to 15 months after the end of the 4th cycle of chemotherapy ] Will be measured by the Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI). Fisher's exact test will be used to compare the proportions of patients experiencing clinically meaningful deterioration (CMD) between the two arms. FACT-TOI deterioration rates and associated 95% confidence interval will be calculated for each treatment group, based on all randomized subjects. Clopper-Pearson method will be used for calculating 95% CI. The deterioration rates of each arm will also be compared using the CMH test, stratified by histology. FACT-TOI at baseline and at each subsequent assessment, as well as their change from baseline will be summarized using descriptive statistics by treatment group as randomized. The scores at baseline and subsequent time points, as well the changes from baseline at each time point for each treatment group will be compared using the two-sample t-test.
    Quality-adjusted survival [ Time Frame: Up to 2 years ] Assessed using score from the 5-level EuroQol 5-dimensional questionnaire (EQ-5D-5L). Defined as the weighted sum of different time episodes added up to a total quality-adjusted life-year. Subjects' overall health state on a visual analog scale (VAS) at each assessment time point will be summarized using descriptive statistics by treatment group, as randomized. Proportion of subjects reporting problems for the five EQ-5D-5L dimensions at each assessment time point will be summarized by level of problem and by treatment group, as randomized. Percentages will be based on number subjects assessed at assessment time point. Subjects' overall health state on a visual analog scale (EQ-VAS) at each assessment time point will be summarized using descriptive statistics by treatment group, as randomized. Proportion of subjects reporting problems for the five EQ-5D dimensions at each assessment time point will be summarized by level of problem and by treatment group, as randomized.
    Level of fatigue [ Time Frame: Up to 2 years ] Will be measured by the Patient-Reported Outcomes Measurement Information System (PROMIS). Baseline and PROMIS at each subsequent assessment, as well as their change from baseline will be summarized using descriptive statistics by treatment group as randomized. The change from baseline to subsequent timepoints may be compared between treatment arms using a t-test, or Wilcoxon test if the data is non-normal.
    Blood based tumor mutational burden (bTMB) and tissue-based tumor mutational burden (tTMB) [ Time Frame: Up to 5 years ] Correlation with clinical outcomes will be done by summarizing the statistical power to detect interaction effects (ratio of hazard ratios) of 0.33 when the marker positive prevalence is 20%, at 2-sided significance level of 0.05.

    Other Outcome Measures:
    Patient-reported symptomatic toxicities [ Time Frame: Up to 15 months after completion of chemoradiation therapy ] Will be measured by Patient Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE). For each symptom and each domain (i.e., frequency, severity, and interference), counts and frequencies will be summarized for the worst score experienced by the patient by treatment arm.

    TRIAL NUMBER: RTOG-1308

    Title: RTOG-1308:PHASE III RANDOMIZED TRIAL COMPARING OVERALL SURVIVAL AFTER PHOTON VERSUS PROTON CHEMORADIOTHERAPY FOR INOPERABLE STAGE II-IIIB NSCLC

    Purpose: This randomized phase III trial studies proton chemoradiotherapy to see how well it works compared to photon chemoradiotherapy in treating patients with stage II-III non-small cell lung cancer that cannot be removed by surgery. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor, such as photon or proton beam radiation therapy, may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as paclitaxel, carboplatin, etoposide, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether proton chemoradiotherapy is more effective than photon chemoradiotherapy in treating non-small cell lung cancer.

    TRIAL NUMBER: S1827

    Title: A RANDOMIZED PHASE III TRIAL OF MRI SURVEILLANCE WITH OR WITHOUT PROPHYLACTIC CRANIAL IRRADIATION (PCI) IN SMALL-CELL LUNG CANCER

    Purpose:

    Primary Outcome Measures :
    1. Overall survival (OS) [ Time Frame: From the date of registration to date of death due to any cause, assessed up to 2 years after randomization ]
      Will evaluate OS with magnetic resonance imaging (MRI) surveillance alone and MRI surveillance combined with prophylactic cranial irradiation (PCI) for the treatment of small cell lung cancer (SCLC).


    Secondary Outcome Measures :
    1. Cognitive failure-free survival (CFFS) [ Time Frame: Baseline to first neurocognitive failure CF or death due to any cause, assessed up to 12 months after randomization ]
      The comparison of CFFS up to 12 months between the arms will be done using a 1-sided 5% level log-rank test.

    2. CFFS rate [ Time Frame: Baseline to first neurocognitive failure CF or death due to any cause, assessed at 90, 180, 270, 360, 540, and 720 days after randomization ]
      There will be a comparison of the CFFS rates between the arms at each of the assessment times and the cumulative incidence of cognitive failure, evaluating death as a competing risk. The CFFS rates at the landmark times will be estimated using the method of Kaplan-Meier and the difference in rates will be evaluated using a 90% confidence interval using Greenwood?s formula.

    3. Cumulative incidence of cognitive failure [ Time Frame: Neurocognitive function test will be assessed at 90, 180, 270, 360, 540, and 720 days after randomization ]
      The cumulative incidence of cognitive failure in the presence of the competing risk of death will be estimated used the method of Fine and Gray.

    4. OS in an "as-treated" analysis [ Time Frame: From the date of registration to date of death due to any cause, assessed up to 2 years after randomization. Patients will be seen at day 90, 180, 270, 360, 540, and 720 ]
      The comparison of OS in the ?as-treated? analysis will be done as described for the primary analysis, however patients will be categorized per treatment received (patients who do not accept their randomized assignment will be analyzed per treatment received). The number of patients not accepting the randomized assignment will also be summarized.

    5. Brain metastases-free survival (BMFS) [ Time Frame: Up to 2 years after randomization. Patients will have MRI on day 90, 180, 270, 360, 540, and 720 ]
      This will be estimated using the method of Kaplan-Meier and comparisons will be done using a log-rank test at the 1-sided 0.05 level. Hazard ratios and associated confidence intervals will be estimated using a Cox Proportional hazards model. Confidence intervals for medians will be estimated using the method of Brookmeyer-Crowley.

    6. Incidence of adverse events [ Time Frame: Up to 2 years after randomization. Patients will be assessed for adverse event after PCI (for patients on PCI + MRI arm) and at month 3 (all patients) ]
      Binary proportions and associated confidence intervals will be estimated.

    TRIAL NUMBER: A051701

    Title: RANDOMIZED PHASE II/III STUDY OF VENETOCLAX (ABT 199) PLUS HEMOIMMUNOTHERAPY FOR MYC/BCL2 DOUBLE-HIT AND DOUBLE EXPRESSING LYMPHOMAS

    Purpose:

    Primary Outcome Measures :
    1. Progression-free survival (PFS) (phase II) [ Time Frame: From randomization date until the earlier of disease progression, or death from any cause, assessed up to 10 years ]
      Will be compared between the experimental and control arms using a stratified log-rank test. If one of the strata has 0 events or there are numerical issues due to the sparseness of the date within strata, an unstratified log-rank test will be used. The Kaplan-Meier method will be used to estimate PFS distributions. One-year PFS estimates, medians, and corresponding hazard ratios will be provided with 95% confidence intervals for each of the double hit lymphoma (DHL) and double expressing lymphoma (DEL) cohorts.

    2. PFS (phase III) [ Time Frame: At 24 months ]
      Will be compared between the experimental and control arms using a Mantel-Haenszel test without a continuity correction. In the event that there is censoring prior to 24 months, a test based on the complementary log-log transformation of Kaplan-Meier estimates will compare PFS at 24 months between experimental and control arms. Two-year PFS estimates, medians, and corresponding hazard ratios will be provided with 95% confidence intervals overall.


    Secondary Outcome Measures :
    1. Overall survival (OS) (phase III) [ Time Frame: From randomization date until death from any cause, assessed up to 10 years ]
      Using a modified intent-to-treat approach, all eligible patients who are centrally confirmed as having a DHL/DEL subtype will be considered evaluable and included in the analysis of the key secondary endpoint in the arm to which they were randomized and under the centrally designated subtype. OS will be compared between the experimental and control arms using a stratified log-rank test. Two-year OS estimates, medians, and corresponding hazard ratios will be provided with 95% confidence intervals overall.

    2. Event-free survival [ Time Frame: From randomization date until the earlier of non-protocol lymphoma therapy, disease progression, or death from any cause, assessed up to 10 years ]
      Will be compared between the experimental and control arms using a log-rank test. Estimated using Kaplan-Meier method by arm and lymphoma subtype.

    3. Response rate [ Time Frame: Up to 1 week after end of cycle 6 ]

      Response will be evaluated using the Lugano criteria for lymphoma response. Best achieved response rate with the intervention will be determined, defined as the number of patients who attain a complete or partial response using positron emission tomography (PET)/computed tomography (CT) out of the total number of evaluable patients who are randomized.

      Response rates will be compared between arms using a chi-square test once all patients on the study have been evaluated for response. Response rates will be estimated by arm and lymphoma subtype with 95% confidence intervals. Logistic regression will be used in a multivariable analysis to identify baseline variables associated with response.


    4. Inconsistency of local and central results for DEL or DHL status [ Time Frame: Until last patient is registered, up to month 57 ]
      Estimated by the number of patients with a local determination of DHL but not central determination of DHL (i.e., positive for DEL or negative for both DHL and DEL) or local determination of DEL but not central determination of DEL (i.e., positive for DHL or negative for both DHL and DEL) divided by the total number of registered patients with adequate material/tissue for central review.

    TRIAL NUMBER: S1801

    Title: A PHASE II RANDOMIZED STUDY OF ADJUVANT VERSUS NEOADJUVANT MK-3475 (PEMBROLIZUMAB) FOR CLINICALLY DETECTABLE STAGE III-IV HIGH RISK MELANOMA

    Purpose: Primary Outcome Measures : Event-free survival (EFS) in patients with high-risk resectable melanoma randomized to neoadjuvant pembrolizumab with patients randomized to adjuvant pembrolizumab [ Time Frame: Date of randomization to date of first progression or death assessed up to 10 years ] We will use exponential-mixture cure models to describe EFS patterns in the arms.

    Secondary Outcome Measures : Overall survival (OS) [ Time Frame: Up to 10 years ] Will be estimated using the Kaplan-Meier method and compared between arms using log-rank tests and Cox regression models.
    Disease control [ Time Frame: At 24 weeks ] Will be estimated using the Kaplan-Meier method and compared between arms using log-rank tests and Cox regression models.
    Local/regional control in the surgical site(s) [ Time Frame: Up to 10 years ] Will be estimated using the Kaplan-Meier method and compared between arms using log-rank tests and Cox regression models.
    Total number of pembrolizumab doses [ Time Frame: Up to 10 years ] Will use Fisher's exact test to compare the number of pembrolizumab doses received by patients on each treatment arm.
    Pathologic response rate [ Time Frame: Up to 10 years ] Will be tabulated for the neoadjuvant arm and exact 95% confidence intervals will be constructed.
    Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 response rate [ Time Frame: Up to 10 years ] Will be tabulated for the neoadjuvant arm and exact 95% confidence intervals will be constructed.
    Immune-related (i)RECIST response rate [ Time Frame: Up to 10 years ] Will be tabulated for the neoadjuvant arm and exact 95% confidence intervals will be constructed.

    TRIAL NUMBER: 10231

    Title: NCORP TISSUE PROCUREMENT PROTOCOL: AN NCI CANCER MOONSHOT(SM) STUDY

    Purpose: Primary Outcome Measures : Obtaining tumor tissue and blood specimens [ Time Frame: Up to 2 years ] Will obtain tumor tissue and blood specimens for biobanking and to store tissues, blood, and nucleic acids for future research, including the study of matched pre and post-treatment tumor biopsies to elucidate mechanisms of resistance. Cases will be grouped according to histology and/or treatment. Secondary Outcome Measures : Tumor tissues storage in the Biopathology Center (BPC) at Nationwide Children?s Hospital (NCH) (Biorepository) [ Time Frame: Up to 2 years ] Genomic analysis [ Time Frame: Up to 2 years ] Will perform genomic studies, including a pan-cancer gene panel, and contribute molecular data to the genomic data commons. Biospecimen Retention: Samples With DNA Blood, tissue

    TRIAL NUMBER: A231601CD

    Title: A231601CD: Improving Surgical Care and Outcomes in Older Cancer Patients Through Implementation of an Efficient Pre-Surgical Toolkit (OPTI-Surg)

    Purpose: This trial studies how well the use of a pre-surgical toolkit (OPTI-Surg) works in improving surgical care and outcomes in older participants with cancer. In many elderly patients, surgery can greatly affect physical condition and the ability to return to pre-surgery levels of physical functioning. Providing pre-surgical recommendations may help improve participants' recovery rate and functioning after surgery.

    TRIAL NUMBER: EAZ171

    Title: Prospective Validation Trial of Taxane Therapy (Docetaxel or Weekly Paclitaxel) and Risk of Chemotherapy-Induced Peripheral Neuropathy in African American Women

    Purpose:

    Primary Outcome Measures :
    1. Validation of a prior germline predictor of paclitaxel-induced peripheral neuropathy (Arm A) [ Time Frame: Baseline ]
      Patients will be coded as having the event as long as grade 2-4 neuropathy based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 occurred at any time during the observation period. Patients without neuropathy or with maximum of grade 1 neuropathy during the whole observation period will be coded as having no event.


    Secondary Outcome Measures :
    1. Grade 2-4 taxane-induced peripheral neuropathy (TIPN) [ Time Frame: Up to 3 years post-registration ]
      Will be based on CTCAE between both Arm A versus (vs.) Arm.

    2. Patient-related outcome (PRO)-based neurotoxicity [ Time Frame: Up to 3 years post-registration ]
      Will be assessed using the Functional Assessment of Cancer Therapy (FACT)/Gynecologic Oncology Group (GOG)-Neurotoxicity (NTX) questionnaire. The FACT/GOG-Ntx neurotoxicity total score will be analyzed as a continuous variable. Linear mixed effect models with random intercept (repeated measures within single patients with unstructured covariance matrices) will be fit to estimate the average difference in FACT/GOG-Ntx neurotoxicity total score between high versus (vs.) low risk genotype groups in the paclitaxel arm. Time and patient and disease characteristics will be included as covariates in the linear mixed effect model. Genotype group-by-time interaction will be tested to see whether the difference between the two genotype groups depends on time. For comparison between arm A and arm B, the FACT/GOG-Ntx neurotoxicity total score change between the baseline and at end of treatment will be compared using two sample t test.

    3. Health-related quality of life (HRQoL) between both arms [ Time Frame: Up to 3 years post-registration ]
      The HRQoL total score will be analyzed as a continuous variable and compared between low and high-risk genotypes groups of the paclitaxel arm, and between the paclitaxel arm and the docetaxel arm groups, using two-sample t tests. Multivariable linear mixed effect models will also be fit to evaluate the time trend of HRQoL and to estimate the average group difference in HRQoL after adjusting for other covariates. Group-by-time interaction will be tested to see whether the difference in HRQoL between groups depends on time.

    4. Physical function between both arms [ Time Frame: Up to 3 years post-registration ]
      Will be measured using the (PROMIS) Physical Function version (v)2.0 Short From 10a. The PROMIS Physical Function T score will be analyzed as a continuous variable, and it will be compared between the two treatment arms (A&B) and for the high risk vs. low risk genotypes (in arm A) using two-sample t tests

    5. Financial toxicity between both arms [ Time Frame: Up to 6 months post-registration ]
      Will be assessed using the Comprehensive Score for Financial Toxicity (COST) scores and compared using a two-sample t tests.

    6. PRO-CTCAE scores of numbness, tingling, and general pain between both arms [ Time Frame: Up to 3 years post-registration ]
      Will present PRO-CTCAE scores for each attribute (frequency, severity and/or interference) separately and compare PRO-CTCAE severity (coded 0-4) with CTCAE grades for the corresponding time period.


    Other Outcome Measures:
    1. Association between Social economic determinants of health and treatment completion [ Time Frame: Baseline ]
      Social determinants of health (zip code, marital status, education, income & insurance status) will be associated with treatment completion per protocol

    2. Social economic determinants of health and FACT-Ntx neurotoxicity scores [ Time Frame: Baseline ]
      Social determinants of health (zip code, marital status, education, income & insurance status) will be associated with FACT-Ntx neurotoxicity scores

    3. Association between social determinants of health and FACT-Ntx HRQoL scores [ Time Frame: Baseline ]
      Social determinants of health (zip code, marital status, education, income & insurance status) will be associated with FACT-Ntx HRQoL scores

    TRIAL NUMBER: NCICOVID

    Title: NCI COVID-19 in Cancer Patients Study (NCCAPS): A Longitudinal Natural History Study

    Purpose: This study collects blood samples, medical information, and medical images from patients who are being treated for cancer and have a positive test for SARS CoV-2, the new coronavirus that causes the disease called COVID-19. Collecting blood samples, medical information, and medical images may help researchers determine how COVID-19 affects the outcomes of patients undergoing cancer treatment and how having cancer affects COVID-19.

    TRIAL NUMBER: S1714

    Title: A PROSPECTIVE OBSERVATIONAL COHORT STUDY TO DEVELOP A PREDICTIVE MODEL OF TAXANE-INDUCED PERIPHERAL NEUROPATHY IN CANCER PATIENTS

    Purpose: 1.1 Primary Objective a. To develop and validate a clinical risk prediction model using clinical factors for the development of peripheral neuropathy in patients receiving taxane-based chemotherapy regimens. 1.2 Secondary Objectives a. To examine patient-reported outcomes (PROs) and objective measures of chemotherapy induced peripheral neuropathy (CIPN) to better define the phenotype of peripheral neuropathy in this patient population. b. To assess the incidence of CIPN within one year in this patient population. c. To identify predictors of treatment dose reductions, delays, and discontinuations associated with CIPN symptoms in this patient population. 1.3 Other Objectives a. To collect serum and plasma samples for future testing for biomarker and mechanistic studies of CIPN.

    TRIAL NUMBER: A151804

    Title: Establishment of a National Biorepository to Advance Studies of Immune-Related Adverse Events

    Purpose: This trial collects research data and samples from patients who experience immunotherapy side effects to store for use in future research studies. Studying research data and samples from patients who experience immunotherapy side effects may help researchers better understand how to predict, prevent, and treat these side effects.

    TRIAL NUMBER: EAA173

    Title: DARATUMUMAB TO ENHANCE THERAPEUTIC EFFECTIVENESS OF REVLIMID IN SMOLDERING MYELOMA (DETER-SMM)

    Purpose: Primary Outcome Measures :
    Overall survival (OS) [ Time Frame: From randomization to death due to any cause, or censored at date last known alive, assessed up to 15 years ] Will be estimated using the Kaplan-Meier (KM) method and compared using a stratified log-rank test. Stratified cox proportional hazards regression will produce a treatment hazard ratio estimate.
    Functional Assessment of Cancer Therapy-General (FACT-G) score [ Time Frame: Baseline to 24 cycles of treatment (each cycle is 28 days) ] A general effect size measure of half standard deviation will be used to establish the minimally important difference. Descriptive statistics (mean, standard deviation [SD], median, range) will be used to evaluate the distribution of levels and changes for the set of health-related quality of life (QOL) evaluations. Levels and changes will also be assessed graphically. Changes from baseline will be analyzed using linear mixed models based on restricted maximum likelihood estimation with covariance matrix maximizing Akaike information criteria. Models with treatment, assessment time, and treatment by assessment time interaction with and without other predictors will be fit. If there is substantial missingness, will analyze the data according to the methods described in Schluchter and Schluchter, Greene and Beck.

    Secondary Outcome Measures :
    Progression-free survival (PFS) [ Time Frame: From randomization until disease progression or death due to any cause, or censored at date of last disease evaluation, assessed up to 15 years ] Will be estimated using the KM method and compared using a stratified log-rank test. Stratified cox proportional hazards regression will produce a treatment hazard ratio estimate.
    Best response on treatment based on International Myeloma Working Group (IMWG) criteria [ Time Frame: At 12 and 24 months ] Response will be tabulated by category. Response rates of very good partial response (VGPR) or better and partial response (PR) or better will be compared using the Fisher's exact test. Ineligible patients are excluded from the analysis and unevaluable patients are counted in the denominator.
    Incidence of adverse events by worst grade and type for treated patients determined using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: Up to 28 days post-treatment ] Will monitor the toxicities experienced by all treated patients. Will compare rates of worst grade 3 or higher non-hematologic treatment-related events using the Fisher's exact test.
    Incidence of grade 3 or higher infusion-related reactions over course 1 determined based on CTCAE [ Time Frame: During cycle 1 of treatment (each cycle is 28 days) ] Will monitor the toxicities experienced by all treated patients. Will compare rates of worst grade 3 or higher non-hematologic treatment-related events using the Fisher's exact test.
    Stem cell (SC) mobilization failure [ Time Frame: After 4 to 6 cycles of treatment (each cycle is 28 days) ] Defined as not collecting a minimum of 5x10^6 CD34 cells per kilogram weight. SC mobilization and type of growth factor support will be summarized overall and by treatment arm with descriptive statistics.
    Early SC mobilization feasibility [ Time Frame: Up to 6 cycles of treatment (each cycle is 28 days) ] Defined as the proportion of patients less than 65 years of age treated for 6 courses who opt for SC mobilization. SC mobilization and type of growth factor support will be summarized overall and by treatment arm with descriptive statistics.
    Type of growth factor support [ Time Frame: During 4 to 6 cycles of treatment (each cycle is 28 days) ] SC mobilization and type of growth factor support will be summarized overall and by treatment arm with descriptive statistics.
    Change in FACT-G score [ Time Frame: From treatment end to 6 months post-treatment ] A general effect size measure of half standard deviation will be used to establish the minimally important difference. Descriptive statistics (mean, SD, median, range) will be used to evaluate the distribution of levels and changes for the set of health-related QOL evaluations. Levels and changes will also be assessed graphically. Changes from baseline will be analyzed using linear mixed models based on restricted maximum likelihood estimation with covariance matrix maximizing Akaike information criteria. Models with treatment, assessment time, and treatment by assessment time interaction with and without other predictors will be fit. If there is substantial missingness, will analyze the data according to the methods described in Schluchter and Schluchter, Greene and Beck.
    Levels of FACT-G score at each assessment time point [ Time Frame: From baseline, at 3, f7, 13, 19 cycles of treatment, and early discontinuation of treatment, assessed up to 24 cycles of treatment (each cycle is 28 days) ] A general effect size measure of half standard deviation will be used to establish the minimally important difference. Descriptive statistics (mean, SD, median, range) will be used to evaluate the distribution of levels and changes for the set of health-related QOL evaluations. Levels and changes will also be assessed graphically. Changes from baseline will be analyzed using linear mixed models based on restricted maximum likelihood estimation with covariance matrix maximizing Akaike information criteria. Models with treatment, assessment time, and treatment by assessment time interaction with and without other predictors will be fit. If there is substantial missingness, will analyze the data according to the methods described in Schluchter and Schluchter, Greene and Beck.
    Time to worsening of FACT-G [ Time Frame: From baseline until a decrease of 9 points, or censored at date of last assessment, assessed up to 6 months post-treatment ] Will be analyzed with Kaplan-Meier methods and Cox regression with the related treatment arm as the only factor. Correlation between time to worsening of symptoms with PFS and OS will be assessed with Kendall's Tau adjusted for censored observations.

    Other Outcome Measures:
    Cumulative dose calculated as the sum of all doses taken across all cycles [ Time Frame: Up to 24 months ] Cumulative dose will be calculated overall and by cycle. Data will be summarized by treatment arm with descriptive statistics and graphically over time. Patients will be classified into dichotomous groups based on a 75% relative dose intensity cutoff (< 75% versus [vs] >= 75% represents poor vs good treatment adherence). The proportion of patients with poor lenalidomide treatment adherence will be compared between arms using the Fisher's exact test. In addition, multi-variable logistic regression analysis will be conducted to identify the baseline factors associated with calculated good treatment adherence.
    Dose intensity calculated as cumulative dose received divided by treatment duration [ Time Frame: Up to 24 months ] Dose intensity will be calculated overall and by cycle. Data will be summarized by treatment arm with descriptive statistics and graphically over time. Patients will be classified into dichotomous groups based on a 75% relative dose intensity cutoff (< 75% vs >= 75% represents poor vs good treatment adherence). The proportion of patients with poor lenalidomide treatment adherence will be compared between arms using the Fisher's exact test. In addition, multi-variable logistic regression analysis will be conducted to identify the baseline factors associated with calculated good treatment adherence.
    Relative dose intensity calculated as the dose intensity divided by planned dose intensity [ Time Frame: Up to 24 months ] Dose intensity will be calculated overall and by cycle. Data will be summarized by treatment arm with descriptive statistics and graphically over time. Patients will be classified into dichotomous groups based on a 75% relative dose intensity cutoff (< 75% vs >= 75% represents poor vs good treatment adherence). The proportion of patients with poor lenalidomide treatment adherence will be compared between arms using the Fisher's exact test. In addition, multi-variable logistic regression analysis will be conducted to identify the baseline factors associated with calculated good treatment adherence.
    Duration of treatment [ Time Frame: From randomization to date off treatment, or censored at the date of last treatment, assessed up to 24 months ] Treatment duration in each arm will be estimated using Kaplan-Meier methods and compared between arms with the log-rank test.
    Time to progression [ Time Frame: From randomization to progression, or censored at date of last disease evaluation, assessed up to 15 years ] Will be estimated using the Kaplan-Meier method.
    Presence, frequency, interference, amount and/or severity of select patient reported outcomes (PRO)-CTCAEs [ Time Frame: Assessed at each treatment cycle, from cycle 1 of treatment to end of treatment, up to 24 cycles of treatment (each cycle is 28 days) ] Descriptive statistics (mean, standard deviation, median, range) will be used to summarize selected PRO-CTCAEs tabulated at each cycle overall and by arm. Will map PRO-CTCAEs with provider reported adverse events (AEs) and evaluate differences in incidence and worst severity. Items correspond to 5 attributes measured [frequency (F), severity (S), interference (I), presence/absence (P) and amount (A)] based on multiple choice questions. Response for each attribute except P which is binary is on a 5-point Likert scale with 5 indicating 'almost constantly' frequency, 'very severe' severity, 'very much' amount or 'very much' interference. An overall PRO-CTCAE score will be calculated at each time point.
    Overall PRO-CTCAE score [ Time Frame: Up to 15 years ] Defined as the sum of item scores on all symptomatic adverse events (AEs). Descriptive statistics will be used to summarize selected PRO-CTCAEs tabulated at each cycle overall and by arm. Will map PRO-CTCAEs with provider reported AEs and evaluate differences in incidence and worst severity. An overall PRO-CTCAE score will be calculated at each time point.
    Adherence Starts with Knowledge (ASK)-12 scores [ Time Frame: At 7, 13, and 19 cycles of treatment (each cycle is 28 days) ] Descriptive statistics will be used to summarize ASK-12 scores tabulated at cycles 7, 13 and 19 overall and by arm. Differences between arms will be evaluated based a t-test (or Wilcoxon rank sum test). Patients will also be classified into high versus low likelihood of medication adherence groups according to tertile distributions (lowest tertile vs second and top). Association between likelihood of medication adherence and calculated treatment adherence dichotomous groups will be evaluated in patients with both ASK-12 and treatment data at cycles 7, 13 and 19 post randomization. In addition, multivariable logistic regression analysis will be conducted to identify the baseline factors associated with low likelihood of medication adherence.
    PRO compliance rate [ Time Frame: Up to 15 years ] Defined as the proportion of patients who submit the given PRO instrument among those eligible at each time point which excludes those missing by design (due to death or disease progression, early treatment discontinuation).
    PRO completion rate [ Time Frame: Up to 15 years ] Defined as the proportion of patients who complete given PRO instrument based on the instrument's scoring system among those eligible at each time point.

    TRIAL NUMBER: S1803

    Title: S1803; Phase III Study of Daratumumab/rHuPH20 (NSC- 810307) + Lenalidomide or Lenalidomide as Post-Autologous Stem Cell Transplant Maintenance Therapy in Patients with Multiple Myeloma (MM) Using Minimal Residual Disease to Direct Therapy Duration (DRAMMATIC Study)

    Purpose: Patients are enrolled to screening (Reg Step 1) prior to or after ASCT but prior to Reg Step 2. Patients are followed until they will begin Maintenance and then registered to Reg Step 2 (first randomization). Patients are randomized between Lenalidomide for 2 years and Lenalidomide + Daratumumab/rHuPH20. After 2 years of Maintenance, MRD is assessed to guide further therapy. MRD-positive patients will continue with the assigned treatment. MRD-negative patients will be further randomized (Reg Step 3) to either continue or discontinue the assigned treatment. Patients are treated for up to 7 years from Step 2 reg and followed for up to 15 years.

    TRIAL NUMBER: COVID-19 Biospecimen

    Title: COVID-19 Biospecimen Collection

    Purpose:

    TRIAL NUMBER: EA8171

    Title: EA8171:Multiparametric MRI (mpMRI) for Preoperative Staging and Treatment Planning for Newly-Diagnosed Prostate Cancer

    Purpose: This phase II trial studies how well multiparametric magnetic resonance imaging (MRI) works in evaluating cancer stage and helping treatment planning in patients with prostate cancer. Multiparametric MRI may be useful for evaluating the type of cancer in finding aggressive disease.

    TRIAL NUMBER: NRG-GU002

    Title: NRG-GU002: PHASE II-III TRIAL OF ADJUVANT RADIOTHERAPY AND ANDROGEN DEPRIVATION FOLLOWING RADICAL PROSTATECTOMY WITH OR WITHOUT ADJUVANT DOCETAXEL

    Purpose: This randomized phase II/III trial studies docetaxel, antiandrogen therapy, and radiation therapy to see how well it works compared with antiandrogen therapy and radiation therapy alone in treating patients with prostate cancer that has been removed by surgery. Androgen can cause the growth of prostate cells. Antihormone therapy may lessen the amount of androgen made by the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving antiandrogen therapy and radiation therapy with or without docetaxel after surgery may kill any remaining tumor cells.

    TRIAL NUMBER: NRG-GU008

    Title: RANDOMIZED PHASE III TRIAL INCORPORATING ABIRATERONE ACETATE WITH PREDNISONE AND APALUTAMIDE AND ADVANCED IMAGING INTO SALVAGE TREATMENT FOR PATIENTS WITH NODE-POSITIVE PROSTATE CANCER AFTER RADICAL PROSTATECTOMY

    Purpose:

    TRIAL NUMBER: S1802

    Title: S1802: Phase III Randomized Trial of Standard Systemic Therapy (SST) versus Standard Systemic Therapy plus Definitive treatment (surgery or radiation) of the primary tumor in Metastatic Prostate Cancer

    Purpose: This phase III trial studies how well standard systemic therapy with or without definitive treatment (prostate removal surgery or radiation therapy) works in treating participants with prostate cancer that has spread to other places in the body. Addition of prostate removal surgery or radiation therapy to standard systemic therapy for prostate cancer may lower the chance of the cancer growing or spreading.

    TRIAL NUMBER: A031801

    Title: A PHASE II RANDOMIZED TRIAL OF RADIUM-223 DICHLORIDE AND CABOZANTINIB IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA WITH BONE METASTASIS (RADICAL)

    Purpose:

    Primary Outcome Measures :
    1. Symptomatic skeletal event (SSE)-free survival (FS) [ Time Frame: From the date of randomization to the date of the earliest occurrence of SSE or death from any cause, assessed up to 5 years ]
      SSE-FS distribution will be estimated using the method of Kaplan-Meier by treatment arm. Comparison between the two arms will be performed using a one-sided log-rank test and one-sided p-value less than 0.025 will indicate that the experimental arm is superior to the control arm. SSE-FS will be censored at the date of last SSE assessment for those alive and SSE free. Hazard ratio (experimental over control arm) as well as two-sided 90% confidence interval (CI) for treatment will be estimated using the stratified Cox proportional hazard model with a single treatment covariate.


    Secondary Outcome Measures :
    1. Incidence of adverse events [ Time Frame: Up to 5 years ]
      Will be determined using Common Terminology Criteria for Adverse Events version 5.0. Adverse events will be summarized and compared between arms using chi-square or fisher exact tests as appropriate.

    2. SSE-FS [ Time Frame: From randomization to the date of SSE or death due to any cause, whichever comes first, assessed up to 5 years ]
      Will be estimated with the Kaplan Meier methodology. Comparison between arms or between predefined groups will be conducted using the log-rank test.

    3. Progression-free survival [ Time Frame: From randomization to time of radiographic progression or death due to any cause, whichever occurs first, assessed up to 5 years ]
      Radiographic progression will be defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Will be estimated with the Kaplan Meier methodology. Comparison between arms or between predefined groups will be conducted using the log-rank test.

    4. Overall survival [ Time Frame: From randomization to the date of death due to any cause, assessed up to 5 years ]
      Will be estimated with the Kaplan Meier methodology. Comparison between arms or between predefined groups will be conducted using the log-rank test. Patients who are alive will be censored at last follow up date.

    5. Time to first SSE [ Time Frame: From randomization to the date of first SSE or death due to any cause, assessed up to 5 years ]
      Will be determined in each treatment. The median estimate to first SSE-FS will be calculated.

    6. Overall response rate (ORR) [ Time Frame: Up to 5 years ]
      Will be defined by RECIST version 1.1. Number and proportion of patients achieving ORR (by RECIST) will be summarized with two-sided 90% CI by treatment arm; comparison between arms will be conducted using chi-square or Fisher's exact test as appropriate.

    TRIAL NUMBER: S1931

    Title: Phase III Trial of Immunotherapy-Based Combination Therapy With or Without Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma (PROBE Trial)

    Purpose: This phase III trial compares the effect of adding surgery to a standard of care immunotherapy-based drug combination versus a standard of care immunotherapy-based drug combination alone in treating patients with kidney cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, pembrolizumab, and avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Surgery to remove the kidney, called a nephrectomy, is also considered standard of care; however, doctors who treat kidney cancer do not agree on its benefits. It is not yet known if the addition of surgery to an immunotherapy-based drug combination works better than an immunotherapy-based drug combination alone in treating patients with kidney cancer.

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    TRIAL NUMBER: EA2176

    Title: A Randomized Phase III Study of Immune Checkpoint Inhibition with Chemotherapy in Treatment-Naïve Metastatic Anal Cancer Patients

    Purpose:

    Primary Outcome Measures :
    1. Progression-free survival [ Time Frame: Up to 2 years ]
      Defined as the first of progressive disease or death due to any cause. Analyzed using a stratified two-sided overall 0.05 level log-rank test. Will utilize standard Eastern Cooperative Oncology Group -American College of Radiology Imaging Network interim monitoring for efficacy evaluation.


    Secondary Outcome Measures :
    1. Objective response rate (ORR) [ Time Frame: Up to 2 years ]
      ORR is the ratio of the number of patients with a complete response or partial response, as defined by Response Evaluation Criteria in Solid Tumors version 1.1, to the total number of treated patients.

    2. Overall survival [ Time Frame: Time between treatment randomization and death by any cause, assessed up to 2 years ]
      Evaluated by a stratified log-rank test, and using a two-sided 0.05 level Cochran Mantel-Haenzel.

    3. Incidence of adverse events [ Time Frame: Up to 2 years ]
      Analyses of toxicity will be via frequency tabulations and percentages by worst degree of toxicity and comparisons will be done via chi-square or Fisher's exact tests as appropriate.

    TRIAL NUMBER: A031803

    Title: PHASE II TRIAL OF INTRAVESICAL GEMCITABINE AND MK-3475 (PEMBROLIZUMAB) IN THE TREATMENT OF PATIENTS WITH BCG- NRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER

    Purpose:

    Primary Outcome Measures :
    1. Complete response rate in the carcinoma in situ (CIS) subpopulation [ Time Frame: At 6 months ]
      A complete response, only for patients with a CIS component, is a cystoscopy without evidence of bladder tumor, negative biopsy (including directed biopsies to any suspicious areas and in addition random bladder biopsies including trigone, left lateral wall, right lateral wall, posterior bladder, dome of bladder, and the prostatic urethra in men) and negative cytology for high grade disease at 6 months (end of cycle 8, week 25).

    2. Event-free survival at 18 months [ Time Frame: From the date of study registration to the first documentation of an event or death whichever comes first, assessed up to 18 months ]
      EFS will be measure from the date of study registration to the first documentation of an event or death whichever comes first. For patients without a documented event and who are still alive, they will be censored at last disease assessment. For patients who start any subsequent ant-cancer therapy without any reported events will be censored at their last disease assessment. will be obtained with a Kaplan-Meier estimator (using the Greenwood formula to estimate the variance) for the entire 155 patient group consisting of patients with CIS, CIS with Ta/T1 or Ta or T1 disease. A 90% confidence interval will be generated for the 18-month EFS estimate.


    Secondary Outcome Measures :
    1. Incidence of adverse events [ Time Frame: Up to 5 years post treatment ]
      Adverse events will be assessed based on the National Cancer Institute (NCI) common toxicity criteria (Common Terminology Criteria for Adverse Events [CTACAE] version [v] 5.0).

    2. Duration of response (DOR) [ Time Frame: From the time a patient had a documented response that had been confirmed (the time would start at the time a response was first noted) until disease-progression, assessed up to 5 years ]
      Analysis will only include those patients with a confirmed response. Patients who are alive and without a documented progression at the time of analysis will be censored at the time of the last disease status evaluation. The Kaplan-Meier product-limit estimator will be used to estimate DOR, medians and 95% confidence intervals (CI).

    3. Progression-free survival (PFS) [ Time Frame: From the date of study registration to the date of progression or death due to any cause, whichever occurs first, assessed up to 5 years ]
      Surviving patients without any documented progressions will be censored at the date of last known contact. Progression will be defined as the development of muscle invasive bladder cancer or metastatic urothelial cancer (nodal and/or distant). The Kaplan-Meier product-limit estimator will be used to estimate PFS, medians and 95% CI.

    4. Overall survival (OS) [ Time Frame: From the date of study registration to date of death due to any cause, assessed up to 5 years ]
      Surviving patients will be censored at the date of last known contact. The Kaplan-Meier product-limit estimator will be used to estimate OS, medians and 95% CI.

    5. Cystectomy-free survival [ Time Frame: From the date of study registration to the date of cystectomy for all patients ]
      The Kaplan-Meier product-limit estimator will be used to estimate cystectomy-free survival, medians and 95% CI.

    6. Recurrence free survival (RFS) [ Time Frame: From the date of study registration to the first documentation of recurrence or death due to any cause, assessed up to 5 years ]
      Surviving patients without any documented recurrence will be censored at the date of last known contact. Recurrence will be defined as the development of high-grade bladder cancer for patients with a CIS component only and those without a CIS component. The Kaplan-Meier product-limit estimator will be used to estimate RFS, medians and 95% CI.

    TRIAL NUMBER: EA8185

    Title: Phase 2 Study of Bladder-SparIng ChemoradiatioN with MEDI4736 (Durvalumab) in clinical Stage 3, Node PosItive bladdeR cancEr (INSPIRE)

    Purpose:

    Primary Outcome Measures :
    1. Clinical complete response (CR) [ Time Frame: Up to 6 years ]

    Secondary Outcome Measures :
    1. Metastasis-free survival [ Time Frame: From randomization to first evidence of metastatic disease or death from any cause, assessed up to 6 years ]
      Will be estimated by the Kaplan-Meier method.

    2. Bladder-intact event-free survival (BI-EFS) [ Time Frame: From randomization to the first BI-EFS event, assessed up to 6 years ]
      Will be estimated by the Kaplan-Meier method.

    3. Bladder cancer specific survival [ Time Frame: From randomization to death from bladder cancer, assessed up to 6 years ]
      Will be estimated by the Kaplan-Meier method.

    4. Overall survival [ Time Frame: From randomization to death from any cause, assessed up to 6 years ]
      Will be estimated by the Kaplan-Meier method.

    5. Progression-free survival [ Time Frame: From randomization to first of local progression, nodal or distant metastasis, or death from any cause, assessed up to 6 years ]
      Will be estimated by the Kaplan-Meier method.

    6. Complete response duration [ Time Frame: From the date of the biopsy documenting the complete response to the time of muscle invasive recurrence, local progression, evidence of metastatic disease or death due to any cause, assessed up to 6 years ]
      Stratified Cox proportional hazards models will be used to estimate hazard ratios in all eligible patients.

    7. Salvage cystectomy rate [ Time Frame: Up to 6 years ]
      Rate will be reported as a proportion of patients who do not experience clinical benefit after chemoradiotherapy (chemoRT) +/- MEDI4736 (durvalumab) along with a 90% confidence interval. Stratified Cox proportional hazards models will be used to estimate hazard ratios in all eligible patients.

    8. Incidence of adverse events [ Time Frame: Up to 1 year ]
      Assessed using the Common Terminology Criteria for Adverse Events (CTCAE). Toxicity will be evaluated in all treated patients, regardless of eligibility.

    TRIAL NUMBER: S1600

    Title: A Randomized Phase III Double-Blind Clinical Trial Evaluating the Effect of Immune-Enhancing Nutrition on Radical Cystectomy Outcomes

    Purpose: This randomized phase III trial studies how well nutrition therapy works in improving immune system in patients with bladder cancer that can be removed by surgery. Improving nutrition before and after surgery may reduce the infections and other problems that sometimes occur after surgery.

    TRIAL NUMBER: S1806

    Title: S1806: Phase III Randomized Trial of Concurrent Chemoradiotherapy with or Without Atezolizumab in Localized Muscle Invasive Bladder Cancer

    Purpose: This phase III trial studies how well chemotherapy and radiation therapy work with or without atezolizumab in treating patients with localized muscle invasive bladder cancer. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as gemcitabine, cisplatin, fluorouracil and mitomycin-C, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with radiation therapy may kill more tumor cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving atezolizumab with radiation therapy and chemotherapy may work better in treating patients with localized muscle invasive bladder cancer compared to radiation therapy and chemotherapy without atezolizumab.

    TRIAL NUMBER: A071701

    Title: Genomically-Guided Treatment Trial in Brain Metastases

    Purpose:

    Primary Outcome Measures :
    1. Objective response rate in the brain [ Time Frame: Up to 5 years ]
      Assessed per Response Assessment in Neuro-Oncology (RANO) criteria for brain metastases. The response rate is defined as the number of patients who have achieved complete response (CR) or partial response (PR) per RANO for brain metastases criteria during treatment with CDK, PI3K, or NTRK/ROS inhibitors divided by total number of evaluable patients. The response rate and associated exact confidence interval will be estimated within each cohort defined by the targeted agent and histology.


    Secondary Outcome Measures :
    1. Systemic response for extracranial disease [ Time Frame: Up to 5 years ]
      Assessed with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Will be estimated using the systemic response rate (SRR) - where SRR is defined as the number of evaluable patients achieving a response (PR or CR per RECIST 1.1) during treatment with study therapy divided by the total number of evaluable patients. Point estimates will be generated for systemic response rates within each cohort with corresponding 95% binomial confidence intervals.

    2. Clinical benefit rate for central nervous system (CNS) [ Time Frame: Up to 5 years ]
      Evaluated by Response Assessment in Neuro-Oncology (RANO) criteria. Will be estimated as the number of evaluable patients achieving stable disease (SD), partial response (PR), or complete response (CR) as their best objective response during treatment with protocol therapy divided by the total number of evaluable patients. Point estimates will be generated for clinical benefit rates within each cohort with corresponding 95% binomial confidence intervals.

    3. Clinical benefit rate for extracranial disease [ Time Frame: Up to 5 years ]
      Assessed by Response Evaluation Criteria in Solid Tumors (RECIST). Will be estimated as the number of evaluable patients achieving stable disease (SD), partial response (PR), or complete response (CR) as their best objective response (per RECIST for extracranial disease) during treatment with protocol therapy divided by the total number of evaluable patients. Point estimates will be generated for clinical benefit rates within each cohort with corresponding 95% binomial confidence intervals.

    4. Duration of response for brain metastases [ Time Frame: From the time measurement criteria are met for CR or PR for brain metastases until the first date that progressive CNS disease or death is documented, assessed up to 5 years ]
      Duration of response for brain metastases is defined for all evaluable patients who have achieved a confirmed response as the time from the date at which the patient's objective status for brain metastases is first noted to be a CR or PR (per Response Assessment in Neuro-Oncology [RANO] for brain metastases) to the date of the earliest progressive CNS disease is documented or death. The median and 95% confidence intervals will be estimated using the Kaplan-Meier estimator. No formal comparison will be made among the cohorts.

    5. Duration of response for extracranial disease [ Time Frame: From the time measurement criteria are met for CR or PR for extracranial disease until the first date that progressive disease for extracranial disease or death is documented, assessed up to 5 years ]
      Duration of response for extracranial disease is defined for all evaluable patients who have achieved a confirmed response as the time from the date at which the patient's objective status for extranial disease is first noted to be a CR or PR (per RECIST1.1) to the date of the earliest progression (PD) for extracranial disease is documented or death. The median and 95% confidence intervals will be estimated using the Kaplan-Meier estimator. No formal comparison will be made among the cohorts.

    6. Progression-free survival (PFS) - intracranial [ Time Frame: From first day of study treatment to the earliest date documentation of intracranial disease progression or death from any cause, assessed up to 5 years ]
      Intracranial PFS is defined as the time from the first day of study treatment to the earliest date of intracranial disease progression (per RANO for brain metastases) or death from any cause, whichever comes first. The median and 95% confidence intervals will be estimated using the Kaplan-Meier estimator. No formal comparison will be made among the cohorts.

    7. Progression-free survival (PFS) - extracranial [ Time Frame: From the first day of study treatment to the earliest date of documentation of extracranial disease progression or death from any cause, assessed up to 5 years ]
      Extracranial PFS is defined as the time from the first day of study treatment to the earliest date of extracranial disease progression (per RECIST1.1) or death from any cause, whichever comes first. The median and 95% confidence intervals will be estimated using the Kaplan-Meier estimator. No formal comparison will be made among the cohorts.

    8. Site of first progression [ Time Frame: Up to 24 months ]
      The site of first progression will be estimated descriptively within each cohort within 12 and 24 months after starting protocol treatment. The first progression is defined as the first documented central nervous system (CNS) progression per Response Assessment in Neuro-Oncology (RANO) or extracranial progression per Response Evaluation Criteria in Solid Tumors (RECIST), whichever occurs first. The percentage of extracranial progression at first progression within 12 and 24 months after starting protocol treatment will be estimated as number of patients who experience the first progression which is extracranial progression divided by number of patients who are still at risk up to 12 and 24 months, respectively.

    9. Overall survival [ Time Frame: From the first day of study treatment to death due to any cause, assessed up to 5 years ]
      Overall survival is defined as the time from the first day of study treatment to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. No formal comparison will be made among the cohorts.

    10. Incidence of adverse events [ Time Frame: Up to 5 years ]
      Assessed per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, toxicity is defined as adverse events that are classified as possibly, probably, or definitely related to study treatment. Toxicities will be evaluated via the ordinal CTCAE standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by patient and treatment cohort will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of the analysis. No formal comparison will be made among the cohorts.

    TRIAL NUMBER: N0577

    Title: N0577 (CODEL): Phase III Intergroup Study of Radiotherapy with Concomitant and Adjuvant Temozolomide versus Radiotherapy with Adjuvant PCV Chemotherapy in Patients with 1p/19q Co-deleted Anaplastic Glioma or Low Grade Glioma

    Purpose: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving radiation with concomitant and adjuvant temozolomide versus radiation with adjuvant PCV is more effective in treating anaplastic glioma or low grade glioma.

    TRIAL NUMBER: WF-1801

    Title: A Single Arm, Pilot Study of Ramipril for Preventing Radiation-Induced Cognitive Decline in Glioblastoma (GBM) Patients Receiving Brain Radiotherapy

    Purpose: This study is to determine if an oral drug called Ramipril can lower the chance of memory loss in patients with glioblastoma getting chemoradiation. Patients will take Ramipril during chemoradiation and continue until 4 months post-treatment. Memory loss will be assessed using several neurocognitive tests throughout the duration of the study.

    TRIAL NUMBER: EA1151

    Title: Digital Tomosynthesis Mammography and Digital Mammography in Screening Patients for Breast Cancer

    Purpose: This randomized phase III trial studies digital tomosynthesis mammography and digital mammography in screening patients for breast cancer. Screening for breast cancer with tomosynthesis mammography may be superior to digital mammography for breast cancer screening and may help reduce the need for additional imaging or treatment.

    TRIAL NUMBER: EA1181

    Title: CompassHER2-pCR: PREOPERATIVE THP AND POSTOPERATIVE HP IN PATIENTS WHO ACHIEVE A PATHOLOGIC COMPLETE RESPONSE PART 1 COMPONENT OF: THE CompassHER2 TRIALS (COMPREHENSIVE USE OF PATHOLOGIC RESPONSE ASSESSMENT TO OPTIMIZE THERAPY IN HER2-POSITIVE BREAST CANCER)

    Purpose:

    Primary Outcome Measures :
    1. Recurrence-free survival (RFS) [ Time Frame: Up to 3 years after end of treatment ]
      Events include recurrence of ipsilateral invasive breast tumor, recurrence of locoregional invasive breast tumor, and distant recurrence. Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and estrogen receptor (ER) status. Greenwood method will be used to estimate the 95% confidence interval for 3-year rate.


    Secondary Outcome Measures :
    1. Invasive disease-free survival (IDFS) [ Time Frame: Up to 3 years after the end of treatment ]
      Events include recurrence of ipsilateral invasive breast tumor, recurrence of locoregional invasive breast tumor, distant recurrence, contralateral invasive breast cancer, and second primary non-breast invasive cancer (other than squamous or basal cell skin cancer). Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

    2. Distant disease-free survival (DDFS) [ Time Frame: Up to 3 years after the end of treatment ]
      Events include distant recurrence and second primary non-breast invasive cancer (other than squamous or basal cell skin cancer). Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

    3. Distant relapse-free survival (DRFS) [ Time Frame: U to 3 years after the end of treatment ]
      Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

    4. Recurrence-free interval (RFI) [ Time Frame: Up to 3 years after the end of treatment ]
      Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

    5. Overall survival (OS) [ Time Frame: From date of surgery until the date of death from any cause, assessed up to 3 years after the end of treatment ]
      Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

    6. Event-free survival (EFS) [ Time Frame: Up to 3 years after the end of treatment ]
      Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

    7. Incidence of adverse events (AEs) [ Time Frame: Up to 1 week after cycle 4 (all patients) and/or up to cycle 13 post-surgery (Arm A only) (each cycle is 21 days) ]
      Will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. All treatment-emergent and baseline adverse events and hematological/biochemical toxicities based on laboratory measurements, as well as drug related AEs, will be summarized by NCI CTCAE v5.0 worst grade. The incidence of deaths and treatment-emergent serious adverse events (defined as number of patients experiencing the AE divided by all treated patients) will be summarized using binominal proportions and binomial exact 95% confidence intervals. The incidence of adverse events leading to discontinuation of protocol therapy will be summarized and listed as well.

    TRIAL NUMBER: NRG-BR003

    Title: A Randomized Phase III Trial of Adjuvant Therapy Comparing Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel With or Without Carboplatin for Node-Positive or High-Risk Node-Negative Triple-Negative Invasive Breast Cancer

    Purpose: This randomized phase III trial studies how well doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel with or without carboplatin work in treating patients with triple-negative breast cancer. Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether doxorubicin hydrochloride and cyclophosphamide is more effective when followed by paclitaxel alone or paclitaxel and carboplatin in treating triple-negative breast cancer.

    TRIAL NUMBER: NRG-BR004

    Title: A Randomized, Double-Blind, Phase III Trial of Paclitaxel/Trastuzumab/Pertuzumab With Atezolizumab or Placebo in First-Line HER2-Positive Metastatic Breast Cancer

    Purpose: his randomized phase III trial studies how well paclitaxel, trastuzumab, and pertuzumab with or without atezolizumab works in treating patients with breast cancer that has spread to other parts of the body. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as trastuzumab, pertuzumab, and atezolizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving paclitaxel, trastuzumab, and pertuzumab with or without atezolizumab may kill more tumor cells.

    TRIAL NUMBER: S1418

    Title: A Randomized, Phase III Trial to Evaluate the Efficacy and Safety of MK-3475 (Pembrolizumab) as Adjuvant Therapy for Triple Receptor-Negative Breast Cancer With ? 1 cm Residual Invasive Cancer or Positive Lymph Nodes (ypN+) After Neoadjuvant Chemotherapy

    Purpose: This randomized phase III trial studies how well pembrolizumab works in treating triple-negative breast cancer. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

    TRIAL NUMBER: S1703

    Title: S1703; Randomized Non-Inferiority Trial Comparing Overall Survival of Patients Monitored with Serum Tumor Marker Directed Disease Monitoring (STMDDM) versus Usual Care in Patients with Metastatic Hormone Receptor Positive Breast Cancer

    Purpose: To assess whether patients with HER-2 negative, hormone receptor positive, metastatic breast cancer who are monitored with serum tumor marker directed disease monitoring (STMDDM) have non-inferior overall survival compared to patients monitored with usual care.

    TRIAL NUMBER: S1706

    Title: A PHASE II RANDOMIZED TRIAL OF OLAPARIB (NSC-747856) ADMINISTERED CONCURRENTLY WITH RADIOTHERAPY VERSUS RADIOTHERAPY ALONE FOR INFLAMMATORY BREAST CANCER

    Purpose: Primary Outcome Measures : Invasive Disease-Free Survival (IDFS) [ Time Frame: Up to 8 years ] Time from date of registration to date of first invasive recurrence (local, regional or distant), second invasive primary cancer (breast or not), or death due to any cause. Patients last known to be alive who have not experienced recurrence or second primary cancer are censored at their last contact date. Analysis will be on an intent-to-treat basis and will estimate the survival endpoints using the product-limit method of Kaplan and Meier and will compare the time-to-event distributions using log-rank test statistics. Hazard ratios will be calculated from Cox regression analyses. Effect modification by the stratification variables will be tested as interactions with treatment and separate hazard ratios with 95% confidence intervals by major subgroups will be displayed in a forest plot to examine for consistency of the treatment effect over these subgroups. Secondary Outcome Measures : Locoregional Recurrence-Free Interval (Local Disease-Free Interval (LDFI)) [ Time Frame: Up to 8 years ] Time from date of registration to date of invasive local or regional recurrence. Patients last known to be alive without recurrence are censored at their last contact date. Patients with distant recurrence, second primary cancer or death are censored at the time of that event. A competing risk framework will be conducted separating out the event types of locoregional recurrence from distant recurrence and death. Hazard ratios will be calculated from Cox regression analyses. Effect modification by the stratification variables will be tested as interactions with treatment and separate hazard ratios with 95% confidence intervals by major subgroups will be displayed in a forest plot to examine for consistency of the treatment effect over these subgroups. Distant Relapse-Free Survival (Distant Recurrence-Free Survival) [ Time Frame: Up to 8 years ] Time from date of registration to date of invasive distant disease recurrence, second invasive primary cancer (breast or not) or death due to any cause. Patients last known to be alive who have not experienced disease recurrence, or second primary cancer are censored at their last contact date. Overall Survival [ Time Frame: Up to 8 years ] Time from date of registration to date of death due to any cause. Patients last known to be alive are censored at their last contact date.

    TRIAL NUMBER: URCC 16070

    Title: Netupitant/Palonosetron Hydrochloride and Dexamethasone With or Without Prochlorperazine or Olanzapine in Improving Chemotherapy-Induced Nausea and Vomiting in Patients With Breast Cancer

    Purpose: This randomized phase III trial studies how well netupitant/palonosetron hydrochloride and dexamethasone with prochlorperazine or olanzapine work compared to netupitant/palonosetron hydrochloride and dexamethasone in improving chemotherapy-induced nausea and vomiting in patients with breast cancer. Antiemetic drugs, such as prochlorperazine and olanzapine, may help lessen nausea and vomiting in patients with breast cancer treated with chemotherapy.

    TRIAL NUMBER: WF 97116

    Title: Phase 3 Randomized Placebo Controlled Clinical Trial of Donepezil - WF 97116

    Purpose: This study is to compare the safety and effects of donepezil (Aricept) or if it decreases memory loss after receiving chemotherapy for breast cancer.

    TRIAL NUMBER: DCP-001

    Title: DCP-001, Use of a Clinical Trial Screening Tool to Address Cancer Health Disparities in the NCI Community Oncology Research Program (NCORP)

    Purpose: The protocol is not a scientific study; rather, a method to implement the screening tool and allow the collection and analyses of expanded data with informed consent. Investigators also enroll patients into NCI-treatment trials. The tool, based on a screening log successfully used within the NCI Community Cancer Centers Program (NCCCP), has been streamlined and integrated into the sites’ workflow by using OPEN. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. Also missing from the existing data is the context of care, within the communities themselves where most cancer and at risk of cancer patients receive care which is the focus of NCORP. The profile of patients accrued to NCI-sponsored clinical trials lacks both racial/ethnic and socioeconomic diversity. Accrued patients tend to be insured, highly educated and of higher socioeconomic means. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. NCORP's clinical trials portfolio includes cancer control, prevention, screening, symptom science, and cancer care delivery research.

    TRIAL NUMBER: DCP-002

    Title: DCP-002 Early Onset Malignancies Initiative (EOMI): Molecular profiling of Breast, Prostate, Colorectal, Liver, Kidney, and Multiple Myeloma among Racially and Ethnically Diverse Populations

    Purpose: The primary objective of the EOMI (Early Onset Malignancy Initiative) is to acquire tissue and blood, and other biospecimens for research purposes from tests performed for clinical care or for research indications on other research protocols to accelerate our understanding of the molecular basis of early onset cancers occurring in racial and/or ethnic minority populations through the application of genome analysis technologies, including large-scale genome sequencing and clinical data analysis.

    TRIAL NUMBER: EA2165

    Title: Nivolumab After Combined Modality Therapy in Treating Patients With High Risk Stage II-IIIB Anal Cancer

    Purpose: This randomized phase II clinical trial studies how well nivolumab after combined modality therapy works in treating patients with high risk stage II-IIIB anal cancer. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

    TRIAL NUMBER: S1823

    Title: A PROSPECTIVE OBSERVATIONAL COHORT STUDY TO ASSESS miRNA 371 FOR OUTCOME PREDICTION IN PATIENTS WITH NEWLY DIAGNOSED GERM CELL TUMORS

    Purpose:

    Primary Outcome Measures :
    1. Relapse rate of active germ cell malignancy for those undergoing active surveillance of clinical stage I (CSI)/stage IIA germ cell malignancy [ Time Frame: Up to 3 years ]
    2. Positive predictive value [ Time Frame: Up to 3 years ]

    Biospecimen Retention:   Samples With DNA
    Blood

    TRIAL NUMBER: A031702

    Title: Phase II Study of Cabozantinib in Combination with Nivolumab and Ipilimumab in Rare Genitourinary Tumors

    Purpose: Primary Outcome Measures :
    Objective response rate (ORR) [ Time Frame: Up to 5 years ] An objective response is defined as a confirmed complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. Will be estimated by the number of confirmed objective responses divided by the total number of evaluable patients. Confidence intervals for the true ORR will be calculated.

    Secondary Outcome Measures :
    Duration of response [ Time Frame: From time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years ] Defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented.
    Progression-free survival (PFS) [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 5 years ] The median its 95% confidence interval will be determined and will be summarized using the Kaplan-Meier estimator.
    Overall survival [ Time Frame: Up to 5 years ] The median its 95% confidence interval will be determined and will be summarized using the Kaplan-Meier estimator.
    Clinical benefit rate (CBR) [ Time Frame: Up to 5 years ] A confirmed clinical benefit is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart or a confirmed stable disease at two consecutive tumor assessments at least 3 months apart. The CBR will be estimated by the number of patients with confirmed clinical benefit divided by the total number of evaluable patients. Confidence intervals for the true CBR will be calculated using exact binomial confidence intervals.
    Incidence of adverse events (AE) [ Time Frame: Up to 5 years ] Will be assessed using Common Terminology Criteria for Adverse Events version 5.0. The maximum of a particular AE will be determined for each patient. Tables will summarize the number and relative frequency of patients observing an AE as well as the number and relative frequency of patients experiencing any AE of grade 3 or greater.

    Other Outcome Measures:
    Effects of treatment in patients with bone-only disease [ Time Frame: Up to 5 years ] The bone-only tumor patients will be evaluated in an exploratory fashion (if no RECIST measurements are available). A maximum of 15 patients with bone-only disease will be enrolled and evaluated using PFS for a descriptive analysis of the effect of treatment.

    TRIAL NUMBER: NRG GU005

    Title: Phase III IGRT and SBRT Vs IGRT and Hypofractionated IMRT for Localized Intermediate Risk Prostate Cancer

    Purpose: 1. OBJECTIVES 1.1 Primary Objectives ? To determine whether SBRT can be shown to be superior to hypofractionated IMRT in terms of GU and GI toxicity by having fewer patients that experience a minimal important decline (MID) in urinary irritation/obstructive and bowel HRQOL as measured by EPIC-26 at 24 months post completion of therapy. ? To determine if SBRT (5 fractions of 7.25 Gy) is superior to hypofractionated IMRT (28 fractions of 2.5 Gy) as measured by Disease Free Survival (DFS) 1.2 Secondary Objectives ? Secondary ObjectivesTo determine whether SBRT can be shown to be superior to hypofractionated IMRT at 12 and 24 months post completion of therapy in terms of HRQOL by having fewer patients that experience a minimal important decline (MID) bowel (12 months only) sexual, hormonal, urinary irritation/obstructive (12 months only) and in urinary incontinence HRQOL as measured by EPIC-26 ? To determine if SBRT (5 fractions of 7.25 Gy) is superior to hypofractionated IMRT (28 fractions of 2.5 Gy) as measured by biochemical failure, overall survival, local failure, prostate cancer specific survival, and distant metastases ? To determine the correspondence between the diagnostic MRI and biopsy 1.3 Exploratory Objectives ? To determine whether a potentially more expensive therapy, SBRT, would be cost-effective than standard hypofractionated IMRT as measured by the EQ-5D-5L ? To explore the relationship between PIRADSv2 grade with biochemical failure ? Collect specimens for future translational research analyses

    TRIAL NUMBER: WF-1802

    Title: Influence of Primary Treatment for Prostate Cancer on Work Experience (PCW)

    Purpose: The objective of this study is to examine how adenocarcinoma of the prostate treatment differentially affects African American men's ability to work and to describe and compare changes in work ability (as measured through self-reported global work ability item) reported by African American and white adenocarcinoma of the prostate survivors before treatment and 6 months after treatment completion.

    TRIAL NUMBER: ChemoID

    Title: STANDARD CHEMOTHERAPY VERSUS CANCER STEM CELL ASSAY DIRECTED CHEMOTHERAPY IN RECURRENT PLATINUM RESISTANT OVARIAN CANCER

    Purpose:

    Primary Outcome Measures :
    1. Objective response rate [ Time Frame: 24 months ]
      Objective response rate (ORR) as measured by RECIST version 1.1 criteria in recurrent EOC patients who have had ChemoID-guided treatment versus physician choice control treatment (chemotherapy chosen by the physician from the provided list).


    Secondary Outcome Measures :
    1. Progression Free Survival (PFS) [ Time Frame: 24 months ]
      Progression free survival (PFS) in patients with recurrent epithelial ovarian cancer (EOC) who receive standard of care treatment (chemotherapy chosen by the physician from the provided list) versus ChemoID drug response assay-directed chemotherapy.

    2. Duration of Response [ Time Frame: 24 months ]
      Duration of Response (DOR) in patients with recurrent epithelial ovarian cancer (EOC) who receive standard of care treatment (chemotherapy chosen by the physician from the provided list) versus ChemoID drug response assay-directed chemotherapy.

    3. CA125 levels [ Time Frame: 24 months ]
      Levels of CA125 in patients with recurrent epithelial ovarian cancer (EOC) who receive standard of care treatment (chemotherapy chosen by the physician from the provided list) versus ChemoID drug response assay-directed chemotherapy.

    4. Health-Related Quality of Life (HRQOL) [ Time Frame: 24 months ]
      Health-Related Quality of Life (HRQOL) measured to ChemoID-guided treatment selection vs. standard chemotherapy chosen by the physician using self-reported and validated questionnaires, addressing physical, psychological, emotional, and social issues.

    TRIAL NUMBER: GOG 0263

    Title: RANDOMIZED PHASE III CLINICAL TRIAL OF ADJUVANT RADIATION VERSUS CHEMORADIATION IN INTERMEDIATE RISK, STAGE I/IIA CERVICAL CANCER TREATED WITH INITIAL RADICAL HYSTERECTOMY AND PELVIC LYMPHADENECTOMY

    Purpose: PRIMARY OBJECTIVES:
    I. To determine if post-operative adjuvant chemoradiotherapy (CRT) can significantly improve recurrence-free survival (RFS) when compared to radiation therapy (RT) alone in patients with intermediate- risk factors stage I- IIA cervical cancer after treatment with radical hysterectomy.
    SECONDARY OBJECTIVES:
    I. To compare the overall survival (OS) of patients treated with these regimens.
    II. To assess differences in incidence and severity of regimen-attributed adverse events in these patients.
    III. To provide assessment of patient risk vs benefit (positive study only). IV. To determine whether post-operative adjuvant CRT improves the health- related quality-of-life compared to RT alone.
    V. To compare toxicity profiles with particular focus on treatment-related genitourinary, gastrointestinal, neurological, pain, and sexual adverse events in these patients.
    TERTIARY OBJECTIVES:
    I. To bank archival tumor tissue for research studies, including studies that evaluate the association between biomarkers, RFS, OS, and clinical-surgical- pathologic characteristics in patients treated with these regimens.
    II. To bank DNA from whole blood for research studies, including studies that evaluate associations between single nucleotide polymorphisms (SNPs), and measures of clinical outcome, including RFS, OS, and adverse events in patients treated with these regimens.
    OUTLINE: This is a multicenter study. Patients are stratified according to capillary-lymphovascular space involvement (positive vs negative), stromal invasion (deep vs middle vs superficial), radiotherapy modality (external- beam radiation therapy [EBRT] vs intensity-modulated radiation therapy [IMRT]), and cooperative group (KGOG vs GOG). Patients are randomized to 1 of 2 treatment arms.
    ARM I: Patients undergo pelvic EBRT or IMRT 5 days a week for 5.5 weeks.
    ARM II: Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in arm I. Treatment with cisplatin repeats every 7 days for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
    Patients complete questionnaires on smoking history, Functional Assessment of Cancer Therapy (FACT-G, Version 4), FACT-Neurotoxicity subscale, and the Brief Pain Inventory (BPI) at baseline and periodically during study.
    Tumor tissue and blood samples may be collected and banked for future biomarker and other analysis.
    After completion of study therapy, patients are followed up every 3 months for 2 years, and then every 6 months for 3 years.

    TRIAL NUMBER: NRG-GY006

    Title: A Randomized Phase II Trial of Radiation Therapy and Cisplatin Alone or in Combination with Intravenous Triapine in Women with Newly Diagnosed Bulky Stage IB2, Stage II, IIIB, or IVA Cancer of the Uterine Cervix or Stage II-IVA Vaginal Cancer

    Purpose: This randomized phase II trial studies radiation therapy and cisplatin with triapine to see how well they work compared to the standard radiation therapy and cisplatin alone in treating patients with newly diagnosed stage IB2, II, or IIIB-IVA cervical cancer or stage II-IVA vaginal cancer. Radiation therapy uses high energy protons to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether radiation therapy and cisplatin are more effective with triapine in treating cervical or vaginal cancer.

    TRIAL NUMBER: NRG-GY019

    Title: A RANDOMIZED PHASE III, TWO-ARM TRIAL OF PACLITAXEL/CARBOPLATIN/MAINTENANCE LETROZOLE VERSUS LETROZOLE MONOTHERAPY IN PATIENTS WITH STAGE II-IV, PRIMARY LOW-GRADE SEROUS CARCINOMA OF THE OVARY OR PERITONEUM

    Purpose:

    Primary Outcome Measures :
    1. Progression-free survival (PFS) [ Time Frame: Time from the randomized treatment assignment to documentation of disease progression (Response Evaluation Criteria in Solid Tumors 1.1) or death from any cause, whichever comes first, assessed up to 8 years ]
      The PFS comparison will be assessed at the second interim and final analyses using a logrank test stratified by country and residual disease status. Estimates for the letrozole/letrozole (L/L) vs paclitaxel/carboplatin/letrozole (CT/L) hazard ratio and its confidence interval will be obtained using a stratified Cox proportional hazards model. Potential confounding factors, including the stratification factors, performance status and self-declared racial designation will be considered in a final exploratory model. A forest plot of treatment hazard ratios with confidence intervals within subgroups will also be reported. PFS will be characterized by treatment group with Kaplan-Meier plots and estimates of the median PFS.


    Secondary Outcome Measures :
    1. Incidence of adverse events (AE) [ Time Frame: Up to 8 years ]
      The nature, frequency and degree of toxicity will be tabulated at the System Organ Class and AE Term levels using Common Terminology Criteria for Adverse Events version 5.0. Each patient will be represented according the maximum grade observed for each term, within randomized treatment assignment. Tabulations will show the number and percentage of patients by maximum grade, within their randomized treatment assignment.

    2. Objective response rate (ORR) [ Time Frame: Up to 8 years ]
      Will be estimated as the binomial proportion of patients with best overall response of complete response (CR) or partial response (PR) among patients with measurable disease after cytoreductive surgery. Response rates and their 95% Wilson-Score confidence intervals will be estimated for each treatment arm, using the randomized treatment assignment. The odds-ratio for ORR in the L/L vs CT/L arms will be estimated from the multivariable logistic regression model adjusted for stratification factors.

    3. Duration of response [ Time Frame: Time from documentation of response under documentation of progression or death, which is observed first, assessed up to 8 years ]
      Will be defined among patients with best overall response of CR or PR. Comparison of response duration between the randomized treatment arms will be supported by Kaplan Meier methods, and the corresponding estimates for median duration and its 95% confidence intervals.

    4. Overall survival (OS) [ Time Frame: Time between randomization and death from any cause, assessed up to 8 years ]
      Differences in OS across the randomized treatment groups will be assessed using Kaplan Meier methods, with median time to death estimates and the corresponding 95% confidence intervals. The L/L vs CT/L hazard ratio will be estimated by a proportional hazards model stratified by the randomization stratification factors.

    5. Adherence to letrozole maintenance therapy [ Time Frame: At cycles 1, 6, and 12 ]
      Will be quantified as the mean rate of adherence (MRA), calculated as the proportion of product not returned divided by the number of days since the previous visit at which study products were dispensed. Currently, the letrozole is delivered in a 2.5 mg pill, and the recommended dose is 2.5 mg per day. This outcome will be computed for each treatment cycle (generally 21 days). The mean MRA will be compared between the randomized treatment groups using linear mixed model methods. The model will be specified with a random patient effect, and fixed effects for randomized treatment indicator, time (cycle number) and the interaction, with an adjustment for the protocol stratification factors. Primary interest is in the difference in mean (MRA) at cycles 1, 6 and 12 between the treatment group. The results will be reported as the estimated mean (MRA) and 95% confidence intervals for each treatment/time combination. Treatment differences within stratification factors may also be considered.

    TRIAL NUMBER: RTOG-0724

    Title: PHASE III RANDOMIZED STUDY OF CONCURRENT CHEMOTHERAPY AND PELVIC RADIATION THERAPY WITH OR WITHOUT ADJUVANT CHEMOTHERAPY IN HIGH-RISK PATIENTS WITH EARLY-STAGE CERVICAL CARCINOMA FOLLOWING RADICAL HYSTERECTOMY

    Purpose: OBJECTIVES:
    Primary ?To determine if administering adjuvant systemic chemotherapy after chemoradiotherapy will improve disease-free survival compared to chemoradiotherapy alone in patients with high-risk early-stage cervical carcinoma found to have positive nodes and/or positive parametria after radical hysterectomy.
    Secondary ?To evaluate adverse events. ?To evaluate overall survival. ?To evaluate quality of life. ?To evaluate chemotherapy-induced neuropathy. ?To perform a post-hoc dose-volume evaluation between patients treated with standard radiotherapy and patients treated with intensity-modulated radiotherapy (IMRT) with respect to toxicity and local control. ?To collect fixed tissue samples to identify tumor molecular signatures that may be associated with patient outcomes, such as adverse events, disease-free survival, and overall survival. ?To collect blood samples to identify secreted factors from serum and plasma that may be associated with adverse events or outcome and to identify single nucleotide polymorphisms (SNPs) in genes from buffy coat that may be associated with a genetic predisposition to tumor formation itself or a response to cytotoxic therapy.
    OUTLINE: This is a multicenter study. Patients are stratified according to planned use of brachytherapy (no vs. yes), radiotherapy modality - [standard external beam radiotherapy (EBRT) vs. intensity-modulated radiotherapy (IMRT)], and radiotherapy dose (45 Gy vs. 50.4 Gy). Patients are randomized to 1 of 2 treatment arms. ?Arm I: Patients undergo standard EBRT or IMRT to the pelvis once daily 5 days a week for 5-6 weeks. Patients also receive concurrent cisplatin IV over 1 hour once weekly for 6 weeks.
    NOTE: Some patients may also undergo brachytherapy beginning within 7 days after completion of radiotherapy. ?Arm II: Patients receive chemoradiotherapy as in arm I. Beginning 4-6 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
    Quality of life is assessed by the Functional Assessment of Cancer Therapy - Gynecologic Oncology Group (FACT-GOG/NTX4), FACT-Cx, and FACIT-D questionnaires at baseline; at the completion of chemoradiotherapy; and then at 6, 12, and 24 months after completion of chemoradiotherapy.
    Blood and tissue samples may be collected for gene expression analysis by immuno-histochemistry (IHC) and for biomarker and polymorphism studies.
    After completion of study treatment, patients are followed up very 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

    TRIAL NUMBER: EA3132

    Title: EA3132:Phase II Randomized Trial of Radiotherapy with or Without Cisplatin for Surgically Resected Squamous Cell Carcinoma of the Head and Neck (SCCHN) with TP53 Sequencing

    Purpose: This phase II trial studies how well radiation therapy with or without cisplatin works in treating patients with stage III-IVA squamous cell carcinoma of the head and neck who have undergone surgery. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known if radiation therapy is more effective with or without cisplatin in treating patients with squamous cell carcinoma of the head and neck.

    TRIAL NUMBER: NRG-HN004

    Title: Randomized Phase II/III Trial of Radiotherapy with Concurrent MEDI4736 (Durvalumab) vs. Radiotherapy with Concurrent Cetuximab in Patients with Stage III-IVB Head and Neck Cancer with a Contraindication to Cisplatin

    Purpose: PRIMARY OBJECTIVES:
    I. To determine whether radiotherapy (RT) with concurrent and adjuvant anti-PD-L1 therapy (durvalumab) is feasible in patients with locoregionally advanced head and neck cancer (HNC) who have a contraindication to cisplatin. (Lead-in) II. To test the hypothesis that concurrent RT and anti-PD-L1 therapy improves progression free survival (PFS) compared to standard therapy (RT with concurrent cetuximab) in patients with locoregionally advanced HNC who have a contraindication to cisplatin. (Phase II) III. To test the hypothesis that concurrent RT and anti-PD-L1 therapy improves overall survival compared to standard therapy (RT with concurrent cetuximab) in patients with locoregionally advanced HNC who have a contraindication to cisplatin. (Phase III)
    SECONDARY OBJECTIVES:
    I. To compare toxicity between patients treated with RT + anti-PD-L1 therapy versus RT/cetuximab.
    II. To test the effect of anti-PD-L1 therapy in the subpopulation of patients with tumors that overexpress PD-L1.
    III. To compare overall survival, response (at 4-month fludeoxyglucose F-18 [FDG]-positron emission tomography [PET]-computed tomography [CT]), locoregional failure, distant metastasis, and competing mortality in the two arms by known risk factors, including p16 status and omega score.
    IV. To test the hypothesis that durvalumab therapy arm will improved 1 year quality of life (QOL) compared to the cetuximab arm using European Organization for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-core [C]30 version 3.0) / Head-and-Neck module (EORTC QLQ/H&N35) and other quality of life (QOL) tools.
    TERTIARY OBJECTIVES:
    I. To test the hypothesis that radiation combined with durvalumab enhances the adaptive immune response using three types of immunophenotyping compared to radiation combined with cetuximab.
    OUTLINE: Patients are randomized to 1 of 2 arms.
    ARM I: Patients receive cetuximab intravenously (IV) over 120 minutes weekly. Treatment repeats every week for up to 8 courses in the absence of disease progression or unacceptable toxicity. Beginning 5-7 days after first cetuximab dose, patients undergo intensity modulated radiation therapy (IMRT) 5 fractions per week for up to 7 weeks.
    ARM II: Patients receive durvalumab IV over 60 minutes every 4 weeks. Treatment repeats every 4 weeks for up to 7 courses in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients undergo IMRT 5 fractions per week for up to 7 weeks.
    After completion of study treatment, patients are followed up at 1 month, every 4 months for 1 year, every 6 months for 2 years, then annually thereafter.

    TRIAL NUMBER: A031704

    Title: PD-Inhibitor (Nivolumab) and Ipilimumab Followed by Nivolumab Vs. VEGF TKI Cabozantinib with Nivolumab: A Phase III Trial in Metastatic Untreated REnal Cell CancEr [PDIGREE]

    Purpose: This phase III trial studies how well nivolumab and ipilimumab, followed by nivolumab versus cabozantinib and nivolumab, work in treating patients with renal cell cancer that is untreated and has spread to other parts of the body. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cabozantinib, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known how well cabozantinib and nivolumab work in treating patients with untreated renal cell cancer that has spread to other parts of the body.

    TRIAL NUMBER: EA8143

    Title: EA8143:A Phase 3 RandOmized Study Comparing PERioperative Nivolumab vs. Observation in Patients with Localized Renal Cell Carcinoma Undergoing Nephrectomy (PROSPER RCC)

    Purpose: The purpose of this study is to compare any good and bad effects of using nivolumab (also known as OPDIVO®), before and after the kidney cancer surgery to using the usual approach of surgically removing the kidney cancer followed by standard post-operative follow-up and monitoring. Nivolumab is a drug that may help stimulate your immune system to attack any cancer cells that may remain after surgery. The addition of nivolumab to the usual surgery could prevent your cancer from returning but it could also cause side effects. This research study will allow researchers to find out whether this different treatment is better, the same, or worse than the usual treatment for kidney cancer that has been removed but is at risk for coming back The study drug, nivolumab, is already FDA-approved for patients who have kidney cancer that has spread outside of the kidney to other organs or lymph nodes. The use of nivolumab in this study is investigational (not approved by the FDA) for your early stage of cancer where we do not know for sure if the disease has spread outside of the kidney. This research study will allow the researchers to know whether this different approach is better, the same, or worse than the usual approach. To be better, the study drug should improve how long you are able to live without any signs or symptoms of your cancer compared to the usual approach

    TRIAL NUMBER: A151216

    Title: Genetic Testing For Patients with Resectable or Resected Lung Cancer: Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST)

    Purpose: PRIMARY OBJECTIVES:
    I. To centrally genotype resected lung adenocarcinomas for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements to facilitate accrual to randomized adjuvant studies.
    II. To obtain clinically annotated tumor tissue and patient-matched non-malignant deoxyribonucleic acid (DNA) from peripheral blood, as well as detailed epidemiologic and clinical follow-up data, to allow clinically annotated advanced genomic analyses in concert with the National Cancer Institute (NCI) Center for Cancer Genomics (CCG).
    SECONDARY OBJECTIVES:
    I. To characterize the natural history of EGFR and ALK wild-type lung cancers to allow subsequent development of targeted therapies against genotype-defined sub-populations in the adjuvant and recurrent settings.
    II. To cross-validate local genotyping assays for EGFR and ALK with a central reference standard.
    TERTIARY OBJECTIVES:
    I. To study the genomic evolution of lung cancers by comparing genomic characteristics at resection and at recurrence.
    OUTLINE:
    Patients undergo collection of blood and tissue samples for EGFR and ALK testing via direct sequencing and fluorescence in situ hybridization (FISH). Patients that have had surgery prior to pre-registration will submit samples from the previous surgery for testing.
    After completion of study, patients that are not enrolled on either A081105 or E4512 are followed up every 6 months for 5 years.

    TRIAL NUMBER: A171901

    Title: Older Non-Small Cell Lung Cancer Patients (>/= 70 Years of Age) Treated With First-Line MK-3475 (Pembrolizumab)+/- Chemotherapy (Oncologist's/Patient's Choice)

    Purpose: This trial studies the side effects of pembrolizumab with or without chemotherapy in treating patients with stage IV non-small cell lung cancer that has come back (recurrent) and has spread to other places in the body (advanced). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as pemetrexed and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab with or without chemotherapy may shrink the tumor in older patients with non-small cell lung cancer.

    TRIAL NUMBER: EA5163

    Title: EA5163/S1709 INSIGNA : A Randomized, Phase III Study of Firstline Immunotherapy Alone or in Combination with Chemotherapy in Induction/Maintenance or Postprogression in Advanced Nonsquamous Non-Small Cell Lung Cancer (NSCLC) with Immunobiomarker SIGNature-Driven Analysis

    Purpose: Primary Outcome Measures : Overall survival (OS) [ Time Frame: From randomization to death from any cause, assessed up to 5 years post treatment ] OS distributions will be estimated using the Kaplan-Meier method.

    Secondary Outcome Measures : Progression-free survival (PFS) [ Time Frame: From randomization to documented disease progression or death from any cause, assessed up to 5 years post treatment ] PFS distributions will be estimated using the Kaplan-Meier method.
    Best objective response [ Time Frame: Up to 5 years post treatment ] Best objective response will be evaluated via Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
    Incidence of adverse events [ Time Frame: Up to 30 days post treatment ] Toxicities will be reported via the Common Terminology Criteria for Adverse Events (CTCAE) criteria version 5.0. Toxicity rates between arms in the overall population will be compared using Fisher's exact tests with a one-sided type I error rate of 1.25%; multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes.
    PD-L1 positivity [ Time Frame: At baseline ] PD-L1 positivity will be defined as >= 1% Tumor Proportion Score (TPS) for the purpose of enrollment onto the trial. Strongly PD-L1 positive is defined as >= 50% TPS; weakly positive is defined as 1% - 49% TPS.

    TRIAL NUMBER: LungMAP

    Title: LungMAP: A MASTER PROTOCOL TO EVALUATE BIOMARKER-DRIVEN THERAPIES AND IMMUNOTHERAPIES IN PREVIOUSLY-TREATED NON-SMALL CELL LUNG CANCER (Lung-MAP Screening Study)

    Purpose: 1.1 Primary Objective of the Master Protocol (LungMAP) The primary objective of this screening study is to test patient specimens to determine eligibility for participation in the biomarker-driven and non-matched sub-studies included within the Lung-MAP umbrella protocol. 1.2 Secondary Objectives a. Screening Success Rate Objective To evaluate the screen success rate defined as the percentage of screened patients that register for a therapeutic sub-study. Screen success rates will be evaluated for the total screened population and by the subset of patients screened following progression on previous therapy or pre-screened on current therapy. b. Translational Medicine Objectives 1. To evaluate circulating tumor DNA (ctDNA) and compare to the FMI Foundation tissue molecular profiling results in patients who submit a new biopsy for screening. 2. To establish a tissue/blood repository

    TRIAL NUMBER: NRG-LU005

    Title: Limited Stage Small Cell Lung Cancer (LS-SCLC): A Phase II/III Randomized Study of Chemoradiation Versus Chemoradiation Plus Atezolizumab

    Purpose: Primary Outcome Measures :
    Progression-free survival (PFS) (Phase II) [ Time Frame: Time from randomization to any documented progression or death due to any cause, whichever occurs first, assessed up to 5 years ] Progressive disease (PD) will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will compare the distributions of PFS between treatment arms using a one-sided stratified log-rank test in all randomized eligible patients. The rates at various timepoints (e.g., every 6 months after randomization) and medians of PFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95% confidence interval (CI) will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Results from an unstratified analysis will also be provided.
    Overall survival (OS) (Phase III) [ Time Frame: Time from randomization to the date of death due to any cause, assessed up to 5 years ] The primary hypotheses for the phase II and III portions will be evaluated by comparing arm 1 to arm 2 based on PFS (phase II) and OS (phase III) using a stratified log-rank test. Hazard ratios will be estimated using a stratified Cox regression model. Event rates over time will be estimated within each treatment group using the Kaplan-Meier method.

    Secondary Outcome Measures :
    PFS (phase III) [ Time Frame: Time from randomization to any documented progression or death due to any cause, whichever occurs first, assessed up to 5 years ] The primary hypotheses for the phase II and III portions will be evaluated by comparing arm 1 to arm 2 based on PFS (phase II) and OS (phase III) using a stratified log-rank test. Hazard ratios will be estimated using a stratified Cox regression model. Event rates over time will be estimated within each treatment group using the Kaplan-Meier method.
    Incidence of adverse events [ Time Frame: Up to 5 years ] For each patient, the maximum severity reported for both immune mediated and non-immune mediated adverse events will be used in the summaries. Adverse events will be summarized regardless of relationship to protocol treatment as assessed by the investigator. All adverse events, adverse events leading to withdrawal, interruption or modification of protocol treatment, Grade >= 3 adverse events, and serious adverse events will be summarized. Deaths and cause of death will be summarized. The rate of treatment-related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE, v.5.0) will be reported with the frequency and severity (e.g., type, grade, and attribution) by arm, the analysis will be performed at the time of both phase II and phase III (if applicable) primary endpoint analyses. All adverse events will be classified as either immune or non-immune mediated.
    Objective response rate (ORR) [ Time Frame: Up to 5 years ] Will be defined as the proportion of all randomized subjects whose best overall response (BOR) is either a complete response (CR) or partial response (PR) per RECIST 1.1 criteria. ORR will be compared using a two-sided 5% level Cochran-Mantel Haenszel (CMH) test stratified by the same stratification factors used for randomization. An associated odds ratio and 95% CI will be calculated. The ORR and its corresponding 95% exact CI will also be calculated by Clopper-Pearson for each treatment arm. The difference in ORR between the two treatment arms along with the two-sided 95% CI will be estimated using the following CMH method of weighting, adjusting for the stratification factors.
    Local control [ Time Frame: Up to 5 years ] Will be defined as freedom from local progression, in which a failure is defined as intrathoracic tumor progression by RECIST 1.1 criteria. Local control will be analyzed as competing risks data based on cause-specific hazards approaches, where deaths without local failure will be considered as a competing event and analyzed as "censoring" of local failure. The rates at various timepoints (e.g., every 6 months after randomization) and medians of PFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95% CI will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Results from an unstratified analysis will also be provided.
    Distant metastases-free survival (DMFS) [ Time Frame: Time between the date of randomization and the first date of documented distant metastases or death due to any cause, whichever occurs first, assessed up to 5 years ] Will compare the distributions of DMFS between treatment arms using a one-sided stratified log-rank test in all randomized eligible patients. The rates at various timepoints (e.g., every 6 months after randomization) and medians of DMFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95% CI will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Results from an unstratified analysis will also be provided.
    Quality of life (QoL) [ Time Frame: Up to 15 months after the end of the 4th cycle of chemotherapy ] Will be measured by the Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI). Fisher's exact test will be used to compare the proportions of patients experiencing clinically meaningful deterioration (CMD) between the two arms. FACT-TOI deterioration rates and associated 95% confidence interval will be calculated for each treatment group, based on all randomized subjects. Clopper-Pearson method will be used for calculating 95% CI. The deterioration rates of each arm will also be compared using the CMH test, stratified by histology. FACT-TOI at baseline and at each subsequent assessment, as well as their change from baseline will be summarized using descriptive statistics by treatment group as randomized. The scores at baseline and subsequent time points, as well the changes from baseline at each time point for each treatment group will be compared using the two-sample t-test.
    Quality-adjusted survival [ Time Frame: Up to 2 years ] Assessed using score from the 5-level EuroQol 5-dimensional questionnaire (EQ-5D-5L). Defined as the weighted sum of different time episodes added up to a total quality-adjusted life-year. Subjects' overall health state on a visual analog scale (VAS) at each assessment time point will be summarized using descriptive statistics by treatment group, as randomized. Proportion of subjects reporting problems for the five EQ-5D-5L dimensions at each assessment time point will be summarized by level of problem and by treatment group, as randomized. Percentages will be based on number subjects assessed at assessment time point. Subjects' overall health state on a visual analog scale (EQ-VAS) at each assessment time point will be summarized using descriptive statistics by treatment group, as randomized. Proportion of subjects reporting problems for the five EQ-5D dimensions at each assessment time point will be summarized by level of problem and by treatment group, as randomized.
    Level of fatigue [ Time Frame: Up to 2 years ] Will be measured by the Patient-Reported Outcomes Measurement Information System (PROMIS). Baseline and PROMIS at each subsequent assessment, as well as their change from baseline will be summarized using descriptive statistics by treatment group as randomized. The change from baseline to subsequent timepoints may be compared between treatment arms using a t-test, or Wilcoxon test if the data is non-normal.
    Blood based tumor mutational burden (bTMB) and tissue-based tumor mutational burden (tTMB) [ Time Frame: Up to 5 years ] Correlation with clinical outcomes will be done by summarizing the statistical power to detect interaction effects (ratio of hazard ratios) of 0.33 when the marker positive prevalence is 20%, at 2-sided significance level of 0.05.

    Other Outcome Measures:
    Patient-reported symptomatic toxicities [ Time Frame: Up to 15 months after completion of chemoradiation therapy ] Will be measured by Patient Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE). For each symptom and each domain (i.e., frequency, severity, and interference), counts and frequencies will be summarized for the worst score experienced by the patient by treatment arm.

    TRIAL NUMBER: RTOG-1308

    Title: RTOG-1308:PHASE III RANDOMIZED TRIAL COMPARING OVERALL SURVIVAL AFTER PHOTON VERSUS PROTON CHEMORADIOTHERAPY FOR INOPERABLE STAGE II-IIIB NSCLC

    Purpose: This randomized phase III trial studies proton chemoradiotherapy to see how well it works compared to photon chemoradiotherapy in treating patients with stage II-III non-small cell lung cancer that cannot be removed by surgery. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor, such as photon or proton beam radiation therapy, may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as paclitaxel, carboplatin, etoposide, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether proton chemoradiotherapy is more effective than photon chemoradiotherapy in treating non-small cell lung cancer.

    TRIAL NUMBER: S1827

    Title: A RANDOMIZED PHASE III TRIAL OF MRI SURVEILLANCE WITH OR WITHOUT PROPHYLACTIC CRANIAL IRRADIATION (PCI) IN SMALL-CELL LUNG CANCER

    Purpose:

    Primary Outcome Measures :
    1. Overall survival (OS) [ Time Frame: From the date of registration to date of death due to any cause, assessed up to 2 years after randomization ]
      Will evaluate OS with magnetic resonance imaging (MRI) surveillance alone and MRI surveillance combined with prophylactic cranial irradiation (PCI) for the treatment of small cell lung cancer (SCLC).


    Secondary Outcome Measures :
    1. Cognitive failure-free survival (CFFS) [ Time Frame: Baseline to first neurocognitive failure CF or death due to any cause, assessed up to 12 months after randomization ]
      The comparison of CFFS up to 12 months between the arms will be done using a 1-sided 5% level log-rank test.

    2. CFFS rate [ Time Frame: Baseline to first neurocognitive failure CF or death due to any cause, assessed at 90, 180, 270, 360, 540, and 720 days after randomization ]
      There will be a comparison of the CFFS rates between the arms at each of the assessment times and the cumulative incidence of cognitive failure, evaluating death as a competing risk. The CFFS rates at the landmark times will be estimated using the method of Kaplan-Meier and the difference in rates will be evaluated using a 90% confidence interval using Greenwood?s formula.

    3. Cumulative incidence of cognitive failure [ Time Frame: Neurocognitive function test will be assessed at 90, 180, 270, 360, 540, and 720 days after randomization ]
      The cumulative incidence of cognitive failure in the presence of the competing risk of death will be estimated used the method of Fine and Gray.

    4. OS in an "as-treated" analysis [ Time Frame: From the date of registration to date of death due to any cause, assessed up to 2 years after randomization. Patients will be seen at day 90, 180, 270, 360, 540, and 720 ]
      The comparison of OS in the ?as-treated? analysis will be done as described for the primary analysis, however patients will be categorized per treatment received (patients who do not accept their randomized assignment will be analyzed per treatment received). The number of patients not accepting the randomized assignment will also be summarized.

    5. Brain metastases-free survival (BMFS) [ Time Frame: Up to 2 years after randomization. Patients will have MRI on day 90, 180, 270, 360, 540, and 720 ]
      This will be estimated using the method of Kaplan-Meier and comparisons will be done using a log-rank test at the 1-sided 0.05 level. Hazard ratios and associated confidence intervals will be estimated using a Cox Proportional hazards model. Confidence intervals for medians will be estimated using the method of Brookmeyer-Crowley.

    6. Incidence of adverse events [ Time Frame: Up to 2 years after randomization. Patients will be assessed for adverse event after PCI (for patients on PCI + MRI arm) and at month 3 (all patients) ]
      Binary proportions and associated confidence intervals will be estimated.

    TRIAL NUMBER: A051701

    Title: RANDOMIZED PHASE II/III STUDY OF VENETOCLAX (ABT 199) PLUS HEMOIMMUNOTHERAPY FOR MYC/BCL2 DOUBLE-HIT AND DOUBLE EXPRESSING LYMPHOMAS

    Purpose:

    Primary Outcome Measures :
    1. Progression-free survival (PFS) (phase II) [ Time Frame: From randomization date until the earlier of disease progression, or death from any cause, assessed up to 10 years ]
      Will be compared between the experimental and control arms using a stratified log-rank test. If one of the strata has 0 events or there are numerical issues due to the sparseness of the date within strata, an unstratified log-rank test will be used. The Kaplan-Meier method will be used to estimate PFS distributions. One-year PFS estimates, medians, and corresponding hazard ratios will be provided with 95% confidence intervals for each of the double hit lymphoma (DHL) and double expressing lymphoma (DEL) cohorts.

    2. PFS (phase III) [ Time Frame: At 24 months ]
      Will be compared between the experimental and control arms using a Mantel-Haenszel test without a continuity correction. In the event that there is censoring prior to 24 months, a test based on the complementary log-log transformation of Kaplan-Meier estimates will compare PFS at 24 months between experimental and control arms. Two-year PFS estimates, medians, and corresponding hazard ratios will be provided with 95% confidence intervals overall.


    Secondary Outcome Measures :
    1. Overall survival (OS) (phase III) [ Time Frame: From randomization date until death from any cause, assessed up to 10 years ]
      Using a modified intent-to-treat approach, all eligible patients who are centrally confirmed as having a DHL/DEL subtype will be considered evaluable and included in the analysis of the key secondary endpoint in the arm to which they were randomized and under the centrally designated subtype. OS will be compared between the experimental and control arms using a stratified log-rank test. Two-year OS estimates, medians, and corresponding hazard ratios will be provided with 95% confidence intervals overall.

    2. Event-free survival [ Time Frame: From randomization date until the earlier of non-protocol lymphoma therapy, disease progression, or death from any cause, assessed up to 10 years ]
      Will be compared between the experimental and control arms using a log-rank test. Estimated using Kaplan-Meier method by arm and lymphoma subtype.

    3. Response rate [ Time Frame: Up to 1 week after end of cycle 6 ]

      Response will be evaluated using the Lugano criteria for lymphoma response. Best achieved response rate with the intervention will be determined, defined as the number of patients who attain a complete or partial response using positron emission tomography (PET)/computed tomography (CT) out of the total number of evaluable patients who are randomized.

      Response rates will be compared between arms using a chi-square test once all patients on the study have been evaluated for response. Response rates will be estimated by arm and lymphoma subtype with 95% confidence intervals. Logistic regression will be used in a multivariable analysis to identify baseline variables associated with response.


    4. Inconsistency of local and central results for DEL or DHL status [ Time Frame: Until last patient is registered, up to month 57 ]
      Estimated by the number of patients with a local determination of DHL but not central determination of DHL (i.e., positive for DEL or negative for both DHL and DEL) or local determination of DEL but not central determination of DEL (i.e., positive for DHL or negative for both DHL and DEL) divided by the total number of registered patients with adequate material/tissue for central review.

    TRIAL NUMBER: 10231

    Title: NCORP TISSUE PROCUREMENT PROTOCOL: AN NCI CANCER MOONSHOT(SM) STUDY

    Purpose: Primary Outcome Measures : Obtaining tumor tissue and blood specimens [ Time Frame: Up to 2 years ] Will obtain tumor tissue and blood specimens for biobanking and to store tissues, blood, and nucleic acids for future research, including the study of matched pre and post-treatment tumor biopsies to elucidate mechanisms of resistance. Cases will be grouped according to histology and/or treatment. Secondary Outcome Measures : Tumor tissues storage in the Biopathology Center (BPC) at Nationwide Children?s Hospital (NCH) (Biorepository) [ Time Frame: Up to 2 years ] Genomic analysis [ Time Frame: Up to 2 years ] Will perform genomic studies, including a pan-cancer gene panel, and contribute molecular data to the genomic data commons. Biospecimen Retention: Samples With DNA Blood, tissue

    TRIAL NUMBER: A231601CD

    Title: A231601CD: Improving Surgical Care and Outcomes in Older Cancer Patients Through Implementation of an Efficient Pre-Surgical Toolkit (OPTI-Surg)

    Purpose: This trial studies how well the use of a pre-surgical toolkit (OPTI-Surg) works in improving surgical care and outcomes in older participants with cancer. In many elderly patients, surgery can greatly affect physical condition and the ability to return to pre-surgery levels of physical functioning. Providing pre-surgical recommendations may help improve participants' recovery rate and functioning after surgery.

    TRIAL NUMBER: S1609

    Title: SWOG 1609: DART: Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors Treatment with Ipilimumab and Nivolumab for Rare Cancers

    Purpose: Both Ipilimumab and Nivolumab have already been FDA-approved to treat other cancers. However, Ipilimumab and Nivolumab are investigational and not FDA-approved for use in combination in treating rare cancers or cancers of unknown primary origin.

    TRIAL NUMBER: S1714

    Title: A PROSPECTIVE OBSERVATIONAL COHORT STUDY TO DEVELOP A PREDICTIVE MODEL OF TAXANE-INDUCED PERIPHERAL NEUROPATHY IN CANCER PATIENTS

    Purpose: 1.1 Primary Objective a. To develop and validate a clinical risk prediction model using clinical factors for the development of peripheral neuropathy in patients receiving taxane-based chemotherapy regimens. 1.2 Secondary Objectives a. To examine patient-reported outcomes (PROs) and objective measures of chemotherapy induced peripheral neuropathy (CIPN) to better define the phenotype of peripheral neuropathy in this patient population. b. To assess the incidence of CIPN within one year in this patient population. c. To identify predictors of treatment dose reductions, delays, and discontinuations associated with CIPN symptoms in this patient population. 1.3 Other Objectives a. To collect serum and plasma samples for future testing for biomarker and mechanistic studies of CIPN.

    TRIAL NUMBER: A151804

    Title: Establishment of a National Biorepository to Advance Studies of Immune-Related Adverse Events

    Purpose: This trial collects research data and samples from patients who experience immunotherapy side effects to store for use in future research studies. Studying research data and samples from patients who experience immunotherapy side effects may help researchers better understand how to predict, prevent, and treat these side effects.

    TRIAL NUMBER: S1803

    Title: S1803; Phase III Study of Daratumumab/rHuPH20 (NSC- 810307) + Lenalidomide or Lenalidomide as Post-Autologous Stem Cell Transplant Maintenance Therapy in Patients with Multiple Myeloma (MM) Using Minimal Residual Disease to Direct Therapy Duration (DRAMMATIC Study)

    Purpose: Patients are enrolled to screening (Reg Step 1) prior to or after ASCT but prior to Reg Step 2. Patients are followed until they will begin Maintenance and then registered to Reg Step 2 (first randomization). Patients are randomized between Lenalidomide for 2 years and Lenalidomide + Daratumumab/rHuPH20. After 2 years of Maintenance, MRD is assessed to guide further therapy. MRD-positive patients will continue with the assigned treatment. MRD-negative patients will be further randomized (Reg Step 3) to either continue or discontinue the assigned treatment. Patients are treated for up to 7 years from Step 2 reg and followed for up to 15 years.

    TRIAL NUMBER: COVID-19 Biospecimen

    Title: COVID-19 Biospecimen Collection

    Purpose:

    TRIAL NUMBER: EA8171

    Title: EA8171:Multiparametric MRI (mpMRI) for Preoperative Staging and Treatment Planning for Newly-Diagnosed Prostate Cancer

    Purpose: This phase II trial studies how well multiparametric magnetic resonance imaging (MRI) works in evaluating cancer stage and helping treatment planning in patients with prostate cancer. Multiparametric MRI may be useful for evaluating the type of cancer in finding aggressive disease.

    TRIAL NUMBER: NRG-GU002

    Title: NRG-GU002: PHASE II-III TRIAL OF ADJUVANT RADIOTHERAPY AND ANDROGEN DEPRIVATION FOLLOWING RADICAL PROSTATECTOMY WITH OR WITHOUT ADJUVANT DOCETAXEL

    Purpose: This randomized phase II/III trial studies docetaxel, antiandrogen therapy, and radiation therapy to see how well it works compared with antiandrogen therapy and radiation therapy alone in treating patients with prostate cancer that has been removed by surgery. Androgen can cause the growth of prostate cells. Antihormone therapy may lessen the amount of androgen made by the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving antiandrogen therapy and radiation therapy with or without docetaxel after surgery may kill any remaining tumor cells.

    TRIAL NUMBER: NRG-GU008

    Title: RANDOMIZED PHASE III TRIAL INCORPORATING ABIRATERONE ACETATE WITH PREDNISONE AND APALUTAMIDE AND ADVANCED IMAGING INTO SALVAGE TREATMENT FOR PATIENTS WITH NODE-POSITIVE PROSTATE CANCER AFTER RADICAL PROSTATECTOMY

    Purpose:

    TRIAL NUMBER: S1802

    Title: S1802: Phase III Randomized Trial of Standard Systemic Therapy (SST) versus Standard Systemic Therapy plus Definitive treatment (surgery or radiation) of the primary tumor in Metastatic Prostate Cancer

    Purpose: This phase III trial studies how well standard systemic therapy with or without definitive treatment (prostate removal surgery or radiation therapy) works in treating participants with prostate cancer that has spread to other places in the body. Addition of prostate removal surgery or radiation therapy to standard systemic therapy for prostate cancer may lower the chance of the cancer growing or spreading.

    TRIAL NUMBER: A031801

    Title: A PHASE II RANDOMIZED TRIAL OF RADIUM-223 DICHLORIDE AND CABOZANTINIB IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA WITH BONE METASTASIS (RADICAL)

    Purpose:

    Primary Outcome Measures :
    1. Symptomatic skeletal event (SSE)-free survival (FS) [ Time Frame: From the date of randomization to the date of the earliest occurrence of SSE or death from any cause, assessed up to 5 years ]
      SSE-FS distribution will be estimated using the method of Kaplan-Meier by treatment arm. Comparison between the two arms will be performed using a one-sided log-rank test and one-sided p-value less than 0.025 will indicate that the experimental arm is superior to the control arm. SSE-FS will be censored at the date of last SSE assessment for those alive and SSE free. Hazard ratio (experimental over control arm) as well as two-sided 90% confidence interval (CI) for treatment will be estimated using the stratified Cox proportional hazard model with a single treatment covariate.


    Secondary Outcome Measures :
    1. Incidence of adverse events [ Time Frame: Up to 5 years ]
      Will be determined using Common Terminology Criteria for Adverse Events version 5.0. Adverse events will be summarized and compared between arms using chi-square or fisher exact tests as appropriate.

    2. SSE-FS [ Time Frame: From randomization to the date of SSE or death due to any cause, whichever comes first, assessed up to 5 years ]
      Will be estimated with the Kaplan Meier methodology. Comparison between arms or between predefined groups will be conducted using the log-rank test.

    3. Progression-free survival [ Time Frame: From randomization to time of radiographic progression or death due to any cause, whichever occurs first, assessed up to 5 years ]
      Radiographic progression will be defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Will be estimated with the Kaplan Meier methodology. Comparison between arms or between predefined groups will be conducted using the log-rank test.

    4. Overall survival [ Time Frame: From randomization to the date of death due to any cause, assessed up to 5 years ]
      Will be estimated with the Kaplan Meier methodology. Comparison between arms or between predefined groups will be conducted using the log-rank test. Patients who are alive will be censored at last follow up date.

    5. Time to first SSE [ Time Frame: From randomization to the date of first SSE or death due to any cause, assessed up to 5 years ]
      Will be determined in each treatment. The median estimate to first SSE-FS will be calculated.

    6. Overall response rate (ORR) [ Time Frame: Up to 5 years ]
      Will be defined by RECIST version 1.1. Number and proportion of patients achieving ORR (by RECIST) will be summarized with two-sided 90% CI by treatment arm; comparison between arms will be conducted using chi-square or Fisher's exact test as appropriate.

    TRIAL NUMBER: S1931

    Title: Phase III Trial of Immunotherapy-Based Combination Therapy With or Without Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma (PROBE Trial)

    Purpose: This phase III trial compares the effect of adding surgery to a standard of care immunotherapy-based drug combination versus a standard of care immunotherapy-based drug combination alone in treating patients with kidney cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, pembrolizumab, and avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Surgery to remove the kidney, called a nephrectomy, is also considered standard of care; however, doctors who treat kidney cancer do not agree on its benefits. It is not yet known if the addition of surgery to an immunotherapy-based drug combination works better than an immunotherapy-based drug combination alone in treating patients with kidney cancer.

    TRIAL NUMBER: A031501

    Title: PHASE III RANDOMIZED ADJUVANT STUDY OF MK-3475 (PEMBROLIZUMAB) IN MUSCLE INVASIVE AND LOCALLY ADVANCED UROTHELIAL CARCINOMA (AMBASSADOR) VERSUS OBSERVATION

    Purpose: Primary Outcome Measures: Disease-free survival [ Time Frame: From randomization to the first metastatic recurrence (presence of any recurrent disease), or death, whichever occurs first, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.
    Overall survival [ Time Frame: From randomization to the date of death from any cause, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.

    Secondary Outcome Measures: Disease-free survival in PD-L1 positive and negative patients [ Time Frame: From randomization to the first metastatic recurrence (presence of any recurrent disease), or death, whichever occurs first, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.
    Overall survival in PD-L1 positive and negative patients [ Time Frame: From randomization to the date of death from any cause, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.

    Estimated Enrollment: 739 Actual Study Start Date: September 21, 2017 Estimated Study Completion Date: February 28, 2019 Estimated Primary Completion Date: February 28, 2019 (Final data collection date for primary outcome measure)

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    TRIAL NUMBER: EA2176

    Title: A Randomized Phase III Study of Immune Checkpoint Inhibition with Chemotherapy in Treatment-Naïve Metastatic Anal Cancer Patients

    Purpose:

    Primary Outcome Measures :
    1. Progression-free survival [ Time Frame: Up to 2 years ]
      Defined as the first of progressive disease or death due to any cause. Analyzed using a stratified two-sided overall 0.05 level log-rank test. Will utilize standard Eastern Cooperative Oncology Group -American College of Radiology Imaging Network interim monitoring for efficacy evaluation.


    Secondary Outcome Measures :
    1. Objective response rate (ORR) [ Time Frame: Up to 2 years ]
      ORR is the ratio of the number of patients with a complete response or partial response, as defined by Response Evaluation Criteria in Solid Tumors version 1.1, to the total number of treated patients.

    2. Overall survival [ Time Frame: Time between treatment randomization and death by any cause, assessed up to 2 years ]
      Evaluated by a stratified log-rank test, and using a two-sided 0.05 level Cochran Mantel-Haenzel.

    3. Incidence of adverse events [ Time Frame: Up to 2 years ]
      Analyses of toxicity will be via frequency tabulations and percentages by worst degree of toxicity and comparisons will be done via chi-square or Fisher's exact tests as appropriate.

    TRIAL NUMBER: A071701

    Title: Genomically-Guided Treatment Trial in Brain Metastases

    Purpose:

    Primary Outcome Measures :
    1. Objective response rate in the brain [ Time Frame: Up to 5 years ]
      Assessed per Response Assessment in Neuro-Oncology (RANO) criteria for brain metastases. The response rate is defined as the number of patients who have achieved complete response (CR) or partial response (PR) per RANO for brain metastases criteria during treatment with CDK, PI3K, or NTRK/ROS inhibitors divided by total number of evaluable patients. The response rate and associated exact confidence interval will be estimated within each cohort defined by the targeted agent and histology.


    Secondary Outcome Measures :
    1. Systemic response for extracranial disease [ Time Frame: Up to 5 years ]
      Assessed with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Will be estimated using the systemic response rate (SRR) - where SRR is defined as the number of evaluable patients achieving a response (PR or CR per RECIST 1.1) during treatment with study therapy divided by the total number of evaluable patients. Point estimates will be generated for systemic response rates within each cohort with corresponding 95% binomial confidence intervals.

    2. Clinical benefit rate for central nervous system (CNS) [ Time Frame: Up to 5 years ]
      Evaluated by Response Assessment in Neuro-Oncology (RANO) criteria. Will be estimated as the number of evaluable patients achieving stable disease (SD), partial response (PR), or complete response (CR) as their best objective response during treatment with protocol therapy divided by the total number of evaluable patients. Point estimates will be generated for clinical benefit rates within each cohort with corresponding 95% binomial confidence intervals.

    3. Clinical benefit rate for extracranial disease [ Time Frame: Up to 5 years ]
      Assessed by Response Evaluation Criteria in Solid Tumors (RECIST). Will be estimated as the number of evaluable patients achieving stable disease (SD), partial response (PR), or complete response (CR) as their best objective response (per RECIST for extracranial disease) during treatment with protocol therapy divided by the total number of evaluable patients. Point estimates will be generated for clinical benefit rates within each cohort with corresponding 95% binomial confidence intervals.

    4. Duration of response for brain metastases [ Time Frame: From the time measurement criteria are met for CR or PR for brain metastases until the first date that progressive CNS disease or death is documented, assessed up to 5 years ]
      Duration of response for brain metastases is defined for all evaluable patients who have achieved a confirmed response as the time from the date at which the patient's objective status for brain metastases is first noted to be a CR or PR (per Response Assessment in Neuro-Oncology [RANO] for brain metastases) to the date of the earliest progressive CNS disease is documented or death. The median and 95% confidence intervals will be estimated using the Kaplan-Meier estimator. No formal comparison will be made among the cohorts.

    5. Duration of response for extracranial disease [ Time Frame: From the time measurement criteria are met for CR or PR for extracranial disease until the first date that progressive disease for extracranial disease or death is documented, assessed up to 5 years ]
      Duration of response for extracranial disease is defined for all evaluable patients who have achieved a confirmed response as the time from the date at which the patient's objective status for extranial disease is first noted to be a CR or PR (per RECIST1.1) to the date of the earliest progression (PD) for extracranial disease is documented or death. The median and 95% confidence intervals will be estimated using the Kaplan-Meier estimator. No formal comparison will be made among the cohorts.

    6. Progression-free survival (PFS) - intracranial [ Time Frame: From first day of study treatment to the earliest date documentation of intracranial disease progression or death from any cause, assessed up to 5 years ]
      Intracranial PFS is defined as the time from the first day of study treatment to the earliest date of intracranial disease progression (per RANO for brain metastases) or death from any cause, whichever comes first. The median and 95% confidence intervals will be estimated using the Kaplan-Meier estimator. No formal comparison will be made among the cohorts.

    7. Progression-free survival (PFS) - extracranial [ Time Frame: From the first day of study treatment to the earliest date of documentation of extracranial disease progression or death from any cause, assessed up to 5 years ]
      Extracranial PFS is defined as the time from the first day of study treatment to the earliest date of extracranial disease progression (per RECIST1.1) or death from any cause, whichever comes first. The median and 95% confidence intervals will be estimated using the Kaplan-Meier estimator. No formal comparison will be made among the cohorts.

    8. Site of first progression [ Time Frame: Up to 24 months ]
      The site of first progression will be estimated descriptively within each cohort within 12 and 24 months after starting protocol treatment. The first progression is defined as the first documented central nervous system (CNS) progression per Response Assessment in Neuro-Oncology (RANO) or extracranial progression per Response Evaluation Criteria in Solid Tumors (RECIST), whichever occurs first. The percentage of extracranial progression at first progression within 12 and 24 months after starting protocol treatment will be estimated as number of patients who experience the first progression which is extracranial progression divided by number of patients who are still at risk up to 12 and 24 months, respectively.

    9. Overall survival [ Time Frame: From the first day of study treatment to death due to any cause, assessed up to 5 years ]
      Overall survival is defined as the time from the first day of study treatment to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. No formal comparison will be made among the cohorts.

    10. Incidence of adverse events [ Time Frame: Up to 5 years ]
      Assessed per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, toxicity is defined as adverse events that are classified as possibly, probably, or definitely related to study treatment. Toxicities will be evaluated via the ordinal CTCAE standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by patient and treatment cohort will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of the analysis. No formal comparison will be made among the cohorts.

    TRIAL NUMBER: CG01 GBM

    Title: Standard Chemotherapy versus Chemotherapy Chosen by Cancer Stem Cell Chemosensitivity Testing in the Management of Patients with Recurrent Glioblastoma Multiforme (GBM)

    Purpose:

    The purpose of this clinical study is to confirm the utility of chemosensitivity tumor testing on cancer stem cells (ChemoID) as a predictor of clinical response in poor prognosis malignant brain tumors such as recurrent glioblastoma (GBM).

    This study is designed as a parallel group randomized controlled clinical trial to determine if recurrent Glioblastoma (GBM) patients treated with drugs predicted by the ChemoID assay will have better outcomes than patients treated with standard-of-care control therapy chosen by the Physician.

    Upon obtaining informed consent, all eligible participants affected by recurrent GBM will have a tumor biopsy to undergo ChemoID drug response testing with multiple FDA-approved chemotherapeutic agents.

    Eligible participants will be randomized to a standard treatment arm with control treatment (chemotherapy chosen by the Physician from a provided list), or to a study arm of FDA-approved drugs selected by the ChemoID drug response assay.

    TRIAL NUMBER: Southeastern Study of Cancer and the Environment

    Title: Southeastern Study of Cancer and the Environment

    Purpose: STUDY PURPOSE - The purpose of the research is to provide new information on genetic and environmental risk factors for adult-onset glioma and meningioma. Such information is relevant to prevention and treatment. STUDY DESIGN – The study is a multi-institutional, clinic-based case-control study of genetic and environmental risk factors for adult-onset brain tumors (glioma and meningioma). Cases (brain tumor patients) will be identified at leading brain tumor treatment centers and several neurosurgical/neuro-oncology practices in the southeastern US. Community controls will be identified by a survey research firm (SDR Sampling Services - Atlanta, Georgia) with individual matching on age, gender, zipcode and season of enrollment. The second control group, consisting of friends, relatives and other associates of the case, will be matched on age and gender.

    TRIAL NUMBER: WF-1801

    Title: A Single Arm, Pilot Study of Ramipril for Preventing Radiation-Induced Cognitive Decline in Glioblastoma (GBM) Patients Receiving Brain Radiotherapy

    Purpose: This study is to determine if an oral drug called Ramipril can lower the chance of memory loss in patients with glioblastoma getting chemoradiation. Patients will take Ramipril during chemoradiation and continue until 4 months post-treatment. Memory loss will be assessed using several neurocognitive tests throughout the duration of the study.

    TRIAL NUMBER: EA1151

    Title: Digital Tomosynthesis Mammography and Digital Mammography in Screening Patients for Breast Cancer

    Purpose: This randomized phase III trial studies digital tomosynthesis mammography and digital mammography in screening patients for breast cancer. Screening for breast cancer with tomosynthesis mammography may be superior to digital mammography for breast cancer screening and may help reduce the need for additional imaging or treatment.

    TRIAL NUMBER: EA1181

    Title: CompassHER2-pCR: PREOPERATIVE THP AND POSTOPERATIVE HP IN PATIENTS WHO ACHIEVE A PATHOLOGIC COMPLETE RESPONSE PART 1 COMPONENT OF: THE CompassHER2 TRIALS (COMPREHENSIVE USE OF PATHOLOGIC RESPONSE ASSESSMENT TO OPTIMIZE THERAPY IN HER2-POSITIVE BREAST CANCER)

    Purpose:

    Primary Outcome Measures :
    1. Recurrence-free survival (RFS) [ Time Frame: Up to 3 years after end of treatment ]
      Events include recurrence of ipsilateral invasive breast tumor, recurrence of locoregional invasive breast tumor, and distant recurrence. Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and estrogen receptor (ER) status. Greenwood method will be used to estimate the 95% confidence interval for 3-year rate.


    Secondary Outcome Measures :
    1. Invasive disease-free survival (IDFS) [ Time Frame: Up to 3 years after the end of treatment ]
      Events include recurrence of ipsilateral invasive breast tumor, recurrence of locoregional invasive breast tumor, distant recurrence, contralateral invasive breast cancer, and second primary non-breast invasive cancer (other than squamous or basal cell skin cancer). Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

    2. Distant disease-free survival (DDFS) [ Time Frame: Up to 3 years after the end of treatment ]
      Events include distant recurrence and second primary non-breast invasive cancer (other than squamous or basal cell skin cancer). Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

    3. Distant relapse-free survival (DRFS) [ Time Frame: U to 3 years after the end of treatment ]
      Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

    4. Recurrence-free interval (RFI) [ Time Frame: Up to 3 years after the end of treatment ]
      Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

    5. Overall survival (OS) [ Time Frame: From date of surgery until the date of death from any cause, assessed up to 3 years after the end of treatment ]
      Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

    6. Event-free survival (EFS) [ Time Frame: Up to 3 years after the end of treatment ]
      Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

    7. Incidence of adverse events (AEs) [ Time Frame: Up to 1 week after cycle 4 (all patients) and/or up to cycle 13 post-surgery (Arm A only) (each cycle is 21 days) ]
      Will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. All treatment-emergent and baseline adverse events and hematological/biochemical toxicities based on laboratory measurements, as well as drug related AEs, will be summarized by NCI CTCAE v5.0 worst grade. The incidence of deaths and treatment-emergent serious adverse events (defined as number of patients experiencing the AE divided by all treated patients) will be summarized using binominal proportions and binomial exact 95% confidence intervals. The incidence of adverse events leading to discontinuation of protocol therapy will be summarized and listed as well.

    TRIAL NUMBER: S1418

    Title: A Randomized, Phase III Trial to Evaluate the Efficacy and Safety of MK-3475 (Pembrolizumab) as Adjuvant Therapy for Triple Receptor-Negative Breast Cancer With ? 1 cm Residual Invasive Cancer or Positive Lymph Nodes (ypN+) After Neoadjuvant Chemotherapy

    Purpose: This randomized phase III trial studies how well pembrolizumab works in treating triple-negative breast cancer. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

    TRIAL NUMBER: S1703

    Title: S1703; Randomized Non-Inferiority Trial Comparing Overall Survival of Patients Monitored with Serum Tumor Marker Directed Disease Monitoring (STMDDM) versus Usual Care in Patients with Metastatic Hormone Receptor Positive Breast Cancer

    Purpose: To assess whether patients with HER-2 negative, hormone receptor positive, metastatic breast cancer who are monitored with serum tumor marker directed disease monitoring (STMDDM) have non-inferior overall survival compared to patients monitored with usual care.

    TRIAL NUMBER: S1706

    Title: A PHASE II RANDOMIZED TRIAL OF OLAPARIB (NSC-747856) ADMINISTERED CONCURRENTLY WITH RADIOTHERAPY VERSUS RADIOTHERAPY ALONE FOR INFLAMMATORY BREAST CANCER

    Purpose: Primary Outcome Measures : Invasive Disease-Free Survival (IDFS) [ Time Frame: Up to 8 years ] Time from date of registration to date of first invasive recurrence (local, regional or distant), second invasive primary cancer (breast or not), or death due to any cause. Patients last known to be alive who have not experienced recurrence or second primary cancer are censored at their last contact date. Analysis will be on an intent-to-treat basis and will estimate the survival endpoints using the product-limit method of Kaplan and Meier and will compare the time-to-event distributions using log-rank test statistics. Hazard ratios will be calculated from Cox regression analyses. Effect modification by the stratification variables will be tested as interactions with treatment and separate hazard ratios with 95% confidence intervals by major subgroups will be displayed in a forest plot to examine for consistency of the treatment effect over these subgroups. Secondary Outcome Measures : Locoregional Recurrence-Free Interval (Local Disease-Free Interval (LDFI)) [ Time Frame: Up to 8 years ] Time from date of registration to date of invasive local or regional recurrence. Patients last known to be alive without recurrence are censored at their last contact date. Patients with distant recurrence, second primary cancer or death are censored at the time of that event. A competing risk framework will be conducted separating out the event types of locoregional recurrence from distant recurrence and death. Hazard ratios will be calculated from Cox regression analyses. Effect modification by the stratification variables will be tested as interactions with treatment and separate hazard ratios with 95% confidence intervals by major subgroups will be displayed in a forest plot to examine for consistency of the treatment effect over these subgroups. Distant Relapse-Free Survival (Distant Recurrence-Free Survival) [ Time Frame: Up to 8 years ] Time from date of registration to date of invasive distant disease recurrence, second invasive primary cancer (breast or not) or death due to any cause. Patients last known to be alive who have not experienced disease recurrence, or second primary cancer are censored at their last contact date. Overall Survival [ Time Frame: Up to 8 years ] Time from date of registration to date of death due to any cause. Patients last known to be alive are censored at their last contact date.

    TRIAL NUMBER: Seattle Genetics SGNLVA-001

    Title: A phase 1, open-label, dose-escalation study to evaluate the safety and tolerability of SGN-LIV1A in patients with LIV-1-positive metastatic breast cancer

    Purpose: This study will examine the safety and tolerability of SGN-LIV1A in patients with metastatic breast cancer. Increasing doses of SGN-LIV1A will be given every 3 weeks alone or in combination with trastuzumab.

    TRIAL NUMBER: URCC 16070

    Title: Netupitant/Palonosetron Hydrochloride and Dexamethasone With or Without Prochlorperazine or Olanzapine in Improving Chemotherapy-Induced Nausea and Vomiting in Patients With Breast Cancer

    Purpose: This randomized phase III trial studies how well netupitant/palonosetron hydrochloride and dexamethasone with prochlorperazine or olanzapine work compared to netupitant/palonosetron hydrochloride and dexamethasone in improving chemotherapy-induced nausea and vomiting in patients with breast cancer. Antiemetic drugs, such as prochlorperazine and olanzapine, may help lessen nausea and vomiting in patients with breast cancer treated with chemotherapy.

    TRIAL NUMBER: WF 97116

    Title: Phase 3 Randomized Placebo Controlled Clinical Trial of Donepezil - WF 97116

    Purpose: This study is to compare the safety and effects of donepezil (Aricept) or if it decreases memory loss after receiving chemotherapy for breast cancer.

    TRIAL NUMBER: DCP-001

    Title: DCP-001, Use of a Clinical Trial Screening Tool to Address Cancer Health Disparities in the NCI Community Oncology Research Program (NCORP)

    Purpose: The protocol is not a scientific study; rather, a method to implement the screening tool and allow the collection and analyses of expanded data with informed consent. Investigators also enroll patients into NCI-treatment trials. The tool, based on a screening log successfully used within the NCI Community Cancer Centers Program (NCCCP), has been streamlined and integrated into the sites’ workflow by using OPEN. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. Also missing from the existing data is the context of care, within the communities themselves where most cancer and at risk of cancer patients receive care which is the focus of NCORP. The profile of patients accrued to NCI-sponsored clinical trials lacks both racial/ethnic and socioeconomic diversity. Accrued patients tend to be insured, highly educated and of higher socioeconomic means. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. NCORP's clinical trials portfolio includes cancer control, prevention, screening, symptom science, and cancer care delivery research.

    TRIAL NUMBER: DCP-002

    Title: DCP-002 Early Onset Malignancies Initiative (EOMI): Molecular profiling of Breast, Prostate, Colorectal, Liver, Kidney, and Multiple Myeloma among Racially and Ethnically Diverse Populations

    Purpose: The primary objective of the EOMI (Early Onset Malignancy Initiative) is to acquire tissue and blood, and other biospecimens for research purposes from tests performed for clinical care or for research indications on other research protocols to accelerate our understanding of the molecular basis of early onset cancers occurring in racial and/or ethnic minority populations through the application of genome analysis technologies, including large-scale genome sequencing and clinical data analysis.

    TRIAL NUMBER: ChemoID

    Title: STANDARD CHEMOTHERAPY VERSUS CANCER STEM CELL ASSAY DIRECTED CHEMOTHERAPY IN RECURRENT PLATINUM RESISTANT OVARIAN CANCER

    Purpose:

    Primary Outcome Measures :
    1. Objective response rate [ Time Frame: 24 months ]
      Objective response rate (ORR) as measured by RECIST version 1.1 criteria in recurrent EOC patients who have had ChemoID-guided treatment versus physician choice control treatment (chemotherapy chosen by the physician from the provided list).


    Secondary Outcome Measures :
    1. Progression Free Survival (PFS) [ Time Frame: 24 months ]
      Progression free survival (PFS) in patients with recurrent epithelial ovarian cancer (EOC) who receive standard of care treatment (chemotherapy chosen by the physician from the provided list) versus ChemoID drug response assay-directed chemotherapy.

    2. Duration of Response [ Time Frame: 24 months ]
      Duration of Response (DOR) in patients with recurrent epithelial ovarian cancer (EOC) who receive standard of care treatment (chemotherapy chosen by the physician from the provided list) versus ChemoID drug response assay-directed chemotherapy.

    3. CA125 levels [ Time Frame: 24 months ]
      Levels of CA125 in patients with recurrent epithelial ovarian cancer (EOC) who receive standard of care treatment (chemotherapy chosen by the physician from the provided list) versus ChemoID drug response assay-directed chemotherapy.

    4. Health-Related Quality of Life (HRQOL) [ Time Frame: 24 months ]
      Health-Related Quality of Life (HRQOL) measured to ChemoID-guided treatment selection vs. standard chemotherapy chosen by the physician using self-reported and validated questionnaires, addressing physical, psychological, emotional, and social issues.

    TRIAL NUMBER: GOG 0263

    Title: RANDOMIZED PHASE III CLINICAL TRIAL OF ADJUVANT RADIATION VERSUS CHEMORADIATION IN INTERMEDIATE RISK, STAGE I/IIA CERVICAL CANCER TREATED WITH INITIAL RADICAL HYSTERECTOMY AND PELVIC LYMPHADENECTOMY

    Purpose: PRIMARY OBJECTIVES:
    I. To determine if post-operative adjuvant chemoradiotherapy (CRT) can significantly improve recurrence-free survival (RFS) when compared to radiation therapy (RT) alone in patients with intermediate- risk factors stage I- IIA cervical cancer after treatment with radical hysterectomy.
    SECONDARY OBJECTIVES:
    I. To compare the overall survival (OS) of patients treated with these regimens.
    II. To assess differences in incidence and severity of regimen-attributed adverse events in these patients.
    III. To provide assessment of patient risk vs benefit (positive study only). IV. To determine whether post-operative adjuvant CRT improves the health- related quality-of-life compared to RT alone.
    V. To compare toxicity profiles with particular focus on treatment-related genitourinary, gastrointestinal, neurological, pain, and sexual adverse events in these patients.
    TERTIARY OBJECTIVES:
    I. To bank archival tumor tissue for research studies, including studies that evaluate the association between biomarkers, RFS, OS, and clinical-surgical- pathologic characteristics in patients treated with these regimens.
    II. To bank DNA from whole blood for research studies, including studies that evaluate associations between single nucleotide polymorphisms (SNPs), and measures of clinical outcome, including RFS, OS, and adverse events in patients treated with these regimens.
    OUTLINE: This is a multicenter study. Patients are stratified according to capillary-lymphovascular space involvement (positive vs negative), stromal invasion (deep vs middle vs superficial), radiotherapy modality (external- beam radiation therapy [EBRT] vs intensity-modulated radiation therapy [IMRT]), and cooperative group (KGOG vs GOG). Patients are randomized to 1 of 2 treatment arms.
    ARM I: Patients undergo pelvic EBRT or IMRT 5 days a week for 5.5 weeks.
    ARM II: Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in arm I. Treatment with cisplatin repeats every 7 days for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
    Patients complete questionnaires on smoking history, Functional Assessment of Cancer Therapy (FACT-G, Version 4), FACT-Neurotoxicity subscale, and the Brief Pain Inventory (BPI) at baseline and periodically during study.
    Tumor tissue and blood samples may be collected and banked for future biomarker and other analysis.
    After completion of study therapy, patients are followed up every 3 months for 2 years, and then every 6 months for 3 years.

    TRIAL NUMBER: Iovance Biotherapeutics C-145-04

    Title: A Phase 2, Multicenter Study to Evaluate the Efficacy and Safety Using Autologous Tumor Infiltrating Lymphocytes (LN-145) in Patients with Recurrent, Metastatic, or Persistent Cervical Carcinoma

    Purpose: Prospective, multicenter, single-arm, open label, interventional study evaluating adoptive cell therapy (ACT) with autologous tumor infiltrating lymphocytes (TIL) infusion (LN-145) followed by IL-2 after a non-myeloablative (NMA) lymphodepletion preparative regimen for the treatment of patients with recurrent, metastatic, or persistent cervical carcinoma

    TRIAL NUMBER: NRG-GY006

    Title: A Randomized Phase II Trial of Radiation Therapy and Cisplatin Alone or in Combination with Intravenous Triapine in Women with Newly Diagnosed Bulky Stage IB2, Stage II, IIIB, or IVA Cancer of the Uterine Cervix or Stage II-IVA Vaginal Cancer

    Purpose: This randomized phase II trial studies radiation therapy and cisplatin with triapine to see how well they work compared to the standard radiation therapy and cisplatin alone in treating patients with newly diagnosed stage IB2, II, or IIIB-IVA cervical cancer or stage II-IVA vaginal cancer. Radiation therapy uses high energy protons to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether radiation therapy and cisplatin are more effective with triapine in treating cervical or vaginal cancer.

    TRIAL NUMBER: NRG-GY019

    Title: A RANDOMIZED PHASE III, TWO-ARM TRIAL OF PACLITAXEL/CARBOPLATIN/MAINTENANCE LETROZOLE VERSUS LETROZOLE MONOTHERAPY IN PATIENTS WITH STAGE II-IV, PRIMARY LOW-GRADE SEROUS CARCINOMA OF THE OVARY OR PERITONEUM

    Purpose:

    Primary Outcome Measures :
    1. Progression-free survival (PFS) [ Time Frame: Time from the randomized treatment assignment to documentation of disease progression (Response Evaluation Criteria in Solid Tumors 1.1) or death from any cause, whichever comes first, assessed up to 8 years ]
      The PFS comparison will be assessed at the second interim and final analyses using a logrank test stratified by country and residual disease status. Estimates for the letrozole/letrozole (L/L) vs paclitaxel/carboplatin/letrozole (CT/L) hazard ratio and its confidence interval will be obtained using a stratified Cox proportional hazards model. Potential confounding factors, including the stratification factors, performance status and self-declared racial designation will be considered in a final exploratory model. A forest plot of treatment hazard ratios with confidence intervals within subgroups will also be reported. PFS will be characterized by treatment group with Kaplan-Meier plots and estimates of the median PFS.


    Secondary Outcome Measures :
    1. Incidence of adverse events (AE) [ Time Frame: Up to 8 years ]
      The nature, frequency and degree of toxicity will be tabulated at the System Organ Class and AE Term levels using Common Terminology Criteria for Adverse Events version 5.0. Each patient will be represented according the maximum grade observed for each term, within randomized treatment assignment. Tabulations will show the number and percentage of patients by maximum grade, within their randomized treatment assignment.

    2. Objective response rate (ORR) [ Time Frame: Up to 8 years ]
      Will be estimated as the binomial proportion of patients with best overall response of complete response (CR) or partial response (PR) among patients with measurable disease after cytoreductive surgery. Response rates and their 95% Wilson-Score confidence intervals will be estimated for each treatment arm, using the randomized treatment assignment. The odds-ratio for ORR in the L/L vs CT/L arms will be estimated from the multivariable logistic regression model adjusted for stratification factors.

    3. Duration of response [ Time Frame: Time from documentation of response under documentation of progression or death, which is observed first, assessed up to 8 years ]
      Will be defined among patients with best overall response of CR or PR. Comparison of response duration between the randomized treatment arms will be supported by Kaplan Meier methods, and the corresponding estimates for median duration and its 95% confidence intervals.

    4. Overall survival (OS) [ Time Frame: Time between randomization and death from any cause, assessed up to 8 years ]
      Differences in OS across the randomized treatment groups will be assessed using Kaplan Meier methods, with median time to death estimates and the corresponding 95% confidence intervals. The L/L vs CT/L hazard ratio will be estimated by a proportional hazards model stratified by the randomization stratification factors.

    5. Adherence to letrozole maintenance therapy [ Time Frame: At cycles 1, 6, and 12 ]
      Will be quantified as the mean rate of adherence (MRA), calculated as the proportion of product not returned divided by the number of days since the previous visit at which study products were dispensed. Currently, the letrozole is delivered in a 2.5 mg pill, and the recommended dose is 2.5 mg per day. This outcome will be computed for each treatment cycle (generally 21 days). The mean MRA will be compared between the randomized treatment groups using linear mixed model methods. The model will be specified with a random patient effect, and fixed effects for randomized treatment indicator, time (cycle number) and the interaction, with an adjustment for the protocol stratification factors. Primary interest is in the difference in mean (MRA) at cycles 1, 6 and 12 between the treatment group. The results will be reported as the estimated mean (MRA) and 95% confidence intervals for each treatment/time combination. Treatment differences within stratification factors may also be considered.

    TRIAL NUMBER: NRG-GY020

    Title: A Phase III Randomized Trial of Radiation +/- MK-3475 (Pembrolizumab) for Newly Diagnosed Early Stage High Intermediate Risk Mismatch Repair Deficient (dMMR) Endometrioid Endometrial Cancer

    Purpose: This phase III trial compares whether the addition of pembrolizumab to radiation therapy is more effective than radiation therapy alone in reducing the risk of cancer coming back (recurrence) in patients with newly diagnosed stage I-II endometrial cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. The addition of pembrolizumab to radiation treatment may be more effective than radiation treatment alone in reducing cancer recurrence.

    TRIAL NUMBER: RTOG-0724

    Title: PHASE III RANDOMIZED STUDY OF CONCURRENT CHEMOTHERAPY AND PELVIC RADIATION THERAPY WITH OR WITHOUT ADJUVANT CHEMOTHERAPY IN HIGH-RISK PATIENTS WITH EARLY-STAGE CERVICAL CARCINOMA FOLLOWING RADICAL HYSTERECTOMY

    Purpose: OBJECTIVES:
    Primary ?To determine if administering adjuvant systemic chemotherapy after chemoradiotherapy will improve disease-free survival compared to chemoradiotherapy alone in patients with high-risk early-stage cervical carcinoma found to have positive nodes and/or positive parametria after radical hysterectomy.
    Secondary ?To evaluate adverse events. ?To evaluate overall survival. ?To evaluate quality of life. ?To evaluate chemotherapy-induced neuropathy. ?To perform a post-hoc dose-volume evaluation between patients treated with standard radiotherapy and patients treated with intensity-modulated radiotherapy (IMRT) with respect to toxicity and local control. ?To collect fixed tissue samples to identify tumor molecular signatures that may be associated with patient outcomes, such as adverse events, disease-free survival, and overall survival. ?To collect blood samples to identify secreted factors from serum and plasma that may be associated with adverse events or outcome and to identify single nucleotide polymorphisms (SNPs) in genes from buffy coat that may be associated with a genetic predisposition to tumor formation itself or a response to cytotoxic therapy.
    OUTLINE: This is a multicenter study. Patients are stratified according to planned use of brachytherapy (no vs. yes), radiotherapy modality - [standard external beam radiotherapy (EBRT) vs. intensity-modulated radiotherapy (IMRT)], and radiotherapy dose (45 Gy vs. 50.4 Gy). Patients are randomized to 1 of 2 treatment arms. ?Arm I: Patients undergo standard EBRT or IMRT to the pelvis once daily 5 days a week for 5-6 weeks. Patients also receive concurrent cisplatin IV over 1 hour once weekly for 6 weeks.
    NOTE: Some patients may also undergo brachytherapy beginning within 7 days after completion of radiotherapy. ?Arm II: Patients receive chemoradiotherapy as in arm I. Beginning 4-6 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
    Quality of life is assessed by the Functional Assessment of Cancer Therapy - Gynecologic Oncology Group (FACT-GOG/NTX4), FACT-Cx, and FACIT-D questionnaires at baseline; at the completion of chemoradiotherapy; and then at 6, 12, and 24 months after completion of chemoradiotherapy.
    Blood and tissue samples may be collected for gene expression analysis by immuno-histochemistry (IHC) and for biomarker and polymorphism studies.
    After completion of study treatment, patients are followed up very 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

    TRIAL NUMBER: CITN-12

    Title: Phase I Study of MK-3475 (Pembrolizumab) in Patients with Human Immunodeficiency Virus (HIV) and Relapsed/Refractory or Disseminated Malignant Neoplasm

    Purpose: This phase I trial studies the side effects of pembrolizumab in treating patients with human immunodeficiency virus (HIV) and malignant neoplasms that have come back (relapsed), do not respond to treatment (refractory), or have distributed over a large area in the body (disseminated). Monoclonal antibodies, such as pembrolizumab, may block tumor or cancer growth in different ways by targeting certain cells. It may also help the immune system kill cancer cells.

    TRIAL NUMBER: EA3132

    Title: EA3132:Phase II Randomized Trial of Radiotherapy with or Without Cisplatin for Surgically Resected Squamous Cell Carcinoma of the Head and Neck (SCCHN) with TP53 Sequencing

    Purpose: This phase II trial studies how well radiation therapy with or without cisplatin works in treating patients with stage III-IVA squamous cell carcinoma of the head and neck who have undergone surgery. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known if radiation therapy is more effective with or without cisplatin in treating patients with squamous cell carcinoma of the head and neck.

    TRIAL NUMBER: Iovance Biotherapeutics C-145-03

    Title: A Phase 2, Multicenter Study to Evaluate the Efficacy and Safety of Autologous Tumor Infiltrating Lymphocytes (LN-145) for the Treatment of Patients with Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck

    Purpose: Prospective, multicenter, single-arm, open label, interventional study evaluating adoptive cell therapy (ACT) with autologous tumor infiltrating lymphocytes (TIL) infusion (LN-145) followed by IL-2 after a non-myeloablative (NMA) lymphodepletion preparative regimen for the treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck

    TRIAL NUMBER: A031704

    Title: PD-Inhibitor (Nivolumab) and Ipilimumab Followed by Nivolumab Vs. VEGF TKI Cabozantinib with Nivolumab: A Phase III Trial in Metastatic Untreated REnal Cell CancEr [PDIGREE]

    Purpose: This phase III trial studies how well nivolumab and ipilimumab, followed by nivolumab versus cabozantinib and nivolumab, work in treating patients with renal cell cancer that is untreated and has spread to other parts of the body. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cabozantinib, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known how well cabozantinib and nivolumab work in treating patients with untreated renal cell cancer that has spread to other parts of the body.

    TRIAL NUMBER: EA8143

    Title: EA8143:A Phase 3 RandOmized Study Comparing PERioperative Nivolumab vs. Observation in Patients with Localized Renal Cell Carcinoma Undergoing Nephrectomy (PROSPER RCC)

    Purpose: The purpose of this study is to compare any good and bad effects of using nivolumab (also known as OPDIVO®), before and after the kidney cancer surgery to using the usual approach of surgically removing the kidney cancer followed by standard post-operative follow-up and monitoring. Nivolumab is a drug that may help stimulate your immune system to attack any cancer cells that may remain after surgery. The addition of nivolumab to the usual surgery could prevent your cancer from returning but it could also cause side effects. This research study will allow researchers to find out whether this different treatment is better, the same, or worse than the usual treatment for kidney cancer that has been removed but is at risk for coming back The study drug, nivolumab, is already FDA-approved for patients who have kidney cancer that has spread outside of the kidney to other organs or lymph nodes. The use of nivolumab in this study is investigational (not approved by the FDA) for your early stage of cancer where we do not know for sure if the disease has spread outside of the kidney. This research study will allow the researchers to know whether this different approach is better, the same, or worse than the usual approach. To be better, the study drug should improve how long you are able to live without any signs or symptoms of your cancer compared to the usual approach

    TRIAL NUMBER: A151216

    Title: Genetic Testing For Patients with Resectable or Resected Lung Cancer: Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST)

    Purpose: PRIMARY OBJECTIVES:
    I. To centrally genotype resected lung adenocarcinomas for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements to facilitate accrual to randomized adjuvant studies.
    II. To obtain clinically annotated tumor tissue and patient-matched non-malignant deoxyribonucleic acid (DNA) from peripheral blood, as well as detailed epidemiologic and clinical follow-up data, to allow clinically annotated advanced genomic analyses in concert with the National Cancer Institute (NCI) Center for Cancer Genomics (CCG).
    SECONDARY OBJECTIVES:
    I. To characterize the natural history of EGFR and ALK wild-type lung cancers to allow subsequent development of targeted therapies against genotype-defined sub-populations in the adjuvant and recurrent settings.
    II. To cross-validate local genotyping assays for EGFR and ALK with a central reference standard.
    TERTIARY OBJECTIVES:
    I. To study the genomic evolution of lung cancers by comparing genomic characteristics at resection and at recurrence.
    OUTLINE:
    Patients undergo collection of blood and tissue samples for EGFR and ALK testing via direct sequencing and fluorescence in situ hybridization (FISH). Patients that have had surgery prior to pre-registration will submit samples from the previous surgery for testing.
    After completion of study, patients that are not enrolled on either A081105 or E4512 are followed up every 6 months for 5 years.

    TRIAL NUMBER: A171901

    Title: Older Non-Small Cell Lung Cancer Patients (>/= 70 Years of Age) Treated With First-Line MK-3475 (Pembrolizumab)+/- Chemotherapy (Oncologist's/Patient's Choice)

    Purpose: This trial studies the side effects of pembrolizumab with or without chemotherapy in treating patients with stage IV non-small cell lung cancer that has come back (recurrent) and has spread to other places in the body (advanced). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as pemetrexed and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab with or without chemotherapy may shrink the tumor in older patients with non-small cell lung cancer.

    TRIAL NUMBER: E4512

    Title: A Phase III Double-Blind Trial for Surgically Resected Early Stage Non-Small Cell Lung Cancer: Crizotinib versus Placebo for Patients with Tumors Harboring the Anaplastic Lymphoma Kinase (ALK) Fusion Protein

    Purpose: PRIMARY OBJECTIVES:
    I. To evaluate whether adjuvant therapy with crizotinib will result in improved overall survival (OS) over placebo for patients with stage IB >= 4 cm, II and IIIA, anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) following surgical resection.
    SECONDARY OBJECTIVES:
    I. To evaluate and compare disease-free survival (DFS) associated with crizotinib and placebo.
    II. To evaluate the safety profile of crizotinib when given in the adjuvant therapy setting.
    III. To collect tumor tissue and blood specimens for future research.
    OUTLINE: Patients are randomized to 1 of 2 treatment arms.
    ARM A: Patients receive crizotinib orally (PO) twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
    ARM B: Patients receive placebo PO BID on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
    After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly for 5 years.

    TRIAL NUMBER: EA5163

    Title: EA5163/S1709 INSIGNA : A Randomized, Phase III Study of Firstline Immunotherapy Alone or in Combination with Chemotherapy in Induction/Maintenance or Postprogression in Advanced Nonsquamous Non-Small Cell Lung Cancer (NSCLC) with Immunobiomarker SIGNature-Driven Analysis

    Purpose: Primary Outcome Measures : Overall survival (OS) [ Time Frame: From randomization to death from any cause, assessed up to 5 years post treatment ] OS distributions will be estimated using the Kaplan-Meier method.

    Secondary Outcome Measures : Progression-free survival (PFS) [ Time Frame: From randomization to documented disease progression or death from any cause, assessed up to 5 years post treatment ] PFS distributions will be estimated using the Kaplan-Meier method.
    Best objective response [ Time Frame: Up to 5 years post treatment ] Best objective response will be evaluated via Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
    Incidence of adverse events [ Time Frame: Up to 30 days post treatment ] Toxicities will be reported via the Common Terminology Criteria for Adverse Events (CTCAE) criteria version 5.0. Toxicity rates between arms in the overall population will be compared using Fisher's exact tests with a one-sided type I error rate of 1.25%; multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes.
    PD-L1 positivity [ Time Frame: At baseline ] PD-L1 positivity will be defined as >= 1% Tumor Proportion Score (TPS) for the purpose of enrollment onto the trial. Strongly PD-L1 positive is defined as >= 50% TPS; weakly positive is defined as 1% - 49% TPS.

    TRIAL NUMBER: LungMAP

    Title: LungMAP: A MASTER PROTOCOL TO EVALUATE BIOMARKER-DRIVEN THERAPIES AND IMMUNOTHERAPIES IN PREVIOUSLY-TREATED NON-SMALL CELL LUNG CANCER (Lung-MAP Screening Study)

    Purpose: 1.1 Primary Objective of the Master Protocol (LungMAP) The primary objective of this screening study is to test patient specimens to determine eligibility for participation in the biomarker-driven and non-matched sub-studies included within the Lung-MAP umbrella protocol. 1.2 Secondary Objectives a. Screening Success Rate Objective To evaluate the screen success rate defined as the percentage of screened patients that register for a therapeutic sub-study. Screen success rates will be evaluated for the total screened population and by the subset of patients screened following progression on previous therapy or pre-screened on current therapy. b. Translational Medicine Objectives 1. To evaluate circulating tumor DNA (ctDNA) and compare to the FMI Foundation tissue molecular profiling results in patients who submit a new biopsy for screening. 2. To establish a tissue/blood repository

    TRIAL NUMBER: NRG-LU005

    Title: Limited Stage Small Cell Lung Cancer (LS-SCLC): A Phase II/III Randomized Study of Chemoradiation Versus Chemoradiation Plus Atezolizumab

    Purpose: Primary Outcome Measures :
    Progression-free survival (PFS) (Phase II) [ Time Frame: Time from randomization to any documented progression or death due to any cause, whichever occurs first, assessed up to 5 years ] Progressive disease (PD) will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will compare the distributions of PFS between treatment arms using a one-sided stratified log-rank test in all randomized eligible patients. The rates at various timepoints (e.g., every 6 months after randomization) and medians of PFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95% confidence interval (CI) will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Results from an unstratified analysis will also be provided.
    Overall survival (OS) (Phase III) [ Time Frame: Time from randomization to the date of death due to any cause, assessed up to 5 years ] The primary hypotheses for the phase II and III portions will be evaluated by comparing arm 1 to arm 2 based on PFS (phase II) and OS (phase III) using a stratified log-rank test. Hazard ratios will be estimated using a stratified Cox regression model. Event rates over time will be estimated within each treatment group using the Kaplan-Meier method.

    Secondary Outcome Measures :
    PFS (phase III) [ Time Frame: Time from randomization to any documented progression or death due to any cause, whichever occurs first, assessed up to 5 years ] The primary hypotheses for the phase II and III portions will be evaluated by comparing arm 1 to arm 2 based on PFS (phase II) and OS (phase III) using a stratified log-rank test. Hazard ratios will be estimated using a stratified Cox regression model. Event rates over time will be estimated within each treatment group using the Kaplan-Meier method.
    Incidence of adverse events [ Time Frame: Up to 5 years ] For each patient, the maximum severity reported for both immune mediated and non-immune mediated adverse events will be used in the summaries. Adverse events will be summarized regardless of relationship to protocol treatment as assessed by the investigator. All adverse events, adverse events leading to withdrawal, interruption or modification of protocol treatment, Grade >= 3 adverse events, and serious adverse events will be summarized. Deaths and cause of death will be summarized. The rate of treatment-related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE, v.5.0) will be reported with the frequency and severity (e.g., type, grade, and attribution) by arm, the analysis will be performed at the time of both phase II and phase III (if applicable) primary endpoint analyses. All adverse events will be classified as either immune or non-immune mediated.
    Objective response rate (ORR) [ Time Frame: Up to 5 years ] Will be defined as the proportion of all randomized subjects whose best overall response (BOR) is either a complete response (CR) or partial response (PR) per RECIST 1.1 criteria. ORR will be compared using a two-sided 5% level Cochran-Mantel Haenszel (CMH) test stratified by the same stratification factors used for randomization. An associated odds ratio and 95% CI will be calculated. The ORR and its corresponding 95% exact CI will also be calculated by Clopper-Pearson for each treatment arm. The difference in ORR between the two treatment arms along with the two-sided 95% CI will be estimated using the following CMH method of weighting, adjusting for the stratification factors.
    Local control [ Time Frame: Up to 5 years ] Will be defined as freedom from local progression, in which a failure is defined as intrathoracic tumor progression by RECIST 1.1 criteria. Local control will be analyzed as competing risks data based on cause-specific hazards approaches, where deaths without local failure will be considered as a competing event and analyzed as "censoring" of local failure. The rates at various timepoints (e.g., every 6 months after randomization) and medians of PFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95% CI will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Results from an unstratified analysis will also be provided.
    Distant metastases-free survival (DMFS) [ Time Frame: Time between the date of randomization and the first date of documented distant metastases or death due to any cause, whichever occurs first, assessed up to 5 years ] Will compare the distributions of DMFS between treatment arms using a one-sided stratified log-rank test in all randomized eligible patients. The rates at various timepoints (e.g., every 6 months after randomization) and medians of DMFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95% CI will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Results from an unstratified analysis will also be provided.
    Quality of life (QoL) [ Time Frame: Up to 15 months after the end of the 4th cycle of chemotherapy ] Will be measured by the Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI). Fisher's exact test will be used to compare the proportions of patients experiencing clinically meaningful deterioration (CMD) between the two arms. FACT-TOI deterioration rates and associated 95% confidence interval will be calculated for each treatment group, based on all randomized subjects. Clopper-Pearson method will be used for calculating 95% CI. The deterioration rates of each arm will also be compared using the CMH test, stratified by histology. FACT-TOI at baseline and at each subsequent assessment, as well as their change from baseline will be summarized using descriptive statistics by treatment group as randomized. The scores at baseline and subsequent time points, as well the changes from baseline at each time point for each treatment group will be compared using the two-sample t-test.
    Quality-adjusted survival [ Time Frame: Up to 2 years ] Assessed using score from the 5-level EuroQol 5-dimensional questionnaire (EQ-5D-5L). Defined as the weighted sum of different time episodes added up to a total quality-adjusted life-year. Subjects' overall health state on a visual analog scale (VAS) at each assessment time point will be summarized using descriptive statistics by treatment group, as randomized. Proportion of subjects reporting problems for the five EQ-5D-5L dimensions at each assessment time point will be summarized by level of problem and by treatment group, as randomized. Percentages will be based on number subjects assessed at assessment time point. Subjects' overall health state on a visual analog scale (EQ-VAS) at each assessment time point will be summarized using descriptive statistics by treatment group, as randomized. Proportion of subjects reporting problems for the five EQ-5D dimensions at each assessment time point will be summarized by level of problem and by treatment group, as randomized.
    Level of fatigue [ Time Frame: Up to 2 years ] Will be measured by the Patient-Reported Outcomes Measurement Information System (PROMIS). Baseline and PROMIS at each subsequent assessment, as well as their change from baseline will be summarized using descriptive statistics by treatment group as randomized. The change from baseline to subsequent timepoints may be compared between treatment arms using a t-test, or Wilcoxon test if the data is non-normal.
    Blood based tumor mutational burden (bTMB) and tissue-based tumor mutational burden (tTMB) [ Time Frame: Up to 5 years ] Correlation with clinical outcomes will be done by summarizing the statistical power to detect interaction effects (ratio of hazard ratios) of 0.33 when the marker positive prevalence is 20%, at 2-sided significance level of 0.05.

    Other Outcome Measures:
    Patient-reported symptomatic toxicities [ Time Frame: Up to 15 months after completion of chemoradiation therapy ] Will be measured by Patient Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE). For each symptom and each domain (i.e., frequency, severity, and interference), counts and frequencies will be summarized for the worst score experienced by the patient by treatment arm.

    TRIAL NUMBER: S1827

    Title: A RANDOMIZED PHASE III TRIAL OF MRI SURVEILLANCE WITH OR WITHOUT PROPHYLACTIC CRANIAL IRRADIATION (PCI) IN SMALL-CELL LUNG CANCER

    Purpose:

    Primary Outcome Measures :
    1. Overall survival (OS) [ Time Frame: From the date of registration to date of death due to any cause, assessed up to 2 years after randomization ]
      Will evaluate OS with magnetic resonance imaging (MRI) surveillance alone and MRI surveillance combined with prophylactic cranial irradiation (PCI) for the treatment of small cell lung cancer (SCLC).


    Secondary Outcome Measures :
    1. Cognitive failure-free survival (CFFS) [ Time Frame: Baseline to first neurocognitive failure CF or death due to any cause, assessed up to 12 months after randomization ]
      The comparison of CFFS up to 12 months between the arms will be done using a 1-sided 5% level log-rank test.

    2. CFFS rate [ Time Frame: Baseline to first neurocognitive failure CF or death due to any cause, assessed at 90, 180, 270, 360, 540, and 720 days after randomization ]
      There will be a comparison of the CFFS rates between the arms at each of the assessment times and the cumulative incidence of cognitive failure, evaluating death as a competing risk. The CFFS rates at the landmark times will be estimated using the method of Kaplan-Meier and the difference in rates will be evaluated using a 90% confidence interval using Greenwood?s formula.

    3. Cumulative incidence of cognitive failure [ Time Frame: Neurocognitive function test will be assessed at 90, 180, 270, 360, 540, and 720 days after randomization ]
      The cumulative incidence of cognitive failure in the presence of the competing risk of death will be estimated used the method of Fine and Gray.

    4. OS in an "as-treated" analysis [ Time Frame: From the date of registration to date of death due to any cause, assessed up to 2 years after randomization. Patients will be seen at day 90, 180, 270, 360, 540, and 720 ]
      The comparison of OS in the ?as-treated? analysis will be done as described for the primary analysis, however patients will be categorized per treatment received (patients who do not accept their randomized assignment will be analyzed per treatment received). The number of patients not accepting the randomized assignment will also be summarized.

    5. Brain metastases-free survival (BMFS) [ Time Frame: Up to 2 years after randomization. Patients will have MRI on day 90, 180, 270, 360, 540, and 720 ]
      This will be estimated using the method of Kaplan-Meier and comparisons will be done using a log-rank test at the 1-sided 0.05 level. Hazard ratios and associated confidence intervals will be estimated using a Cox Proportional hazards model. Confidence intervals for medians will be estimated using the method of Brookmeyer-Crowley.

    6. Incidence of adverse events [ Time Frame: Up to 2 years after randomization. Patients will be assessed for adverse event after PCI (for patients on PCI + MRI arm) and at month 3 (all patients) ]
      Binary proportions and associated confidence intervals will be estimated.

    TRIAL NUMBER: A051701

    Title: RANDOMIZED PHASE II/III STUDY OF VENETOCLAX (ABT 199) PLUS HEMOIMMUNOTHERAPY FOR MYC/BCL2 DOUBLE-HIT AND DOUBLE EXPRESSING LYMPHOMAS

    Purpose:

    Primary Outcome Measures :
    1. Progression-free survival (PFS) (phase II) [ Time Frame: From randomization date until the earlier of disease progression, or death from any cause, assessed up to 10 years ]
      Will be compared between the experimental and control arms using a stratified log-rank test. If one of the strata has 0 events or there are numerical issues due to the sparseness of the date within strata, an unstratified log-rank test will be used. The Kaplan-Meier method will be used to estimate PFS distributions. One-year PFS estimates, medians, and corresponding hazard ratios will be provided with 95% confidence intervals for each of the double hit lymphoma (DHL) and double expressing lymphoma (DEL) cohorts.

    2. PFS (phase III) [ Time Frame: At 24 months ]
      Will be compared between the experimental and control arms using a Mantel-Haenszel test without a continuity correction. In the event that there is censoring prior to 24 months, a test based on the complementary log-log transformation of Kaplan-Meier estimates will compare PFS at 24 months between experimental and control arms. Two-year PFS estimates, medians, and corresponding hazard ratios will be provided with 95% confidence intervals overall.


    Secondary Outcome Measures :
    1. Overall survival (OS) (phase III) [ Time Frame: From randomization date until death from any cause, assessed up to 10 years ]
      Using a modified intent-to-treat approach, all eligible patients who are centrally confirmed as having a DHL/DEL subtype will be considered evaluable and included in the analysis of the key secondary endpoint in the arm to which they were randomized and under the centrally designated subtype. OS will be compared between the experimental and control arms using a stratified log-rank test. Two-year OS estimates, medians, and corresponding hazard ratios will be provided with 95% confidence intervals overall.

    2. Event-free survival [ Time Frame: From randomization date until the earlier of non-protocol lymphoma therapy, disease progression, or death from any cause, assessed up to 10 years ]
      Will be compared between the experimental and control arms using a log-rank test. Estimated using Kaplan-Meier method by arm and lymphoma subtype.

    3. Response rate [ Time Frame: Up to 1 week after end of cycle 6 ]

      Response will be evaluated using the Lugano criteria for lymphoma response. Best achieved response rate with the intervention will be determined, defined as the number of patients who attain a complete or partial response using positron emission tomography (PET)/computed tomography (CT) out of the total number of evaluable patients who are randomized.

      Response rates will be compared between arms using a chi-square test once all patients on the study have been evaluated for response. Response rates will be estimated by arm and lymphoma subtype with 95% confidence intervals. Logistic regression will be used in a multivariable analysis to identify baseline variables associated with response.


    4. Inconsistency of local and central results for DEL or DHL status [ Time Frame: Until last patient is registered, up to month 57 ]
      Estimated by the number of patients with a local determination of DHL but not central determination of DHL (i.e., positive for DEL or negative for both DHL and DEL) or local determination of DEL but not central determination of DEL (i.e., positive for DHL or negative for both DHL and DEL) divided by the total number of registered patients with adequate material/tissue for central review.

    TRIAL NUMBER: 10231

    Title: NCORP TISSUE PROCUREMENT PROTOCOL: AN NCI CANCER MOONSHOT(SM) STUDY

    Purpose: Primary Outcome Measures : Obtaining tumor tissue and blood specimens [ Time Frame: Up to 2 years ] Will obtain tumor tissue and blood specimens for biobanking and to store tissues, blood, and nucleic acids for future research, including the study of matched pre and post-treatment tumor biopsies to elucidate mechanisms of resistance. Cases will be grouped according to histology and/or treatment. Secondary Outcome Measures : Tumor tissues storage in the Biopathology Center (BPC) at Nationwide Children?s Hospital (NCH) (Biorepository) [ Time Frame: Up to 2 years ] Genomic analysis [ Time Frame: Up to 2 years ] Will perform genomic studies, including a pan-cancer gene panel, and contribute molecular data to the genomic data commons. Biospecimen Retention: Samples With DNA Blood, tissue

    TRIAL NUMBER: EAY131

    Title: EAY131: Molecular Analysis for Therapy Choice (NCI-MATCH)

    Purpose: This phase II trial studies how well treatment that is directed by genetic testing works in patients with solid tumors or lymphomas that have progressed following at least one line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment which targets their tumor's particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors or lymphomas.

    TRIAL NUMBER: NCICOVID

    Title: NCI COVID-19 in Cancer Patients Study (NCCAPS): A Longitudinal Natural History Study

    Purpose: This study collects blood samples, medical information, and medical images from patients who are being treated for cancer and have a positive test for SARS CoV-2, the new coronavirus that causes the disease called COVID-19. Collecting blood samples, medical information, and medical images may help researchers determine how COVID-19 affects the outcomes of patients undergoing cancer treatment and how having cancer affects COVID-19.

    TRIAL NUMBER: S1609

    Title: SWOG 1609: DART: Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors Treatment with Ipilimumab and Nivolumab for Rare Cancers

    Purpose: Both Ipilimumab and Nivolumab have already been FDA-approved to treat other cancers. However, Ipilimumab and Nivolumab are investigational and not FDA-approved for use in combination in treating rare cancers or cancers of unknown primary origin.

    TRIAL NUMBER: S1714

    Title: A PROSPECTIVE OBSERVATIONAL COHORT STUDY TO DEVELOP A PREDICTIVE MODEL OF TAXANE-INDUCED PERIPHERAL NEUROPATHY IN CANCER PATIENTS

    Purpose: 1.1 Primary Objective a. To develop and validate a clinical risk prediction model using clinical factors for the development of peripheral neuropathy in patients receiving taxane-based chemotherapy regimens. 1.2 Secondary Objectives a. To examine patient-reported outcomes (PROs) and objective measures of chemotherapy induced peripheral neuropathy (CIPN) to better define the phenotype of peripheral neuropathy in this patient population. b. To assess the incidence of CIPN within one year in this patient population. c. To identify predictors of treatment dose reductions, delays, and discontinuations associated with CIPN symptoms in this patient population. 1.3 Other Objectives a. To collect serum and plasma samples for future testing for biomarker and mechanistic studies of CIPN.

    TRIAL NUMBER: A151804

    Title: Establishment of a National Biorepository to Advance Studies of Immune-Related Adverse Events

    Purpose: This trial collects research data and samples from patients who experience immunotherapy side effects to store for use in future research studies. Studying research data and samples from patients who experience immunotherapy side effects may help researchers better understand how to predict, prevent, and treat these side effects.

    TRIAL NUMBER: Advenchen AL3818-US-002

    Title: A Phase 1/2a Evaluation of the Safety and Efficacy of Adding AL3818, a Dual Receptor Tyrosine Kinase Inhibitor, to Standard Platinum-Based Chemotherapy in Subjects with Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma

    Purpose: This trial is a Phase 1b/2a trial designed to evaluate the safety and efficacy of adding oral AL3818 to standard platinum-based chemotherapy concurrently and continued as a maintenance therapy for up to 12 months.

    TRIAL NUMBER: A031501

    Title: PHASE III RANDOMIZED ADJUVANT STUDY OF MK-3475 (PEMBROLIZUMAB) IN MUSCLE INVASIVE AND LOCALLY ADVANCED UROTHELIAL CARCINOMA (AMBASSADOR) VERSUS OBSERVATION

    Purpose: Primary Outcome Measures: Disease-free survival [ Time Frame: From randomization to the first metastatic recurrence (presence of any recurrent disease), or death, whichever occurs first, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.
    Overall survival [ Time Frame: From randomization to the date of death from any cause, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.

    Secondary Outcome Measures: Disease-free survival in PD-L1 positive and negative patients [ Time Frame: From randomization to the first metastatic recurrence (presence of any recurrent disease), or death, whichever occurs first, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.
    Overall survival in PD-L1 positive and negative patients [ Time Frame: From randomization to the date of death from any cause, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.

    Estimated Enrollment: 739 Actual Study Start Date: September 21, 2017 Estimated Study Completion Date: February 28, 2019 Estimated Primary Completion Date: February 28, 2019 (Final data collection date for primary outcome measure)

    • East Jefferson General Hospital
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    TRIAL NUMBER: A031803

    Title: PHASE II TRIAL OF INTRAVESICAL GEMCITABINE AND MK-3475 (PEMBROLIZUMAB) IN THE TREATMENT OF PATIENTS WITH BCG- NRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER

    Purpose:

    Primary Outcome Measures :
    1. Complete response rate in the carcinoma in situ (CIS) subpopulation [ Time Frame: At 6 months ]
      A complete response, only for patients with a CIS component, is a cystoscopy without evidence of bladder tumor, negative biopsy (including directed biopsies to any suspicious areas and in addition random bladder biopsies including trigone, left lateral wall, right lateral wall, posterior bladder, dome of bladder, and the prostatic urethra in men) and negative cytology for high grade disease at 6 months (end of cycle 8, week 25).

    2. Event-free survival at 18 months [ Time Frame: From the date of study registration to the first documentation of an event or death whichever comes first, assessed up to 18 months ]
      EFS will be measure from the date of study registration to the first documentation of an event or death whichever comes first. For patients without a documented event and who are still alive, they will be censored at last disease assessment. For patients who start any subsequent ant-cancer therapy without any reported events will be censored at their last disease assessment. will be obtained with a Kaplan-Meier estimator (using the Greenwood formula to estimate the variance) for the entire 155 patient group consisting of patients with CIS, CIS with Ta/T1 or Ta or T1 disease. A 90% confidence interval will be generated for the 18-month EFS estimate.


    Secondary Outcome Measures :
    1. Incidence of adverse events [ Time Frame: Up to 5 years post treatment ]
      Adverse events will be assessed based on the National Cancer Institute (NCI) common toxicity criteria (Common Terminology Criteria for Adverse Events [CTACAE] version [v] 5.0).

    2. Duration of response (DOR) [ Time Frame: From the time a patient had a documented response that had been confirmed (the time would start at the time a response was first noted) until disease-progression, assessed up to 5 years ]
      Analysis will only include those patients with a confirmed response. Patients who are alive and without a documented progression at the time of analysis will be censored at the time of the last disease status evaluation. The Kaplan-Meier product-limit estimator will be used to estimate DOR, medians and 95% confidence intervals (CI).

    3. Progression-free survival (PFS) [ Time Frame: From the date of study registration to the date of progression or death due to any cause, whichever occurs first, assessed up to 5 years ]
      Surviving patients without any documented progressions will be censored at the date of last known contact. Progression will be defined as the development of muscle invasive bladder cancer or metastatic urothelial cancer (nodal and/or distant). The Kaplan-Meier product-limit estimator will be used to estimate PFS, medians and 95% CI.

    4. Overall survival (OS) [ Time Frame: From the date of study registration to date of death due to any cause, assessed up to 5 years ]
      Surviving patients will be censored at the date of last known contact. The Kaplan-Meier product-limit estimator will be used to estimate OS, medians and 95% CI.

    5. Cystectomy-free survival [ Time Frame: From the date of study registration to the date of cystectomy for all patients ]
      The Kaplan-Meier product-limit estimator will be used to estimate cystectomy-free survival, medians and 95% CI.

    6. Recurrence free survival (RFS) [ Time Frame: From the date of study registration to the first documentation of recurrence or death due to any cause, assessed up to 5 years ]
      Surviving patients without any documented recurrence will be censored at the date of last known contact. Recurrence will be defined as the development of high-grade bladder cancer for patients with a CIS component only and those without a CIS component. The Kaplan-Meier product-limit estimator will be used to estimate RFS, medians and 95% CI.

    TRIAL NUMBER: CITN-14

    Title: A Randomized Phase II Study of Atezolizumab (MPDL3280A) Plus Recombinant Human IL7 (CYT107) in Patients with Locally Advanced or Metastatic Urothelial Carcinoma

    Purpose: Primary Outcome Measures : Objective response rate (ORR) [ Time Frame: Up to 2 years ] ORR to be defined by complete response (CR) or partial response (PR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version (v.) 1.1. The Cochran Mantel Haenszel test will be conducted to compare ORR in the experimental arm (atezolizumab + CYT107) to the ORR in the control arm (atezolizumab monotherapy). A one-sided significance level of 0.10 will be considered for the test.

    Secondary Outcome Measures : Clinical benefit rate (CBR) measured by RECIST version (v.) 1.1 and immune-related (ir) RECIST [ Time Frame: Up to 2 years ] CBR is defined as the percentage of patients with advanced or metastatic cancer who have achieved CR, PR, and stable disease (SD) to a therapeutic intervention in clinical trials of anticancer agents. A two-sided test for a difference in proportions will be conducted to compare the CBR in the experimental arm to the CBR in the control arm. A two-sided significance level of 0.05 will be considered for the test. Will also assess CBR in patients stratified by PD-L1 expression levels in the tumor microenvironment, as assayed by Genentech.
    Progression-free survival (PFS) [ Time Frame: Up to 2 years ] PFS to be measured by RECIST v1.1 and irRECIST. PFS will be summarized using Kaplan-Meier estimates. Long-rank tests will be conducted for overall survival (OS) and PFS to compare between the 2 arms. A one-sided significance level of 0.10 will be considered. Will also assess PFS in patients stratified by PD-L1 expression levels in the tumor microenvironment, as assayed by Genentech.
    Duration of response (DOR) [ Time Frame: Up to 2 years ] DOR is measured by RECIST v1.1 and irRECIST. DOR will be summarized using Kaplan-Meier estimates. Long-rank tests will be conducted for OS and PFS to compare between the 2 arms. A one-sided significance level of 0.10 will be considered. Will also assess DOR in patients stratified by PD-L1 expression levels in the tumor microenvironment, as assayed by Genentech.
    Overall survival [ Time Frame: Up to 2 years ] OS will be summarized using Kaplan-Meier estimates. Long-rank tests will be conducted for OS and PFS to compare between the 2 arms. A one-sided significance level of 0.10 will be considered. Will also assess OS in patients stratified by PD-L1 expression levels in the tumor microenvironment, as assayed by Genentech.

    Other Outcome Measures: Assessment of investigation treatment combination on the immune-bias of the tumor microenvironment [ Time Frame: Up to 2 years ] The evaluation of the effect of the investigation treatment combination on the immune-bias of the tumor microenvironment, based upon baseline and post-baseline tumor biopsy comparisons of number, distribution, and phenotype of tumor-infiltrating cells; PD-L1 expression, and expression of Interferon gamma (IFN-gamma) and associated proinflammatory gene expression in the tumor microenvironment.

    TRIAL NUMBER: EA8185

    Title: Phase 2 Study of Bladder-SparIng ChemoradiatioN with MEDI4736 (Durvalumab) in clinical Stage 3, Node PosItive bladdeR cancEr (INSPIRE)

    Purpose:

    Primary Outcome Measures :
    1. Clinical complete response (CR) [ Time Frame: Up to 6 years ]

    Secondary Outcome Measures :
    1. Metastasis-free survival [ Time Frame: From randomization to first evidence of metastatic disease or death from any cause, assessed up to 6 years ]
      Will be estimated by the Kaplan-Meier method.

    2. Bladder-intact event-free survival (BI-EFS) [ Time Frame: From randomization to the first BI-EFS event, assessed up to 6 years ]
      Will be estimated by the Kaplan-Meier method.

    3. Bladder cancer specific survival [ Time Frame: From randomization to death from bladder cancer, assessed up to 6 years ]
      Will be estimated by the Kaplan-Meier method.

    4. Overall survival [ Time Frame: From randomization to death from any cause, assessed up to 6 years ]
      Will be estimated by the Kaplan-Meier method.

    5. Progression-free survival [ Time Frame: From randomization to first of local progression, nodal or distant metastasis, or death from any cause, assessed up to 6 years ]
      Will be estimated by the Kaplan-Meier method.

    6. Complete response duration [ Time Frame: From the date of the biopsy documenting the complete response to the time of muscle invasive recurrence, local progression, evidence of metastatic disease or death due to any cause, assessed up to 6 years ]
      Stratified Cox proportional hazards models will be used to estimate hazard ratios in all eligible patients.

    7. Salvage cystectomy rate [ Time Frame: Up to 6 years ]
      Rate will be reported as a proportion of patients who do not experience clinical benefit after chemoradiotherapy (chemoRT) +/- MEDI4736 (durvalumab) along with a 90% confidence interval. Stratified Cox proportional hazards models will be used to estimate hazard ratios in all eligible patients.

    8. Incidence of adverse events [ Time Frame: Up to 1 year ]
      Assessed using the Common Terminology Criteria for Adverse Events (CTCAE). Toxicity will be evaluated in all treated patients, regardless of eligibility.

    TRIAL NUMBER: S1806

    Title: S1806: Phase III Randomized Trial of Concurrent Chemoradiotherapy with or Without Atezolizumab in Localized Muscle Invasive Bladder Cancer

    Purpose: This phase III trial studies how well chemotherapy and radiation therapy work with or without atezolizumab in treating patients with localized muscle invasive bladder cancer. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as gemcitabine, cisplatin, fluorouracil and mitomycin-C, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with radiation therapy may kill more tumor cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving atezolizumab with radiation therapy and chemotherapy may work better in treating patients with localized muscle invasive bladder cancer compared to radiation therapy and chemotherapy without atezolizumab.

    TRIAL NUMBER: S1418

    Title: A Randomized, Phase III Trial to Evaluate the Efficacy and Safety of MK-3475 (Pembrolizumab) as Adjuvant Therapy for Triple Receptor-Negative Breast Cancer With ? 1 cm Residual Invasive Cancer or Positive Lymph Nodes (ypN+) After Neoadjuvant Chemotherapy

    Purpose: This randomized phase III trial studies how well pembrolizumab works in treating triple-negative breast cancer. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

    TRIAL NUMBER: DCP-001

    Title: DCP-001, Use of a Clinical Trial Screening Tool to Address Cancer Health Disparities in the NCI Community Oncology Research Program (NCORP)

    Purpose: The protocol is not a scientific study; rather, a method to implement the screening tool and allow the collection and analyses of expanded data with informed consent. Investigators also enroll patients into NCI-treatment trials. The tool, based on a screening log successfully used within the NCI Community Cancer Centers Program (NCCCP), has been streamlined and integrated into the sites’ workflow by using OPEN. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. Also missing from the existing data is the context of care, within the communities themselves where most cancer and at risk of cancer patients receive care which is the focus of NCORP. The profile of patients accrued to NCI-sponsored clinical trials lacks both racial/ethnic and socioeconomic diversity. Accrued patients tend to be insured, highly educated and of higher socioeconomic means. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. NCORP's clinical trials portfolio includes cancer control, prevention, screening, symptom science, and cancer care delivery research.

    TRIAL NUMBER: DCP-002

    Title: DCP-002 Early Onset Malignancies Initiative (EOMI): Molecular profiling of Breast, Prostate, Colorectal, Liver, Kidney, and Multiple Myeloma among Racially and Ethnically Diverse Populations

    Purpose: The primary objective of the EOMI (Early Onset Malignancy Initiative) is to acquire tissue and blood, and other biospecimens for research purposes from tests performed for clinical care or for research indications on other research protocols to accelerate our understanding of the molecular basis of early onset cancers occurring in racial and/or ethnic minority populations through the application of genome analysis technologies, including large-scale genome sequencing and clinical data analysis.

    TRIAL NUMBER: EA2165

    Title: Nivolumab After Combined Modality Therapy in Treating Patients With High Risk Stage II-IIIB Anal Cancer

    Purpose: This randomized phase II clinical trial studies how well nivolumab after combined modality therapy works in treating patients with high risk stage II-IIIB anal cancer. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

    TRIAL NUMBER: A031702

    Title: Phase II Study of Cabozantinib in Combination with Nivolumab and Ipilimumab in Rare Genitourinary Tumors

    Purpose: Primary Outcome Measures :
    Objective response rate (ORR) [ Time Frame: Up to 5 years ] An objective response is defined as a confirmed complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. Will be estimated by the number of confirmed objective responses divided by the total number of evaluable patients. Confidence intervals for the true ORR will be calculated.

    Secondary Outcome Measures :
    Duration of response [ Time Frame: From time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years ] Defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented.
    Progression-free survival (PFS) [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 5 years ] The median its 95% confidence interval will be determined and will be summarized using the Kaplan-Meier estimator.
    Overall survival [ Time Frame: Up to 5 years ] The median its 95% confidence interval will be determined and will be summarized using the Kaplan-Meier estimator.
    Clinical benefit rate (CBR) [ Time Frame: Up to 5 years ] A confirmed clinical benefit is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart or a confirmed stable disease at two consecutive tumor assessments at least 3 months apart. The CBR will be estimated by the number of patients with confirmed clinical benefit divided by the total number of evaluable patients. Confidence intervals for the true CBR will be calculated using exact binomial confidence intervals.
    Incidence of adverse events (AE) [ Time Frame: Up to 5 years ] Will be assessed using Common Terminology Criteria for Adverse Events version 5.0. The maximum of a particular AE will be determined for each patient. Tables will summarize the number and relative frequency of patients observing an AE as well as the number and relative frequency of patients experiencing any AE of grade 3 or greater.

    Other Outcome Measures:
    Effects of treatment in patients with bone-only disease [ Time Frame: Up to 5 years ] The bone-only tumor patients will be evaluated in an exploratory fashion (if no RECIST measurements are available). A maximum of 15 patients with bone-only disease will be enrolled and evaluated using PFS for a descriptive analysis of the effect of treatment.

    TRIAL NUMBER: NRG GU005

    Title: Phase III IGRT and SBRT Vs IGRT and Hypofractionated IMRT for Localized Intermediate Risk Prostate Cancer

    Purpose: 1. OBJECTIVES 1.1 Primary Objectives ? To determine whether SBRT can be shown to be superior to hypofractionated IMRT in terms of GU and GI toxicity by having fewer patients that experience a minimal important decline (MID) in urinary irritation/obstructive and bowel HRQOL as measured by EPIC-26 at 24 months post completion of therapy. ? To determine if SBRT (5 fractions of 7.25 Gy) is superior to hypofractionated IMRT (28 fractions of 2.5 Gy) as measured by Disease Free Survival (DFS) 1.2 Secondary Objectives ? Secondary ObjectivesTo determine whether SBRT can be shown to be superior to hypofractionated IMRT at 12 and 24 months post completion of therapy in terms of HRQOL by having fewer patients that experience a minimal important decline (MID) bowel (12 months only) sexual, hormonal, urinary irritation/obstructive (12 months only) and in urinary incontinence HRQOL as measured by EPIC-26 ? To determine if SBRT (5 fractions of 7.25 Gy) is superior to hypofractionated IMRT (28 fractions of 2.5 Gy) as measured by biochemical failure, overall survival, local failure, prostate cancer specific survival, and distant metastases ? To determine the correspondence between the diagnostic MRI and biopsy 1.3 Exploratory Objectives ? To determine whether a potentially more expensive therapy, SBRT, would be cost-effective than standard hypofractionated IMRT as measured by the EQ-5D-5L ? To explore the relationship between PIRADSv2 grade with biochemical failure ? Collect specimens for future translational research analyses

    TRIAL NUMBER: NRG-GY006

    Title: A Randomized Phase II Trial of Radiation Therapy and Cisplatin Alone or in Combination with Intravenous Triapine in Women with Newly Diagnosed Bulky Stage IB2, Stage II, IIIB, or IVA Cancer of the Uterine Cervix or Stage II-IVA Vaginal Cancer

    Purpose: This randomized phase II trial studies radiation therapy and cisplatin with triapine to see how well they work compared to the standard radiation therapy and cisplatin alone in treating patients with newly diagnosed stage IB2, II, or IIIB-IVA cervical cancer or stage II-IVA vaginal cancer. Radiation therapy uses high energy protons to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether radiation therapy and cisplatin are more effective with triapine in treating cervical or vaginal cancer.

    TRIAL NUMBER: NRG-GY020

    Title: A Phase III Randomized Trial of Radiation +/- MK-3475 (Pembrolizumab) for Newly Diagnosed Early Stage High Intermediate Risk Mismatch Repair Deficient (dMMR) Endometrioid Endometrial Cancer

    Purpose: This phase III trial compares whether the addition of pembrolizumab to radiation therapy is more effective than radiation therapy alone in reducing the risk of cancer coming back (recurrence) in patients with newly diagnosed stage I-II endometrial cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. The addition of pembrolizumab to radiation treatment may be more effective than radiation treatment alone in reducing cancer recurrence.

    TRIAL NUMBER: NRG-HN004

    Title: Randomized Phase II/III Trial of Radiotherapy with Concurrent MEDI4736 (Durvalumab) vs. Radiotherapy with Concurrent Cetuximab in Patients with Stage III-IVB Head and Neck Cancer with a Contraindication to Cisplatin

    Purpose: PRIMARY OBJECTIVES:
    I. To determine whether radiotherapy (RT) with concurrent and adjuvant anti-PD-L1 therapy (durvalumab) is feasible in patients with locoregionally advanced head and neck cancer (HNC) who have a contraindication to cisplatin. (Lead-in) II. To test the hypothesis that concurrent RT and anti-PD-L1 therapy improves progression free survival (PFS) compared to standard therapy (RT with concurrent cetuximab) in patients with locoregionally advanced HNC who have a contraindication to cisplatin. (Phase II) III. To test the hypothesis that concurrent RT and anti-PD-L1 therapy improves overall survival compared to standard therapy (RT with concurrent cetuximab) in patients with locoregionally advanced HNC who have a contraindication to cisplatin. (Phase III)
    SECONDARY OBJECTIVES:
    I. To compare toxicity between patients treated with RT + anti-PD-L1 therapy versus RT/cetuximab.
    II. To test the effect of anti-PD-L1 therapy in the subpopulation of patients with tumors that overexpress PD-L1.
    III. To compare overall survival, response (at 4-month fludeoxyglucose F-18 [FDG]-positron emission tomography [PET]-computed tomography [CT]), locoregional failure, distant metastasis, and competing mortality in the two arms by known risk factors, including p16 status and omega score.
    IV. To test the hypothesis that durvalumab therapy arm will improved 1 year quality of life (QOL) compared to the cetuximab arm using European Organization for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-core [C]30 version 3.0) / Head-and-Neck module (EORTC QLQ/H&N35) and other quality of life (QOL) tools.
    TERTIARY OBJECTIVES:
    I. To test the hypothesis that radiation combined with durvalumab enhances the adaptive immune response using three types of immunophenotyping compared to radiation combined with cetuximab.
    OUTLINE: Patients are randomized to 1 of 2 arms.
    ARM I: Patients receive cetuximab intravenously (IV) over 120 minutes weekly. Treatment repeats every week for up to 8 courses in the absence of disease progression or unacceptable toxicity. Beginning 5-7 days after first cetuximab dose, patients undergo intensity modulated radiation therapy (IMRT) 5 fractions per week for up to 7 weeks.
    ARM II: Patients receive durvalumab IV over 60 minutes every 4 weeks. Treatment repeats every 4 weeks for up to 7 courses in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients undergo IMRT 5 fractions per week for up to 7 weeks.
    After completion of study treatment, patients are followed up at 1 month, every 4 months for 1 year, every 6 months for 2 years, then annually thereafter.

    TRIAL NUMBER: A031704

    Title: PD-Inhibitor (Nivolumab) and Ipilimumab Followed by Nivolumab Vs. VEGF TKI Cabozantinib with Nivolumab: A Phase III Trial in Metastatic Untreated REnal Cell CancEr [PDIGREE]

    Purpose: This phase III trial studies how well nivolumab and ipilimumab, followed by nivolumab versus cabozantinib and nivolumab, work in treating patients with renal cell cancer that is untreated and has spread to other parts of the body. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cabozantinib, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known how well cabozantinib and nivolumab work in treating patients with untreated renal cell cancer that has spread to other parts of the body.

    TRIAL NUMBER: EA8143

    Title: EA8143:A Phase 3 RandOmized Study Comparing PERioperative Nivolumab vs. Observation in Patients with Localized Renal Cell Carcinoma Undergoing Nephrectomy (PROSPER RCC)

    Purpose: The purpose of this study is to compare any good and bad effects of using nivolumab (also known as OPDIVO®), before and after the kidney cancer surgery to using the usual approach of surgically removing the kidney cancer followed by standard post-operative follow-up and monitoring. Nivolumab is a drug that may help stimulate your immune system to attack any cancer cells that may remain after surgery. The addition of nivolumab to the usual surgery could prevent your cancer from returning but it could also cause side effects. This research study will allow researchers to find out whether this different treatment is better, the same, or worse than the usual treatment for kidney cancer that has been removed but is at risk for coming back The study drug, nivolumab, is already FDA-approved for patients who have kidney cancer that has spread outside of the kidney to other organs or lymph nodes. The use of nivolumab in this study is investigational (not approved by the FDA) for your early stage of cancer where we do not know for sure if the disease has spread outside of the kidney. This research study will allow the researchers to know whether this different approach is better, the same, or worse than the usual approach. To be better, the study drug should improve how long you are able to live without any signs or symptoms of your cancer compared to the usual approach

    TRIAL NUMBER: A151216

    Title: Genetic Testing For Patients with Resectable or Resected Lung Cancer: Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST)

    Purpose: PRIMARY OBJECTIVES:
    I. To centrally genotype resected lung adenocarcinomas for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements to facilitate accrual to randomized adjuvant studies.
    II. To obtain clinically annotated tumor tissue and patient-matched non-malignant deoxyribonucleic acid (DNA) from peripheral blood, as well as detailed epidemiologic and clinical follow-up data, to allow clinically annotated advanced genomic analyses in concert with the National Cancer Institute (NCI) Center for Cancer Genomics (CCG).
    SECONDARY OBJECTIVES:
    I. To characterize the natural history of EGFR and ALK wild-type lung cancers to allow subsequent development of targeted therapies against genotype-defined sub-populations in the adjuvant and recurrent settings.
    II. To cross-validate local genotyping assays for EGFR and ALK with a central reference standard.
    TERTIARY OBJECTIVES:
    I. To study the genomic evolution of lung cancers by comparing genomic characteristics at resection and at recurrence.
    OUTLINE:
    Patients undergo collection of blood and tissue samples for EGFR and ALK testing via direct sequencing and fluorescence in situ hybridization (FISH). Patients that have had surgery prior to pre-registration will submit samples from the previous surgery for testing.
    After completion of study, patients that are not enrolled on either A081105 or E4512 are followed up every 6 months for 5 years.

    TRIAL NUMBER: E4512

    Title: A Phase III Double-Blind Trial for Surgically Resected Early Stage Non-Small Cell Lung Cancer: Crizotinib versus Placebo for Patients with Tumors Harboring the Anaplastic Lymphoma Kinase (ALK) Fusion Protein

    Purpose: PRIMARY OBJECTIVES:
    I. To evaluate whether adjuvant therapy with crizotinib will result in improved overall survival (OS) over placebo for patients with stage IB >= 4 cm, II and IIIA, anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) following surgical resection.
    SECONDARY OBJECTIVES:
    I. To evaluate and compare disease-free survival (DFS) associated with crizotinib and placebo.
    II. To evaluate the safety profile of crizotinib when given in the adjuvant therapy setting.
    III. To collect tumor tissue and blood specimens for future research.
    OUTLINE: Patients are randomized to 1 of 2 treatment arms.
    ARM A: Patients receive crizotinib orally (PO) twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
    ARM B: Patients receive placebo PO BID on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
    After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly for 5 years.

    TRIAL NUMBER: S1827

    Title: A RANDOMIZED PHASE III TRIAL OF MRI SURVEILLANCE WITH OR WITHOUT PROPHYLACTIC CRANIAL IRRADIATION (PCI) IN SMALL-CELL LUNG CANCER

    Purpose:

    Primary Outcome Measures :
    1. Overall survival (OS) [ Time Frame: From the date of registration to date of death due to any cause, assessed up to 2 years after randomization ]
      Will evaluate OS with magnetic resonance imaging (MRI) surveillance alone and MRI surveillance combined with prophylactic cranial irradiation (PCI) for the treatment of small cell lung cancer (SCLC).


    Secondary Outcome Measures :
    1. Cognitive failure-free survival (CFFS) [ Time Frame: Baseline to first neurocognitive failure CF or death due to any cause, assessed up to 12 months after randomization ]
      The comparison of CFFS up to 12 months between the arms will be done using a 1-sided 5% level log-rank test.

    2. CFFS rate [ Time Frame: Baseline to first neurocognitive failure CF or death due to any cause, assessed at 90, 180, 270, 360, 540, and 720 days after randomization ]
      There will be a comparison of the CFFS rates between the arms at each of the assessment times and the cumulative incidence of cognitive failure, evaluating death as a competing risk. The CFFS rates at the landmark times will be estimated using the method of Kaplan-Meier and the difference in rates will be evaluated using a 90% confidence interval using Greenwood?s formula.

    3. Cumulative incidence of cognitive failure [ Time Frame: Neurocognitive function test will be assessed at 90, 180, 270, 360, 540, and 720 days after randomization ]
      The cumulative incidence of cognitive failure in the presence of the competing risk of death will be estimated used the method of Fine and Gray.

    4. OS in an "as-treated" analysis [ Time Frame: From the date of registration to date of death due to any cause, assessed up to 2 years after randomization. Patients will be seen at day 90, 180, 270, 360, 540, and 720 ]
      The comparison of OS in the ?as-treated? analysis will be done as described for the primary analysis, however patients will be categorized per treatment received (patients who do not accept their randomized assignment will be analyzed per treatment received). The number of patients not accepting the randomized assignment will also be summarized.

    5. Brain metastases-free survival (BMFS) [ Time Frame: Up to 2 years after randomization. Patients will have MRI on day 90, 180, 270, 360, 540, and 720 ]
      This will be estimated using the method of Kaplan-Meier and comparisons will be done using a log-rank test at the 1-sided 0.05 level. Hazard ratios and associated confidence intervals will be estimated using a Cox Proportional hazards model. Confidence intervals for medians will be estimated using the method of Brookmeyer-Crowley.

    6. Incidence of adverse events [ Time Frame: Up to 2 years after randomization. Patients will be assessed for adverse event after PCI (for patients on PCI + MRI arm) and at month 3 (all patients) ]
      Binary proportions and associated confidence intervals will be estimated.

    TRIAL NUMBER: 10231

    Title: NCORP TISSUE PROCUREMENT PROTOCOL: AN NCI CANCER MOONSHOT(SM) STUDY

    Purpose: Primary Outcome Measures : Obtaining tumor tissue and blood specimens [ Time Frame: Up to 2 years ] Will obtain tumor tissue and blood specimens for biobanking and to store tissues, blood, and nucleic acids for future research, including the study of matched pre and post-treatment tumor biopsies to elucidate mechanisms of resistance. Cases will be grouped according to histology and/or treatment. Secondary Outcome Measures : Tumor tissues storage in the Biopathology Center (BPC) at Nationwide Children?s Hospital (NCH) (Biorepository) [ Time Frame: Up to 2 years ] Genomic analysis [ Time Frame: Up to 2 years ] Will perform genomic studies, including a pan-cancer gene panel, and contribute molecular data to the genomic data commons. Biospecimen Retention: Samples With DNA Blood, tissue

    TRIAL NUMBER: EAY131

    Title: EAY131: Molecular Analysis for Therapy Choice (NCI-MATCH)

    Purpose: This phase II trial studies how well treatment that is directed by genetic testing works in patients with solid tumors or lymphomas that have progressed following at least one line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment which targets their tumor's particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors or lymphomas.

    TRIAL NUMBER: NCICOVID

    Title: NCI COVID-19 in Cancer Patients Study (NCCAPS): A Longitudinal Natural History Study

    Purpose: This study collects blood samples, medical information, and medical images from patients who are being treated for cancer and have a positive test for SARS CoV-2, the new coronavirus that causes the disease called COVID-19. Collecting blood samples, medical information, and medical images may help researchers determine how COVID-19 affects the outcomes of patients undergoing cancer treatment and how having cancer affects COVID-19.

    TRIAL NUMBER: S1609

    Title: SWOG 1609: DART: Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors Treatment with Ipilimumab and Nivolumab for Rare Cancers

    Purpose: Both Ipilimumab and Nivolumab have already been FDA-approved to treat other cancers. However, Ipilimumab and Nivolumab are investigational and not FDA-approved for use in combination in treating rare cancers or cancers of unknown primary origin.

    TRIAL NUMBER: EA8171

    Title: EA8171:Multiparametric MRI (mpMRI) for Preoperative Staging and Treatment Planning for Newly-Diagnosed Prostate Cancer

    Purpose: This phase II trial studies how well multiparametric magnetic resonance imaging (MRI) works in evaluating cancer stage and helping treatment planning in patients with prostate cancer. Multiparametric MRI may be useful for evaluating the type of cancer in finding aggressive disease.

    TRIAL NUMBER: NRG-GU002

    Title: NRG-GU002: PHASE II-III TRIAL OF ADJUVANT RADIOTHERAPY AND ANDROGEN DEPRIVATION FOLLOWING RADICAL PROSTATECTOMY WITH OR WITHOUT ADJUVANT DOCETAXEL

    Purpose: This randomized phase II/III trial studies docetaxel, antiandrogen therapy, and radiation therapy to see how well it works compared with antiandrogen therapy and radiation therapy alone in treating patients with prostate cancer that has been removed by surgery. Androgen can cause the growth of prostate cells. Antihormone therapy may lessen the amount of androgen made by the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving antiandrogen therapy and radiation therapy with or without docetaxel after surgery may kill any remaining tumor cells.

    TRIAL NUMBER: S1802

    Title: S1802: Phase III Randomized Trial of Standard Systemic Therapy (SST) versus Standard Systemic Therapy plus Definitive treatment (surgery or radiation) of the primary tumor in Metastatic Prostate Cancer

    Purpose: This phase III trial studies how well standard systemic therapy with or without definitive treatment (prostate removal surgery or radiation therapy) works in treating participants with prostate cancer that has spread to other places in the body. Addition of prostate removal surgery or radiation therapy to standard systemic therapy for prostate cancer may lower the chance of the cancer growing or spreading.

    TRIAL NUMBER: A031801

    Title: A PHASE II RANDOMIZED TRIAL OF RADIUM-223 DICHLORIDE AND CABOZANTINIB IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA WITH BONE METASTASIS (RADICAL)

    Purpose:

    Primary Outcome Measures :
    1. Symptomatic skeletal event (SSE)-free survival (FS) [ Time Frame: From the date of randomization to the date of the earliest occurrence of SSE or death from any cause, assessed up to 5 years ]
      SSE-FS distribution will be estimated using the method of Kaplan-Meier by treatment arm. Comparison between the two arms will be performed using a one-sided log-rank test and one-sided p-value less than 0.025 will indicate that the experimental arm is superior to the control arm. SSE-FS will be censored at the date of last SSE assessment for those alive and SSE free. Hazard ratio (experimental over control arm) as well as two-sided 90% confidence interval (CI) for treatment will be estimated using the stratified Cox proportional hazard model with a single treatment covariate.


    Secondary Outcome Measures :
    1. Incidence of adverse events [ Time Frame: Up to 5 years ]
      Will be determined using Common Terminology Criteria for Adverse Events version 5.0. Adverse events will be summarized and compared between arms using chi-square or fisher exact tests as appropriate.

    2. SSE-FS [ Time Frame: From randomization to the date of SSE or death due to any cause, whichever comes first, assessed up to 5 years ]
      Will be estimated with the Kaplan Meier methodology. Comparison between arms or between predefined groups will be conducted using the log-rank test.

    3. Progression-free survival [ Time Frame: From randomization to time of radiographic progression or death due to any cause, whichever occurs first, assessed up to 5 years ]
      Radiographic progression will be defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Will be estimated with the Kaplan Meier methodology. Comparison between arms or between predefined groups will be conducted using the log-rank test.

    4. Overall survival [ Time Frame: From randomization to the date of death due to any cause, assessed up to 5 years ]
      Will be estimated with the Kaplan Meier methodology. Comparison between arms or between predefined groups will be conducted using the log-rank test. Patients who are alive will be censored at last follow up date.

    5. Time to first SSE [ Time Frame: From randomization to the date of first SSE or death due to any cause, assessed up to 5 years ]
      Will be determined in each treatment. The median estimate to first SSE-FS will be calculated.

    6. Overall response rate (ORR) [ Time Frame: Up to 5 years ]
      Will be defined by RECIST version 1.1. Number and proportion of patients achieving ORR (by RECIST) will be summarized with two-sided 90% CI by treatment arm; comparison between arms will be conducted using chi-square or Fisher's exact test as appropriate.

    TRIAL NUMBER: A031501

    Title: PHASE III RANDOMIZED ADJUVANT STUDY OF MK-3475 (PEMBROLIZUMAB) IN MUSCLE INVASIVE AND LOCALLY ADVANCED UROTHELIAL CARCINOMA (AMBASSADOR) VERSUS OBSERVATION

    Purpose: Primary Outcome Measures: Disease-free survival [ Time Frame: From randomization to the first metastatic recurrence (presence of any recurrent disease), or death, whichever occurs first, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.
    Overall survival [ Time Frame: From randomization to the date of death from any cause, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.

    Secondary Outcome Measures: Disease-free survival in PD-L1 positive and negative patients [ Time Frame: From randomization to the first metastatic recurrence (presence of any recurrent disease), or death, whichever occurs first, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.
    Overall survival in PD-L1 positive and negative patients [ Time Frame: From randomization to the date of death from any cause, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.

    Estimated Enrollment: 739 Actual Study Start Date: September 21, 2017 Estimated Study Completion Date: February 28, 2019 Estimated Primary Completion Date: February 28, 2019 (Final data collection date for primary outcome measure)

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    TRIAL NUMBER: A031803

    Title: PHASE II TRIAL OF INTRAVESICAL GEMCITABINE AND MK-3475 (PEMBROLIZUMAB) IN THE TREATMENT OF PATIENTS WITH BCG- NRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER

    Purpose:

    Primary Outcome Measures :
    1. Complete response rate in the carcinoma in situ (CIS) subpopulation [ Time Frame: At 6 months ]
      A complete response, only for patients with a CIS component, is a cystoscopy without evidence of bladder tumor, negative biopsy (including directed biopsies to any suspicious areas and in addition random bladder biopsies including trigone, left lateral wall, right lateral wall, posterior bladder, dome of bladder, and the prostatic urethra in men) and negative cytology for high grade disease at 6 months (end of cycle 8, week 25).

    2. Event-free survival at 18 months [ Time Frame: From the date of study registration to the first documentation of an event or death whichever comes first, assessed up to 18 months ]
      EFS will be measure from the date of study registration to the first documentation of an event or death whichever comes first. For patients without a documented event and who are still alive, they will be censored at last disease assessment. For patients who start any subsequent ant-cancer therapy without any reported events will be censored at their last disease assessment. will be obtained with a Kaplan-Meier estimator (using the Greenwood formula to estimate the variance) for the entire 155 patient group consisting of patients with CIS, CIS with Ta/T1 or Ta or T1 disease. A 90% confidence interval will be generated for the 18-month EFS estimate.


    Secondary Outcome Measures :
    1. Incidence of adverse events [ Time Frame: Up to 5 years post treatment ]
      Adverse events will be assessed based on the National Cancer Institute (NCI) common toxicity criteria (Common Terminology Criteria for Adverse Events [CTACAE] version [v] 5.0).

    2. Duration of response (DOR) [ Time Frame: From the time a patient had a documented response that had been confirmed (the time would start at the time a response was first noted) until disease-progression, assessed up to 5 years ]
      Analysis will only include those patients with a confirmed response. Patients who are alive and without a documented progression at the time of analysis will be censored at the time of the last disease status evaluation. The Kaplan-Meier product-limit estimator will be used to estimate DOR, medians and 95% confidence intervals (CI).

    3. Progression-free survival (PFS) [ Time Frame: From the date of study registration to the date of progression or death due to any cause, whichever occurs first, assessed up to 5 years ]
      Surviving patients without any documented progressions will be censored at the date of last known contact. Progression will be defined as the development of muscle invasive bladder cancer or metastatic urothelial cancer (nodal and/or distant). The Kaplan-Meier product-limit estimator will be used to estimate PFS, medians and 95% CI.

    4. Overall survival (OS) [ Time Frame: From the date of study registration to date of death due to any cause, assessed up to 5 years ]
      Surviving patients will be censored at the date of last known contact. The Kaplan-Meier product-limit estimator will be used to estimate OS, medians and 95% CI.

    5. Cystectomy-free survival [ Time Frame: From the date of study registration to the date of cystectomy for all patients ]
      The Kaplan-Meier product-limit estimator will be used to estimate cystectomy-free survival, medians and 95% CI.

    6. Recurrence free survival (RFS) [ Time Frame: From the date of study registration to the first documentation of recurrence or death due to any cause, assessed up to 5 years ]
      Surviving patients without any documented recurrence will be censored at the date of last known contact. Recurrence will be defined as the development of high-grade bladder cancer for patients with a CIS component only and those without a CIS component. The Kaplan-Meier product-limit estimator will be used to estimate RFS, medians and 95% CI.

    TRIAL NUMBER: EA8185

    Title: Phase 2 Study of Bladder-SparIng ChemoradiatioN with MEDI4736 (Durvalumab) in clinical Stage 3, Node PosItive bladdeR cancEr (INSPIRE)

    Purpose:

    Primary Outcome Measures :
    1. Clinical complete response (CR) [ Time Frame: Up to 6 years ]

    Secondary Outcome Measures :
    1. Metastasis-free survival [ Time Frame: From randomization to first evidence of metastatic disease or death from any cause, assessed up to 6 years ]
      Will be estimated by the Kaplan-Meier method.

    2. Bladder-intact event-free survival (BI-EFS) [ Time Frame: From randomization to the first BI-EFS event, assessed up to 6 years ]
      Will be estimated by the Kaplan-Meier method.

    3. Bladder cancer specific survival [ Time Frame: From randomization to death from bladder cancer, assessed up to 6 years ]
      Will be estimated by the Kaplan-Meier method.

    4. Overall survival [ Time Frame: From randomization to death from any cause, assessed up to 6 years ]
      Will be estimated by the Kaplan-Meier method.

    5. Progression-free survival [ Time Frame: From randomization to first of local progression, nodal or distant metastasis, or death from any cause, assessed up to 6 years ]
      Will be estimated by the Kaplan-Meier method.

    6. Complete response duration [ Time Frame: From the date of the biopsy documenting the complete response to the time of muscle invasive recurrence, local progression, evidence of metastatic disease or death due to any cause, assessed up to 6 years ]
      Stratified Cox proportional hazards models will be used to estimate hazard ratios in all eligible patients.

    7. Salvage cystectomy rate [ Time Frame: Up to 6 years ]
      Rate will be reported as a proportion of patients who do not experience clinical benefit after chemoradiotherapy (chemoRT) +/- MEDI4736 (durvalumab) along with a 90% confidence interval. Stratified Cox proportional hazards models will be used to estimate hazard ratios in all eligible patients.

    8. Incidence of adverse events [ Time Frame: Up to 1 year ]
      Assessed using the Common Terminology Criteria for Adverse Events (CTCAE). Toxicity will be evaluated in all treated patients, regardless of eligibility.

    TRIAL NUMBER: S1600

    Title: A Randomized Phase III Double-Blind Clinical Trial Evaluating the Effect of Immune-Enhancing Nutrition on Radical Cystectomy Outcomes

    Purpose: This randomized phase III trial studies how well nutrition therapy works in improving immune system in patients with bladder cancer that can be removed by surgery. Improving nutrition before and after surgery may reduce the infections and other problems that sometimes occur after surgery.

    TRIAL NUMBER: S1806

    Title: S1806: Phase III Randomized Trial of Concurrent Chemoradiotherapy with or Without Atezolizumab in Localized Muscle Invasive Bladder Cancer

    Purpose: This phase III trial studies how well chemotherapy and radiation therapy work with or without atezolizumab in treating patients with localized muscle invasive bladder cancer. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as gemcitabine, cisplatin, fluorouracil and mitomycin-C, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with radiation therapy may kill more tumor cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving atezolizumab with radiation therapy and chemotherapy may work better in treating patients with localized muscle invasive bladder cancer compared to radiation therapy and chemotherapy without atezolizumab.

    TRIAL NUMBER: DCP-001

    Title: DCP-001, Use of a Clinical Trial Screening Tool to Address Cancer Health Disparities in the NCI Community Oncology Research Program (NCORP)

    Purpose: The protocol is not a scientific study; rather, a method to implement the screening tool and allow the collection and analyses of expanded data with informed consent. Investigators also enroll patients into NCI-treatment trials. The tool, based on a screening log successfully used within the NCI Community Cancer Centers Program (NCCCP), has been streamlined and integrated into the sites’ workflow by using OPEN. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. Also missing from the existing data is the context of care, within the communities themselves where most cancer and at risk of cancer patients receive care which is the focus of NCORP. The profile of patients accrued to NCI-sponsored clinical trials lacks both racial/ethnic and socioeconomic diversity. Accrued patients tend to be insured, highly educated and of higher socioeconomic means. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. NCORP's clinical trials portfolio includes cancer control, prevention, screening, symptom science, and cancer care delivery research.

    TRIAL NUMBER: DCP-002

    Title: DCP-002 Early Onset Malignancies Initiative (EOMI): Molecular profiling of Breast, Prostate, Colorectal, Liver, Kidney, and Multiple Myeloma among Racially and Ethnically Diverse Populations

    Purpose: The primary objective of the EOMI (Early Onset Malignancy Initiative) is to acquire tissue and blood, and other biospecimens for research purposes from tests performed for clinical care or for research indications on other research protocols to accelerate our understanding of the molecular basis of early onset cancers occurring in racial and/or ethnic minority populations through the application of genome analysis technologies, including large-scale genome sequencing and clinical data analysis.

    TRIAL NUMBER: S1823

    Title: A PROSPECTIVE OBSERVATIONAL COHORT STUDY TO ASSESS miRNA 371 FOR OUTCOME PREDICTION IN PATIENTS WITH NEWLY DIAGNOSED GERM CELL TUMORS

    Purpose:

    Primary Outcome Measures :
    1. Relapse rate of active germ cell malignancy for those undergoing active surveillance of clinical stage I (CSI)/stage IIA germ cell malignancy [ Time Frame: Up to 3 years ]
    2. Positive predictive value [ Time Frame: Up to 3 years ]

    Biospecimen Retention:   Samples With DNA
    Blood

    TRIAL NUMBER: A031702

    Title: Phase II Study of Cabozantinib in Combination with Nivolumab and Ipilimumab in Rare Genitourinary Tumors

    Purpose: Primary Outcome Measures :
    Objective response rate (ORR) [ Time Frame: Up to 5 years ] An objective response is defined as a confirmed complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. Will be estimated by the number of confirmed objective responses divided by the total number of evaluable patients. Confidence intervals for the true ORR will be calculated.

    Secondary Outcome Measures :
    Duration of response [ Time Frame: From time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years ] Defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented.
    Progression-free survival (PFS) [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 5 years ] The median its 95% confidence interval will be determined and will be summarized using the Kaplan-Meier estimator.
    Overall survival [ Time Frame: Up to 5 years ] The median its 95% confidence interval will be determined and will be summarized using the Kaplan-Meier estimator.
    Clinical benefit rate (CBR) [ Time Frame: Up to 5 years ] A confirmed clinical benefit is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart or a confirmed stable disease at two consecutive tumor assessments at least 3 months apart. The CBR will be estimated by the number of patients with confirmed clinical benefit divided by the total number of evaluable patients. Confidence intervals for the true CBR will be calculated using exact binomial confidence intervals.
    Incidence of adverse events (AE) [ Time Frame: Up to 5 years ] Will be assessed using Common Terminology Criteria for Adverse Events version 5.0. The maximum of a particular AE will be determined for each patient. Tables will summarize the number and relative frequency of patients observing an AE as well as the number and relative frequency of patients experiencing any AE of grade 3 or greater.

    Other Outcome Measures:
    Effects of treatment in patients with bone-only disease [ Time Frame: Up to 5 years ] The bone-only tumor patients will be evaluated in an exploratory fashion (if no RECIST measurements are available). A maximum of 15 patients with bone-only disease will be enrolled and evaluated using PFS for a descriptive analysis of the effect of treatment.

    TRIAL NUMBER: NRG GU005

    Title: Phase III IGRT and SBRT Vs IGRT and Hypofractionated IMRT for Localized Intermediate Risk Prostate Cancer

    Purpose: 1. OBJECTIVES 1.1 Primary Objectives ? To determine whether SBRT can be shown to be superior to hypofractionated IMRT in terms of GU and GI toxicity by having fewer patients that experience a minimal important decline (MID) in urinary irritation/obstructive and bowel HRQOL as measured by EPIC-26 at 24 months post completion of therapy. ? To determine if SBRT (5 fractions of 7.25 Gy) is superior to hypofractionated IMRT (28 fractions of 2.5 Gy) as measured by Disease Free Survival (DFS) 1.2 Secondary Objectives ? Secondary ObjectivesTo determine whether SBRT can be shown to be superior to hypofractionated IMRT at 12 and 24 months post completion of therapy in terms of HRQOL by having fewer patients that experience a minimal important decline (MID) bowel (12 months only) sexual, hormonal, urinary irritation/obstructive (12 months only) and in urinary incontinence HRQOL as measured by EPIC-26 ? To determine if SBRT (5 fractions of 7.25 Gy) is superior to hypofractionated IMRT (28 fractions of 2.5 Gy) as measured by biochemical failure, overall survival, local failure, prostate cancer specific survival, and distant metastases ? To determine the correspondence between the diagnostic MRI and biopsy 1.3 Exploratory Objectives ? To determine whether a potentially more expensive therapy, SBRT, would be cost-effective than standard hypofractionated IMRT as measured by the EQ-5D-5L ? To explore the relationship between PIRADSv2 grade with biochemical failure ? Collect specimens for future translational research analyses

    TRIAL NUMBER: WF-1802

    Title: Influence of Primary Treatment for Prostate Cancer on Work Experience (PCW)

    Purpose: The objective of this study is to examine how adenocarcinoma of the prostate treatment differentially affects African American men's ability to work and to describe and compare changes in work ability (as measured through self-reported global work ability item) reported by African American and white adenocarcinoma of the prostate survivors before treatment and 6 months after treatment completion.

    TRIAL NUMBER: A031704

    Title: PD-Inhibitor (Nivolumab) and Ipilimumab Followed by Nivolumab Vs. VEGF TKI Cabozantinib with Nivolumab: A Phase III Trial in Metastatic Untreated REnal Cell CancEr [PDIGREE]

    Purpose: This phase III trial studies how well nivolumab and ipilimumab, followed by nivolumab versus cabozantinib and nivolumab, work in treating patients with renal cell cancer that is untreated and has spread to other parts of the body. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cabozantinib, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known how well cabozantinib and nivolumab work in treating patients with untreated renal cell cancer that has spread to other parts of the body.

    TRIAL NUMBER: EA8143

    Title: EA8143:A Phase 3 RandOmized Study Comparing PERioperative Nivolumab vs. Observation in Patients with Localized Renal Cell Carcinoma Undergoing Nephrectomy (PROSPER RCC)

    Purpose: The purpose of this study is to compare any good and bad effects of using nivolumab (also known as OPDIVO®), before and after the kidney cancer surgery to using the usual approach of surgically removing the kidney cancer followed by standard post-operative follow-up and monitoring. Nivolumab is a drug that may help stimulate your immune system to attack any cancer cells that may remain after surgery. The addition of nivolumab to the usual surgery could prevent your cancer from returning but it could also cause side effects. This research study will allow researchers to find out whether this different treatment is better, the same, or worse than the usual treatment for kidney cancer that has been removed but is at risk for coming back The study drug, nivolumab, is already FDA-approved for patients who have kidney cancer that has spread outside of the kidney to other organs or lymph nodes. The use of nivolumab in this study is investigational (not approved by the FDA) for your early stage of cancer where we do not know for sure if the disease has spread outside of the kidney. This research study will allow the researchers to know whether this different approach is better, the same, or worse than the usual approach. To be better, the study drug should improve how long you are able to live without any signs or symptoms of your cancer compared to the usual approach

    TRIAL NUMBER: A231601CD

    Title: A231601CD: Improving Surgical Care and Outcomes in Older Cancer Patients Through Implementation of an Efficient Pre-Surgical Toolkit (OPTI-Surg)

    Purpose: This trial studies how well the use of a pre-surgical toolkit (OPTI-Surg) works in improving surgical care and outcomes in older participants with cancer. In many elderly patients, surgery can greatly affect physical condition and the ability to return to pre-surgery levels of physical functioning. Providing pre-surgical recommendations may help improve participants' recovery rate and functioning after surgery.

    TRIAL NUMBER: NCICOVID

    Title: NCI COVID-19 in Cancer Patients Study (NCCAPS): A Longitudinal Natural History Study

    Purpose: This study collects blood samples, medical information, and medical images from patients who are being treated for cancer and have a positive test for SARS CoV-2, the new coronavirus that causes the disease called COVID-19. Collecting blood samples, medical information, and medical images may help researchers determine how COVID-19 affects the outcomes of patients undergoing cancer treatment and how having cancer affects COVID-19.

    TRIAL NUMBER: S1609

    Title: SWOG 1609: DART: Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors Treatment with Ipilimumab and Nivolumab for Rare Cancers

    Purpose: Both Ipilimumab and Nivolumab have already been FDA-approved to treat other cancers. However, Ipilimumab and Nivolumab are investigational and not FDA-approved for use in combination in treating rare cancers or cancers of unknown primary origin.

    TRIAL NUMBER: EA8171

    Title: EA8171:Multiparametric MRI (mpMRI) for Preoperative Staging and Treatment Planning for Newly-Diagnosed Prostate Cancer

    Purpose: This phase II trial studies how well multiparametric magnetic resonance imaging (MRI) works in evaluating cancer stage and helping treatment planning in patients with prostate cancer. Multiparametric MRI may be useful for evaluating the type of cancer in finding aggressive disease.

    TRIAL NUMBER: NRG-GU002

    Title: NRG-GU002: PHASE II-III TRIAL OF ADJUVANT RADIOTHERAPY AND ANDROGEN DEPRIVATION FOLLOWING RADICAL PROSTATECTOMY WITH OR WITHOUT ADJUVANT DOCETAXEL

    Purpose: This randomized phase II/III trial studies docetaxel, antiandrogen therapy, and radiation therapy to see how well it works compared with antiandrogen therapy and radiation therapy alone in treating patients with prostate cancer that has been removed by surgery. Androgen can cause the growth of prostate cells. Antihormone therapy may lessen the amount of androgen made by the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving antiandrogen therapy and radiation therapy with or without docetaxel after surgery may kill any remaining tumor cells.

    TRIAL NUMBER: NRG-GU008

    Title: RANDOMIZED PHASE III TRIAL INCORPORATING ABIRATERONE ACETATE WITH PREDNISONE AND APALUTAMIDE AND ADVANCED IMAGING INTO SALVAGE TREATMENT FOR PATIENTS WITH NODE-POSITIVE PROSTATE CANCER AFTER RADICAL PROSTATECTOMY

    Purpose:

    TRIAL NUMBER: S1802

    Title: S1802: Phase III Randomized Trial of Standard Systemic Therapy (SST) versus Standard Systemic Therapy plus Definitive treatment (surgery or radiation) of the primary tumor in Metastatic Prostate Cancer

    Purpose: This phase III trial studies how well standard systemic therapy with or without definitive treatment (prostate removal surgery or radiation therapy) works in treating participants with prostate cancer that has spread to other places in the body. Addition of prostate removal surgery or radiation therapy to standard systemic therapy for prostate cancer may lower the chance of the cancer growing or spreading.

    TRIAL NUMBER: A031801

    Title: A PHASE II RANDOMIZED TRIAL OF RADIUM-223 DICHLORIDE AND CABOZANTINIB IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA WITH BONE METASTASIS (RADICAL)

    Purpose:

    Primary Outcome Measures :
    1. Symptomatic skeletal event (SSE)-free survival (FS) [ Time Frame: From the date of randomization to the date of the earliest occurrence of SSE or death from any cause, assessed up to 5 years ]
      SSE-FS distribution will be estimated using the method of Kaplan-Meier by treatment arm. Comparison between the two arms will be performed using a one-sided log-rank test and one-sided p-value less than 0.025 will indicate that the experimental arm is superior to the control arm. SSE-FS will be censored at the date of last SSE assessment for those alive and SSE free. Hazard ratio (experimental over control arm) as well as two-sided 90% confidence interval (CI) for treatment will be estimated using the stratified Cox proportional hazard model with a single treatment covariate.


    Secondary Outcome Measures :
    1. Incidence of adverse events [ Time Frame: Up to 5 years ]
      Will be determined using Common Terminology Criteria for Adverse Events version 5.0. Adverse events will be summarized and compared between arms using chi-square or fisher exact tests as appropriate.

    2. SSE-FS [ Time Frame: From randomization to the date of SSE or death due to any cause, whichever comes first, assessed up to 5 years ]
      Will be estimated with the Kaplan Meier methodology. Comparison between arms or between predefined groups will be conducted using the log-rank test.

    3. Progression-free survival [ Time Frame: From randomization to time of radiographic progression or death due to any cause, whichever occurs first, assessed up to 5 years ]
      Radiographic progression will be defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Will be estimated with the Kaplan Meier methodology. Comparison between arms or between predefined groups will be conducted using the log-rank test.

    4. Overall survival [ Time Frame: From randomization to the date of death due to any cause, assessed up to 5 years ]
      Will be estimated with the Kaplan Meier methodology. Comparison between arms or between predefined groups will be conducted using the log-rank test. Patients who are alive will be censored at last follow up date.

    5. Time to first SSE [ Time Frame: From randomization to the date of first SSE or death due to any cause, assessed up to 5 years ]
      Will be determined in each treatment. The median estimate to first SSE-FS will be calculated.

    6. Overall response rate (ORR) [ Time Frame: Up to 5 years ]
      Will be defined by RECIST version 1.1. Number and proportion of patients achieving ORR (by RECIST) will be summarized with two-sided 90% CI by treatment arm; comparison between arms will be conducted using chi-square or Fisher's exact test as appropriate.

    TRIAL NUMBER: S1931

    Title: Phase III Trial of Immunotherapy-Based Combination Therapy With or Without Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma (PROBE Trial)

    Purpose: This phase III trial compares the effect of adding surgery to a standard of care immunotherapy-based drug combination versus a standard of care immunotherapy-based drug combination alone in treating patients with kidney cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, pembrolizumab, and avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Surgery to remove the kidney, called a nephrectomy, is also considered standard of care; however, doctors who treat kidney cancer do not agree on its benefits. It is not yet known if the addition of surgery to an immunotherapy-based drug combination works better than an immunotherapy-based drug combination alone in treating patients with kidney cancer.

    TRIAL NUMBER: A031501

    Title: PHASE III RANDOMIZED ADJUVANT STUDY OF MK-3475 (PEMBROLIZUMAB) IN MUSCLE INVASIVE AND LOCALLY ADVANCED UROTHELIAL CARCINOMA (AMBASSADOR) VERSUS OBSERVATION

    Purpose: Primary Outcome Measures: Disease-free survival [ Time Frame: From randomization to the first metastatic recurrence (presence of any recurrent disease), or death, whichever occurs first, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.
    Overall survival [ Time Frame: From randomization to the date of death from any cause, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.

    Secondary Outcome Measures: Disease-free survival in PD-L1 positive and negative patients [ Time Frame: From randomization to the first metastatic recurrence (presence of any recurrent disease), or death, whichever occurs first, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.
    Overall survival in PD-L1 positive and negative patients [ Time Frame: From randomization to the date of death from any cause, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.

    Estimated Enrollment: 739 Actual Study Start Date: September 21, 2017 Estimated Study Completion Date: February 28, 2019 Estimated Primary Completion Date: February 28, 2019 (Final data collection date for primary outcome measure)

    • Children's Hospital - Main Campus
    • Orleans
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    TRIAL NUMBER: AEWS1031

    Title: A PHASE III RANDOMIZED TRIAL OF ADDING VINCRISTINE-TOPOTECAN- CYCLOPHOSPHAMIDE TO STANDARD CHEMOTHERAPY IN INITIAL TREATMENT OF NON-METASTATIC EWING SARCOMA

    Purpose: PRIMARY OBJECTIVES:
    l. To test the effect of the combination of vincristine, cyclophosphamide, and topotecan (VTC) added to the standard 5-drug chemotherapy interval- compressed backbone on event-free survival (EFS) and overall survival of children and young adults with Ewing sarcoma.
    SECONDARY OBJECTIVES:
    I. To evaluate initial volumetric tumor size as a prognostic factor for EFS in patients with localized Ewing tumors.
    II. To evaluate histologic response as a prognostic factor for EFS in patients with localized Ewing tumors.
    III. To continue evaluation of biologic markers both as related to prognosis and as eventual therapeutic targets via encouraging concurrent enrollment on a Ewing sarcoma specimen-collection study.
    IV. To evaluate imaging response by FDG-positron emission tomography (PET) as a prognostic factor for EFS.
    V. To evaluate the effects of the type of local therapy on EFS and overall survival.
    VI. To evaluate the effect of local surgical margins in conjunction with histologic response on EFS in patients with localized Ewing tumors.
    VII. To evaluate the effect of local therapy modality (surgery, radiotherapy, or a combination) as well as the type of surgical reconstruction on musculoskeletal complications.
    OUTLINE: This is a multicenter study. Patients are stratified according to age (= 17 years vs = 18 years) and primary tumor site (pelvic vs non-pelvic vs extra-osseous). Patients are randomized to 1 of 2 treatment arms.
    ARM I:
    INDUCTION THERAPY: Patients receive vincristine sulfate IV on day 1 in weeks 1, 2, 5, 6, 9, and 10; doxorubicin hydrochloride IV on days 1 and 2 and cyclophosphamide IV over 30-60 minutes on day 1 in weeks 1, 5, and 9; and ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 in weeks 3, 7, and 11.
    CONSOLIDATION THERAPY: Patients receive vincristine sulfate on day 1 in weeks 1, 2, 7, 8, 9,10,13,14, 17,18, 21, and 22; doxorubicin hydrochloride IV on days 1 and 2 in weeks 1 and 9; cyclophosphamide IV over 30-60 minutes on day 1 in weeks 1, 7, 9, 13, 17, and 21; and ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 in weeks 3, 5, 11, 15, and 19.
    ARM II:
    INDUCTION THERAPY: Patients receive vincristine sulfate IV on day 1 in weeks 1, 2, 5, 6, 9,10,11 and 12; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1 and 9; cyclophosphamide IV over 15-60 minutes on days 1-5 in weeks 1 and 9, and on day 1 of weeks 5 and 11; ifosfamide and etoposide as in arm I; and doxorubicin hydrochloride IV on days 1 and 2 in weeks 5 and 11.
    CONSOLIDATION THERAPY: Patients receive vincristine sulfate IV on day 1 in weeks 1, 2, 7-10, 13-16, 19, and 20; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1, 7, and 15; cyclophosphamide IV over 15-60 minutes on days 1-5 in weeks 1, 7, and 15, and on day 1 in weeks 9, 13, and 19; ifosfamide IV over 1 hour and etoposide IV over 1- 2 hours on days 1-5 in weeks 3, 5, 11, 17, and 21; and doxorubicin hydrochloride IV on days 1 and 2 in weeks 9,13, and 19.
    Patients with responsive or stable disease undergo may undergo surgery alone in week 13 if lesion can be complete resected with negative margins and with reasonable functional result. Patients with unresectable lesions or inadequate margins after surgery receive radiotherapy during weeks 1-7. Patients with bulky lesions in surgically difficult sites such as the spine, skull, and periacetabular pelvis, patients with a poor response to induction chemotherapy, or those patients in whom surgery would result in unacceptable functional results may undergo radiotherapy alone in weeks 1-7 of consolidation therapy, and surgery should be performed after completion of consolidation chemotherapy. Patients with microscopic residual disease after planned pre-operative radiotherapy receive additional radiotherapy.
    After completion of study therapy, patients are followed up periodically for 10 years.

    TRIAL NUMBER: AEWS1221

    Title: Randomized Phase II Trial Evaluating the Addition of the IGF-1R Monoclonal Antibody Ganitumab (AMG 479, NSC #750008, IND #120449) to Multiagent Chemotherapy for Patients with Newly-Diagnosed Metastatic Ewing Sarcoma

    Purpose: PRIMARY OBJECTIVES:
    I. To compare the event-free survival (EFS) in patients with newly diagnosed metastatic Ewing sarcoma treated with multiagent chemotherapy with and without the addition of ganitumab (AMG 479).
    SECONDARY OBJECTIVES:
    I. To describe the toxicity of the addition of ganitumab to multimodality therapy for patients with newly diagnosed metastatic Ewing sarcoma.
    TERTIARY OBJECTIVES:
    I. To compare bone marrow response rates and overall survival in patients with newly diagnosed metastatic Ewing sarcoma treated with multiagent chemotherapy with and without the addition of ganitumab.
    II. To describe the toxicity of 6 months of ganitumab monotherapy as Maintenance therapy following multimodality therapy in patients with newly diagnosed metastatic Ewing sarcoma.
    III. To describe trough levels of ganitumab in a cohort of patients with Ewing sarcoma < 21 years of age treated with 18 mg/kg.
    IV. To describe the feasibility of and local failure rates following hypofractionated stereotactic body radiotherapy (SBRT) directed at bone metastases in patients with newly diagnosed metastatic Ewing sarcoma.
    V. To determine if EFS, overall survival, bone marrow response rates, and toxicity differ based on serum markers of the insulin-like growth factor 1 (IGF-1) pathway in patients with newly diagnosed metastatic Ewing sarcoma treated with interval compressed chemotherapy with and without the addition of ganitumab.
    VI. To determine if EFS, overall survival, and bone marrow response rates differ based on tumor IGF-1 receptor (IGF-1R), insulin receptor, and epidermal growth factor receptor (EGFR) pathway components in patients with newly diagnosed metastatic Ewing sarcoma treated with interval compressed chemotherapy with and without the addition of ganitumab.
    VII. To evaluate bone marrow micrometastatic disease and tumor cell surface IGF-1R expression at diagnosis and after 3 and 6 cycles of study therapy in patients with newly diagnosed metastatic Ewing sarcoma.
    VIII. To determine if the presence of germline polymorphisms in EGFR correlate with response to multiagent therapy with and without ganitumab.
    IX. To investigate the ability of fludeoxyglucose F 18-positron emission tomography (FDG-PET) to augment conventional response assessment of primary Ewing sarcoma tumors by magnetic resonance imaging (MRI).
    X. To explore FDG-PET response at the primary tumor as a prognostic marker and as a predictive biomarker of clinical activity of IGF-1R inhibition in patients with newly diagnosed metastatic Ewing sarcoma.
    OUTLINE: Patients are randomized to 1 of 2 treatment regimens.
    REGIMEN A (vincristine sulfate, doxorubicin hydrochloride and cyclophosphamide [VDC] and ifosfamide and etoposide [IE]):
    INDUCTION THERAPY: Patients receive vincristine sulfate intravenously (IV) over 1 minute on day 1; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2; and cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 5, and 9; and ifosfamide IV over 1 hour on days 1 to 5 and etoposide IV over 1-2 hours on days 1 to 5 of weeks 3, 7, and 11.
    LOCAL CONTROL THERAPY: Between weeks 13-18, patients undergo surgery and/or radiation therapy.
    CONSOLIDATION THERAPY: Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1, 7, 9, and 13; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 1 and 7; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 7, 9, and 13; ifosfamide IV over 1 hour on days 1 to 5 of weeks 3, 5, 11, and 15; and etoposide IV over 1-2 hours on days 1 to 5 of weeks 3, 5, 11, and 15.
    METASTATIC SITE IRRADIATION: Patients with lung metastases undergo definitive SBRT or external beam radiation therapy (EBRT) over 5 days.
    REGIMEN B (VDC/IE + ganitumab):
    INDUCTION THERAPY: Patients receive Induction therapy as in Regimen A and receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 1, 3, 5, 7, 9, and 11.
    LOCAL CONTROL THERAPY: Between weeks 13-18, patients undergo surgery and/or radiation therapy.
    CONSOLIDATION THERAPY: Patients receive Consolidation therapy as in Regimen A and ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 7, 9, 11, 13, and 15.
    METASTATIC SITE IRRADIATION: Patients with lung metastases undergo definitive SBRT or EBRT over 5 days.
    MAINTENANCE THERAPY: Patients receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 in weeks 1, 4, 7, 10, 13, 16, 19, and 22.
    After completion of study treatment, patients are followed up every 3 months for 3 years and every 6 months for 2 years.

    TRIAL NUMBER: ACNS02B3

    Title: A CHILDREN'S ONCOLOGY GROUP PROTOCOL FOR COLLECTING AND BANKING PEDIATRIC BRAIN TUMOR RESEARCH SPECIMENS

    Purpose: OBJECTIVES:
    ?Collect brain tumor tissue and an accompanying blood sample from pediatric patients with brain tumors treated at Children's Oncology Group institutions. ?Provide a repository for long-term storage of specimens from these patients. ?Make these specimens available to qualified researchers to understand the biology of pediatric brain tumors. OUTLINE: This is a multicenter study
    Brain tumor tissue and blood specimens are collected from patients and banked for future study.
    PROJECTED ACCRUAL: An unlimited number of specimens will be collected.

    TRIAL NUMBER: ACNS0831

    Title: PHASE III RANDOMIZED TRIAL OF POST-RADIATION CHEMOTHERAPY IN PATIENTS WITH NEWLY DIAGNOSED EPENDYMOMA AGES 1 TO 21 YEARS

    Purpose: PRIMARY OBJECTIVES:
    I. To determine the event-free survival (EFS) and overall survival (OS) of children with completely resected ependymoma treated with maintenance chemotherapy comprising vincristine sulfate, cisplatin, etoposide, and cyclophosphamide (VCEC) versus observation following post- operative conformal radiotherapy (cRT).
    SECONDARY OBJECTIVES:
    I. To estimate the EFS and OS of children with incompletely resected ependymoma who are unable to achieve a complete response (CR) by post-operative induction chemotherapy or by second surgery who are non-randomly assigned to cRT followed by VCEC.
    II. To further evaluate the EFS and OS of children with supratentorial classic ependymoma who achieve a complete resection at first or second resection or children who achieve a CR to short-course induction chemotherapy following first surgery.
    III. To determine the neurologic, neuropsychological, and endocrine long-term sequelae of surgery, cRT, and VCEC as compared to those patients treated on COG-ACNS0121.
    IV. To determine biologic prognostic factors in childhood ependymoma by utilizing genomic profiles via comparative genomic hybridization and single-nucleotide polymorphism arrays, and microarray gene expression profiling analysis on initial tumor samples and correlating this with clinical outcome.
    V. To evaluate prognostic immune-function gene expression in ependymomas. VI. To build upon the data derived from COG- ACNS0121 to develop genotypically based classification signatures and to correlate these to WHO grade, location, extent of resection, treatment, EFS, and OS.
    VII. To evaluate telomere maintenance as a prognostic marker.
    OUTLINE: This is a multicenter study. Patients are stratified according to extent of resection at initial surgery (total vs near total resection), tumor histology, and tumor location (infratentorial primary tumor vs supratentorial anaplastic tumor). Patients are randomized to 1 of 2 treatment arms. Patients with supratentorial classic tumor are assigned to arm II.
    All patients receive induction chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 15-60 minutes on day 1, and cyclophosphamide IV over 30-60 minutes on days 1-2. Patients also receive etoposide IV over 60-120 minutes on days 1-3 of course 2 only. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease, partial response, or locally progressive disease and who are deemed potentially resectable undergo surgery within 15 days after completion of induction chemotherapy.
    ARM I: Patients undergo conformal radiotherapy over 6-7 weeks. Patients then receive vincristine sulfate IV on days 1, 8, and 15 (courses 1-3 only); etoposide IV over 1-2 hours on days 1-3; cisplatin IV over 1-8 hours on day 1; and cyclophosphamide IV over 30-60 minutes on days 1-2. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
    ARM II: Patients undergo conformal radiotherapy over 6-7 weeks. Some patients undergo blood and tissue sample collection before treatment and after surgery for gene expression microarray, genomic hybridization array, and other correlative studies.
    After completion of study therapy, patients are followed up every 4 months for 5 years.

    TRIAL NUMBER: ACNS1022

    Title: A Phase II Randomized Trial of Lenalidomide (NSC #703813, IND #70116) in Pediatric Patients with Recurrent, Refractory or Progressive Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas

    Purpose: PRIMARY OBJECTIVES:
    I. To determine the objective response rate in children with recurrent, refractory, or progressive juvenile pilocytic astrocytomas and optic pathway gliomas who are treated with Regimen A low-dose (20 mg/m^2/dose) or Regimen B high-dose (115 mg/m^2/dose) lenalidomide.
    SECONDARY OBJECTIVES:
    I. To estimate the event-free survival (EFS) (based on standard two-dimensional tumor measurements, determined by each institution) of children with recurrent, refractory, or progressive juvenile pilocytic astrocytomas and optic pathway gliomas who are treated with lenalidomide.
    II. To compare response categories and EFS across the 3 magnetic resonance (MR) sequences (T2-weighted, fluid attenuated inversion recovery [FLAIR], T1-weighted post-contrast).
    III. To correlate steady-state pharmacokinetics of lenalidomide (1 sample obtained between days 5-21) with objective response and EFS.
    IV. To evaluate toxicities of long-term lenalidomide use.
    OUTLINE: Patients are randomized to 1 of 2 treatment arms.
    ARM I (Regimen A): Patients receive low-dose lenalidomide orally (PO) once daily (QD) on days 1-21. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
    ARM II (Regimen B): Patients receive high-dose lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
    After completion of study treatment, patients are followed up annually for approximately 3 years.

    TRIAL NUMBER: ACNS1123

    Title: PHASE 2 TRIAL OF RESPONSE-BASED RADIATION THERAPY FOR PATIENTS WITH LOCALIZED CENTRAL NERVOUS SYSTEM GERM CELL TUMORS (CNS GCT)

    Purpose: PRIMARY OBJECTIVES:
    I. To determine, as measured by the 3-year progression-free survival (PFS) rate and patterns of failure, whether dose and volume of irradiation can be safely reduced to 30.6 Gy whole ventricular-field irradiation (WVI) plus 23.4 Gy primary site boost instead of 36 Gy craniospinal irradiation (CSI) plus primary site boost in the subgroup of children and young adults with localized nongerminomatous germ cell tumor (NGGCT) who have a magnetic resonance imaging (MRI) and tumor marker criteria (CSF and serum) for confirmed complete response (CR) or partial response (PR) to induction chemotherapy and negative serum and cerebrospinal fluid (CSF) tumor markers OR in patients who have less than a PR after induction chemotherapy with negative tumor markers who undergo a second-look surgery and are found to have only mature teratoma, residual scar or fibrosis, and fit the definition of CR/PR after second-look surgery.
    II. To determine, as measured by the 3-year PFS rate and patterns of failure, whether simplified chemotherapy followed by dose-reduced radiation therapy is effective for treating children and young adults with localized primary central nervous system (CNS) germinoma who present with serum and/or CSF human chorionic gonadotropin-beta (hCGß) =< 50 mIU/mL.
    III. To prospectively evaluate and longitudinally model the cognitive, social, and behavioral functioning of children and young adults who are treated with reduced radiation dose and volume of irradiation in Stratum 1 (NGGCT) and with dose-reduced radiation therapy in Stratum 2 (Germinoma) using the ALTE07C1 protocol (This objective will be assessed independently for the two strata).
    SECONDARY OBJECTIVES:
    To estimate the PFS and overall survival (OS) distributions of patients with NGGCT treated with 30.6 Gy WVI and involved-field radiation therapy (IFR) focal boost to 54 Gy. II. To estimate the PFS and OS distributions of localized- germinoma patients who present with serum and/or CSF hCGß = 50 mIU/mL vs serum and/or CSF hCGß > 50 mIU/mL and =< 100 mIU/mL.
    OUTLINE: This is a multicenter study. Patients are stratified according to localized primary disease (nongerminomatous germ cell tumor [NGGCT] vs germinoma).
    Stratum 1 (NGGCT): Patients receive induction therapy comprising carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 1-2 hours on days 1-3 of courses 1, 3, and 5. Patients also receive ifosfamide IV over 1 hour and etoposide over 1-2 hours on days 1-5 of courses 2, 4, and 6. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responsive disease (complete [CR] or partial response [PR]) to induction chemotherapy undergo radiotherapy once daily (QD) 5 days a week for 6 weeks. Patients with PR, stable disease (SD), or progressive disease (PD) and normalization of tumor levels undergo second-look surgery. Patients who achieve CR or PR after second-look surgery undergo radiotherapy.
    Stratum 2 (Germinoma): Patients receive induction therapy comprising carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with CR or continued CR undergo radiotherapy QD 5 days a week for approximately 4 weeks. Patients with PR, SD, or PD with normal tumor markers may undergo second-look surgery. Patients found to have mature teratoma or non-viable tumor during surgery undergo radiotherapy. Patients with PR or SD with residual disease (=< 1.5 cm) and suprasellar (> 0.5 cm) or pineal (> 1 cm) involvement and normal tumor markers undergo radiotherapy after chemotherapy without second-look surgery.
    After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 2 years, and then annually for up to 3 years.

    TRIAL NUMBER: ACNS1422

    Title: A Phase 2 Study of Reduced Therapy for Newly Diagnosed Average-Risk WNT-Driven Medulloblastoma Patients

    Purpose: Primary Outcome Measures: PFS [ Time Frame: From the initiation of protocol treatment to the occurrence of any of the following events: disease progression or disease recurrence or death from any cause, assessed up to 10 years ] PFS along with the confidence intervals will be estimated using the Kaplan-Meier method. PFS will also be reported based on central radiology review.

    Secondary Outcome Measures: Change in neurocognitive function (cognitive, social, emotional and behavioral) according to Children Oncology Group Standard Neuropsychological Battery [ Time Frame: Baseline to up to 60 months post-diagnosis ] Neurocognitive function will be measured at 9, 30 and 60 months post diagnosis and will be compared with the neurocognitive outcomes from an age and gender matched ACNS0331 cohort to the WNT patients treated on ACNS1422. Data for all assessments will be available as standardized t-scores. The change over time for each component of the neuropsychological testing will be estimated using the Generalized Estimating Equation (GEE) approach, with the standardized t-scores as the dependent variable and the assessment times as a covariate. Within the ACNS1422 cohort GEE models will also be used to exp
    DNA methylation profiling as real-time classification of WNT-driven medulloblastoma [ Time Frame: Within 32 days of definitive surgery ] Results will be compared to the results of the molecular screening tests. The sensitivity and specificity comparison between DNA methylation arrays and the standard methods (molecular screening tests for WNT using IHC and CTNNB1 sequencing) will be performed using McNemar's test.

    Other Outcome Measures: DNA methylation profiling of medulloblastoma real-time" predictive classification scheme for the SHH, group 3 and group 4 medulloblastoma subgroups according to the Heidelberg classifier [ Time Frame: Within 32 days of definitive surgery ] The proportion of patients classified into each medulloblastoma subgroup in "real time" will be reported.

    Estimated Enrollment: 45 Study Start Date: October 2016 Estimated Primary Completion Date: May 2025 (Final data collection date for primary outcome measure)

    TRIAL NUMBER: ANBL00B1

    Title: NEUROBLASTOMA BIOLOGY STUDIES

    Purpose:

    TRIAL NUMBER: ANBL1232

    Title: Utilizing Response- and Biology-Based Risk Factors to Guide Therapy in Patients with Non-High-Risk Neuroblastoma; A Groupwide Historically-Controlled Phase III Study

    Purpose: PRIMARY OBJECTIVES:
    I. To eliminate therapy as the initial approach for infants < 12 months of age with small International Neuroblastoma Risk Group (INRG) stage L1 neuroblastoma while maintaining an overall survival (OS) of 99%.
    II. To eliminate therapy as the initial approach for non-high-risk patients < 18 months of age with localized neuroblastoma and favorable biology (histologic and genomic features) while maintaining an OS of 99%.
    III. To achieve a 3-year OS of > 81% for infants < 18 months of age with INRG stage Ms neuroblastoma using objective criteria for early initiation of a response-based treatment algorithm.
    IV. To achieve a 3-year event free survival (EFS) of > 70% for non-high-risk infants < 12 months of age with INRG stage M neuroblastoma and unfavorable biology (histologic and/or genomic features) through the addition of isotretinoin therapy.
    SECONDARY OBJECTIVES:
    I. To describe the time to intervention or tumor progression, type of intervention and site of progression for patients with localized neuroblastoma who experience progression after an initial period of observation.
    II. To characterize the pharmacokinetic profile of the chemotherapeutic agents carboplatin and etoposide in patients with stage Ms disease.
    III. To define the genomic profile of tumors from patients with non-high-risk neuroblastoma both at initial biopsy and at the time of subsequent biopsy or surgical resection.
    IV. To describe the histology of tumor specimens obtained at the time of subsequent biopsy or surgical resection.
    V. To determine the salvage rate (OS) of patients with tumor relapse or disease progression.
    VI. To determine the procedural complication rate (initial biopsy, resection [intraoperative and postoperative], subsequent biopsy) and correlate with the degree of surgical resection.
    VII. To determine the rate of reduction in image defined risk factors (IDRF) in L2 tumors following observation or chemotherapy.
    VIII. To describe bone abnormalities on bilateral tibial radiographs obtained before and after isotretinoin therapy.
    IX. To determine the variability of isotretinoin pharmacokinetics and relationship to pharmacogenomic parameters and determine if these levels and/or genetic variations correlate with EFS or systemic toxicity.
    OUTLINE: Patients are assigned to 1 of 4 treatment groups.
    GROUP A: Patients undergo clinical observation for 96 weeks.
    GROUP B: Patients undergo clinical observation for 3 years in the absence of disease progression. Upon disease progression, patients undergo surgery or receive first-line chemotherapy comprising carboplatin intravenously (IV) over 1 hour on day 1 (courses 1, 2, 4, 6, and 7), etoposide IV over 1 hour on days 1-3 (courses 1, 3, 4, 5, and 7), cyclophosphamide IV over 1 hour on day 1 (courses 2, 3, 5, 6, and 8), and doxorubicin hydrochloride IV over 15 minutes on day 1 (courses 2, 4, 6 and 8). Treatment with chemotherapy repeats every 21 days for 2-8 courses in the absence of disease progression or unacceptable toxicity. Once a partial response (PR) or better is achieved, patients undergo clinical observation for 3 years.
    GROUP C: Patients at high risk for deterioration and a poor outcome immediately receive first-line chemotherapy as in Group B. All other patients undergo clinical observation for 3 years in the absence of disease progression. Upon disease progression, patients receive first-line chemotherapy as in Group B. Once a PR or better is achieved, patients undergo clinical observation for 3 years.
    GROUP D: Patients receive first-line chemotherapy as in Group B. Patients who achieve a complete response (CR) or very good partial response (VGPR) following first-line chemotherapy receive isotretinoin orally (PO) twice daily (BID) on days 1-14. Treatment with isotretinoin repeats every 28 days for 6 courses. Patients then undergo clinical observation for 3 years. Patients who achieve a PR or stable disease (SD) following first-line chemotherapy receive salvage chemotherapy comprising cyclophosphamide IV over 30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment with salvage chemotherapy repeats every 21 days for 2-6 courses. Patients then receive isotretinoin PO BID on days 1-14. Treatment with isotretinoin repeats every 28 days for 6 courses. Patients then undergo clinical observation for 3 years.
    After completion of study treatment, patients are followed up annually for 5 years.

    TRIAL NUMBER: AAML08B1

    Title: BIOLOGY STUDY OF TRANSIENT MYELOPROLIFERATIVE DISORDER (TMD) IN CHILDREN WITH DOWN SYNDROME (DS)

    Purpose: OBJECTIVES:
    •To further our biological understanding of the natural history of transient myeloproliferative disorder (TMD) and its relationship to subsequent leukemia by facilitating the development of a TMD cell and protein bank, and repository of DNA/RNA from megakaryoblasts for future biological studies. •To investigate the biology of TMD molecular changes associated with resolution of TMD or its conversion to acute myeloid leukemia within each mortality-risk group by conducting GATA1 mutational analyses, hematopoiesis clonality studies, assessment of RAS mutations, and genomic instability studies using glycophorin A assays. •To determine if high-resolution microarray genomic analysis of TMD blasts (using Affymetrix SNP Genechip technology to assess gene expression, copy number variation, and loss of heterozygosity) can predict the development of subsequent leukemia. •To determine the relationship of minimal residual disease (monitored by peripheral blood flow cytometry and GATA1 mutational studies) to clinical remission status and development of subsequent leukemia within each mortality-risk group of TMD patients. •To evaluate the relationship between karyotype (including FISH analysis) and subsequent leukemia in TMD patients. •To examine pharmacogenetics and in vitro drug sensitivity to cytarabine (MTT assay) in blasts from TMD patients. •To examine the relationship of functional polymorphisms in Phase I and Phase II drug detoxification genes, DNA repair, and DNA synthesis pathways that may modify susceptibility to leukemia and outcome in TMD patients. •To determine the relationship between fibrosis-associated serum factors (e.g., platelet-derived growth factor, transforming growth factor beta, N-terminal peptide of III procollagen, type IV collagen, and hyaluronic acid) and event-free survival. OUTLINE: This is a multicenter study.
    Patients undergo peripheral blood collection periodically for biomarker analysis. Samples are analyzed for GATA1 mutations by real-time PCR, polymorphisms, cytogenetics, - and K-RAS mutations, gene expression, drug sensitivity patterns, and minimal residual disease by flow cytometry.
    Patients are followed up periodically for 5 years.

    TRIAL NUMBER: ALTE03N1

    Title: KEY ADVERSE EVENTS AFTER CHILDHOOD CANCER

    Purpose: PRIMARY OBJECTIVES:
    I. To identify key adverse events developing in patients (cases) with a primary cancer diagnosed at age 21 or younger.
    II. To characterize the key adverse events with respect to the nature of the primary malignancy (pathology, stage) and coded details of the therapeutic protocol.
    III. To identify treatment-related and demographic risk factors through a direct comparison of the case-group and controls identified from the remaining patients with the same primary diagnosis.
    IV. To compare the frequency of mutations or polymorphisms in specific candidate genes in cases and controls, using constitutional DNA and RNA from the cases and controls.
    V. To explore the role and nature of gene-environment interaction in the development of key adverse events.
    OUTLINE: This is a multicenter study.
    DNA from peripheral blood or buccal sample of patients is analyzed for the presence of polymorphisms in candidate genes associated with an increased risk of late-occurring complications, such as cardiac dysfunction (closed to accrual as of 4/17/09), myocardial infarction (closed to accrual as of 6/5/06), ischemic stroke, avascular necrosis (closed to accrual as of 11/26/08), and subsequent malignant neoplasms.
    Patients also complete a questionnaire detailing family history and health history.

    TRIAL NUMBER: CHDCP-001

    Title: DCP-001, Use of a Clinical Trial Screening Tool to Address Cancer Health Disparities in the NCI Community Oncology Research Program (NCORP)

    Purpose:

    TRIAL NUMBER: ANBL1531

    Title: ANBL1531, A Phase 3 Study of 131I-Metaiodobenzylguanidine (131I-MIBG) or Crizotinib Added to Intensive Therapy for Children with Newly Diagnosed High-Risk Neuroblastoma (NBL) (IND# 134379)

    Purpose: ANBL1531 is a COG group-wide Phase III study for patients between 1-30 years of age with neuroblastoma or ganglioneuroblastoma (nodular). In this study, researchers want to find out if we can improve the treatment for subjects with high-risk NBL by adding the experimental drug 131I-MIBG or the experimental drug crizotinib to COG recommended therapy. (Subjects are people who agree to take part in this study). 131I-MIBG is an experimental anticancer drug that has not been approved by the Food and Drug Administration (FDA) for use in treating high-risk NBL. 131I-MIBG has been used to treat NBL that did not respond to standard therapy or that has come back. 131I-MIBG has been shown to be well tolerated in children with cancer. Crizotinib is an experimental anticancer drug that has not been approved by the FDA for use in treating high-risk NBL. Crizotinib has been approved by the FDA for use in treating adults with certain types of lung cancer that has spread. Crizotinib has been welltolerated in children and adults with cancer. Crizotinib will only be used in subjects whose tumor shows changes (mutations or increased number of copies) in a gene called ALK. Changes in the ALK gene are only found in 10-15% of children with high-risk NBL. The overall goals of this study are to: • Compare the effects, good and/or bad, of the experimental drug 131I-MIBG added to current COG recommended therapy to the effects of current COG recommended therapy without the experimental drug 131I-MIBG. • Compare the effects, good and/or bad, of the experimental drug crizotinib added to current COG recommended therapy to the effects of current COG recommended therapy without the experimental drug crizotinib. Another goal of this study is to: • Evaluate the effects, good and/or bad, of using the experimental drug 131I-MIBG and reducing the number of stem cell transplants from 2 to 1 by giving the drugs BuMel during Consolidation therapy. The goal for subjects in Arm D of this study is: • To see if subjects with a tumor that is 123I-MIBG non-avid and does not have changes in the ALK gene have better outcomes than those with 123I-MIBG avid NBL when treated with COG recommended therapy for high-risk neuroblastoma. An 123I-MIBG avid tumor means that the tumor took up 123I-MIBG during a scan. An 123IMIBG non-avid tumor means that the tumor did not take up 123I-MIBG during a scan. The goal for subjects in Arm E of this study is: • To see if subjects with a tumor that shows changes in the ALK gene will have improved outcomes when the experimental drug crizotinib is added to COG recommended therapy for high-risk neuroblastoma. Each subject on the ANBL1531 study will have genetic tests done on his/her tumor tissue. The tumor tissue will be tested for changes to a gene called ALK. The experimental drug crizotinib may be effective against tumors with ALK gene changes.

    TRIAL NUMBER: APEC14B1

    Title: Project: Every Child for Younger Patients With Cancer

    Purpose: This research trial studies the Project: Every Child for younger patients with cancer. Gathering health information over time from younger patients with cancer may help doctors find better methods of treatment and on-going care.

    TRIAL NUMBER: ARST1431

    Title: COG ARST1431, A Randomized Phase 3 Study of Vincristine, Dactinomycin, Cyclophosphamide (VAC) Alternating with Vincristine and Irinotecan (VI) Versus VAC/VI Plus Temsirolimus (TORI, Torisel, NSC# 683864, IND# 122782) in Patients with Intermediate Risk (IR) Rhabdomyosarcoma (RMS)

    Purpose: ARST1431, states that Unfortunately about 25% of patients with intermediate-risk (IR) embryonal rhabdomyosarcoma (ERMS) and 50% of those with IR alveolar rhabdomyosarcoma (ARMS) will experience disease recurrence with a resulting long-term event-free survival (EFS) of 65%. The mTOR pathway is important in RMS biology, and temsirolimus (TORI), an mTOR inhibitor, has demonstrated clinical activity in patients with relapsed RMS. In an attempt to improve long-term survival for patients with IR RMS, ARST1431 will compare the EFS of patients with newly diagnosed IR RMS randomly assigned to standard vincristine, dactinomycin, and cyclophosphamide (VAC) alternating with vincristine and irinotecan (VI) versus VAC/VI plus TORI. Radiotherapy will start at Week 13 of therapy for all patients. Correlative biology studies will be performed including a determination of the FOXO1 gene fusion status in the tumor and impact on patient outcome. Children’s Hospital/LSUHSC-NO sees several diagnosed patients with Intermediate Risk (IR) Rhabdomyosarcoma (RMS), We estimate seeing up to 5-10 patients per year.

    TRIAL NUMBER: ACCL1033

    Title: A Comprehensive Approach to Improve Medication Adherence in Pediatric ALL

    Purpose: PRIMARY OBJECTIVES:
    I. Determine the impact of interventions proposed in intervention program (IP) vs. education alone (EDU) on adherence to oral 6MP (mercaptopurine) in children with acute lymphoblastic leukemia (ALL). Adherence will be measured by: i) Medication Event Monitoring Systems (MEMS) (primary measure of adherence to oral 6MP, providing real-time data; ii) red cell thioguanine nucleotide (TGN) levels (providing data on chronic, systemic 6MP exposure).
    SECONDARY OBJECTIVES:
    I. Examine the modifying effect of sociodemographic and psychosocial variables, and the mediating effect of health beliefs/ knowledge on change in adherence with intervention.
    II. Determine impact of IP vs. EDU on risk of relapse of ALL.
    OUTLINE: Patients are randomized to 1 of 2 intervention arms.
    ARM I: Patients receive the Patients Supply Kit containing an electronic pill monitoring system, a MEMS® medication bottle with TrackCap? with standard resistant cap, and written instructions for the patient and pharmacist. Parents and/or caregivers are also trained to supervise patients' intake of the medication. Beginning on day 1, patients start using the MEMS® medication bottle with TrackCap?. Clinical research assistants contact patients and parents by telephone the next day to confirm that TrackCap? is being used, to identify any obstacles, and to determine solutions. Beginning on day 29, patients and caregivers view an interactive multimedia educational program on-line or via DVD. Patients also receive a customized electronic mercaptopurine schedule and automated customized text message reminders delivered via cellular phone or web-based interface. Patients and caregivers are instructed to return the MEMS® medication bottle with TrackCap? to the clinic by day 141.
    ARM II: Patients receive the usual standard of care and the mercaptopurine from the MEMS® medication bottle with TrackCap? as patients in arm I.
    After completion of study treatment, patients are followed up every 6 months for 5 years and then annually until 10 years from diagnosis.

    TRIAL NUMBER: AHOD1331

    Title: A Randomized Phase III Study of Brentuximab Vedotin (Bv, IND #117117) for Newly-Diagnosed High-Risk Classical Hodgkin Lymphoma (cHL) in Children and Adolescents

    Purpose: PRIMARY OBJECTIVES:
    I. To assess the event free survival (EFS) of a novel regimen incorporating brentuximab vedotin (Bv; Adcetris) in the chemotherapy backbone of doxorubicin (Adriamycin) (doxorubicin hydrochloride), vincristine (vincristine sulfate), etoposide, prednisone and cyclophosphamide (Bv-AVEPC) in newly diagnosed high-risk classical Hodgkin lymphoma (cHL) compared to those treated with Adriamycin, bleomycin sulfate, vincristine sulfate, etoposide, prednisone, and cyclophosphamide (ABVE-PC).
    SECONDARY OBJECTIVES:
    I. To determine whether children/adolescents with high-risk cHL treated with Bv-AVEPC have a higher rate of early response (determined by fludeoxyglucose F 18 [FDG]-positron emission tomography [PET]) and a reduction in protocol directed radiation therapy (RT) compared to those treated with ABVE-PC.
    II. To compare the rate of neuropathy (>= grade 3) among patients treated on the Bv-AVEPC (experimental arm) to patients treated on the ABVE-PC (standard arm).
    TERTIARY OBJECTIVES:
    I. To validate and compare the Childhood Hodgkin International Prognostic Score (CHIPS) to conventional Ann Arbor Stage (Stages II B with bulk, III B, IV A or B) in predicting outcome in high-risk childhood cHL.
    II. To determine the incidence of preferentially expressed antigen in melanoma (PRAME) and testis-specific antigens in Epstein-Barr virus (EBV)- cHL tumors and the incidence of EBV antigens (Epstein-Barr nuclear antigen 1 [EBNA1], Epstein-Barr virus latent membrane protein 1 [LMP1], large multifunctional peptidase 2 [LMP2]) in EBV+ cHL tumors, with the goal of developing strategies to integrate cellular therapy into treatment for newly diagnosed high-risk cHL. (Biology) III. To incorporate qualitative visual FDG-PET into response-directed treatment algorithms and explore quantitative FDG-PET and computed tomography (CT) definitions of tumor burden and response for incorporation into next generation pediatric cHL risk-stratification schemes. (Imaging) IV. To evaluate the reduction in normal tissue irradiation associated with the current treatment approach compared to the volume of historic involved field radiation therapy (IFRT) fields. (Radiation Therapy) V. To evaluate EFS and patterns of relapse following protocol-specified RT utilization and treatment volumes. (Radiation Therapy) VI. To characterize the extent of chemotherapy induced peripheral neuropathy (CIPN), as reported by patients and parent proxies, through serial administration of the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-NTX). (Patient Reported Outcomes [PRO] of Peripheral Neuropathy and Health-Related Quality of Life) VII. To describe the Health-Related Quality of Life (HRQL) consequences of peripheral neuropathy over time by correlating total neuropathy scale scores with the individual items with the Child Health Ratings Inventories (CHRIs)-Global scale (e.g., physical health, pain, emotional functioning). (PRO of Peripheral Neuropathy and Health-Related Quality of Life) VIII. To perform a cross validation of the FACT-GOG-NTX with the Total Neuropathy Score-Pediatric Vincristine (TNS-PV) to determine the performance of both measures with the use of brentuximab vedotin in a limited institutional approach in children and adolescents with cHL. (PRO of Peripheral Neuropathy and Health-Related Quality of Life) IX. To assess the resource use and cost implications of Bv in combination with chemotherapy and radiotherapy for newly diagnosed high-risk cHL in children and adolescents. (Economic)
    OUTLINE: Patients are randomized to 1 of 2 treatment arms.
    ARM I (ABVE-PC): Patients receive doxorubicin hydrochloride intravenously (IV) over 1-15 minutes on days 1-2, bleomycin sulfate IV over 10 minutes or subcutaneously (SC) on days 1 and 8, vincristine sulfate IV over 1 minute on days 1 and 8, etoposide IV over 60-120 minutes on days 1-3, prednisone orally (PO) twice daily (BID) on days 1-7, and cyclophosphamide IV over 30-60 minutes on days 1 and 2.
    ARM II (Bv-AVEPC): Patients receive brentuximab vedotin IV over 30 minutes on day 1. Patients also receive doxorubicin hydrochloride, etoposide, prednisone, and cyclophosphamide as in Arm I and vincristine sulfate IV over 1 minute on day 8.
    In both arms, treatment repeats every 21 days for 5 courses in the absence of disease progression or unacceptable toxicity.
    After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 30, 36, and 48 months.

    TRIAL NUMBER: 9442/4941L

    Title: NATIONAL WILMS TUMOR LATE EFFECTS STUDY

    Purpose:

    TRIAL NUMBER: AREN03B2

    Title: RENAL TUMORS CLASSIFICATION, BIOLOGY, AND BANKING STUDY

    Purpose: PRIMARY OBJECTIVES:
    I. Classify patients with renal tumors by histological categorization, surgico- pathological stage, presence of metastases, age at diagnosis, tumor weight, and loss of heterozygosity for chromosomes 1p and 16q, to define eligibility for a series of therapeutic studies.
    II. Maintain a biological samples bank to make specimens available to scientists to evaluate additional potential biological prognostic variables and for the conduct of other research by scientists.
    SECONDARY OBJECTIVES:
    I. Monitor outcome for those patients who are not eligible for a subsequent therapeutic study.
    II. Describe whether the pulmonary tumor burden correlates with outcome in patients with stage IV disease.
    III. Describe the sensitivity and specificity of abdominal computed tomography (CT) scan by comparing it with surgical and pathologic findings for identification of local tumor spread beyond the renal capsule to adjacent muscle and organs, lymph node involvement at the renal hilum and in the retroperitoneum, preoperative tumor rupture, and metastases to the liver.
    IV. Compare the sensitivity and specificity of pre-operative abdominal CT scan and MRI for the identification and differentiation of nephrogenic rests and Wilms' tumor in children with multiple renal lesions.
    V. Correlate the method of conception (natural vs assisted reproductive technology) with the development of Wilms' tumor.
    OUTLINE: This is a multicenter study.
    Tumor tissue, blood, and urine samples are collected for research studies, including immunohistochemistry. CT scans and magnetic resonance imaging (MRIs) are also performed. Loss of heterozygosity analyses (chromosome 1p and 16q) are performed by extraction of DNA. DNA polymorphisms are assayed by polymerase chain reaction using standard methodology. Leftover specimens are archived for future studies.
    Patients are followed periodically for 5 years.

    TRIAL NUMBER: AAML1031

    Title: A PHASE III RANDOMIZED TRIAL FOR PATIENTS WITH DE NOVO AML USING BORTEZOMIB (IND# 58443, NSC# 681239) AND SORAFENIB (BAY 43-9006, IND#69896, NSC# 724772) FOR PATIENTS WITH HIGH ALLELIC RATIO FLT3/ITD

    Purpose: PRIMARY OBJECTIVES:
    I. To compare event-free survival (EFS) and overall survival (OS) of patients with de novo acute myeloid leukemia (AML) with or without high allelic ratio FLT3/ITD+ mutations who are randomized to standard therapy versus bortezomib/standard combination therapy.
    II. To determine the feasibility of combining bortezomib with standard chemotherapy in patients with de novo AML.
    III. To compare the OS and EFS of high-risk patients treated with intensive Induction II with historical controls from COG-AAML03P1 and COG- AAML0531.
    IV. To determine the feasibility of combining sorafenib with standard chemotherapy in patients with de novo high allelic ratio FLT3/ITD+ AML.
    SECONDRY OBJECTIVES:
    I. To assess the anti-leukemic activity of sorafenib in patients with de novo high allelic ratio FLT3/ITD+ AML.
    II. To compare the percentage of patients converting from positive MRD to negative MRD after Intensive Induction II with historical controls from COG- AAML03P1 and COG-AAML0531.
    III. To compare OS, disease-free survival (DFS), cumulative incidence of relapse, and treatment-related mortality from end of Intensification I between patients allocated to best allogenic donor stem cell transplant (SCT) and comparable patients on COG-AAML0531 who did not receive allogenic donor SCT.
    IV. To compare OS, DFS, cumulative incidence of relapse, treatment-related mortality, and severe toxicity between patients allocated to matched family donor SCT on COG-AAML103P1 and COG-AAML0531.
    V. To assess the health-related quality of life (HRQOL) of patients treated with chemotherapy and SCT for AML.
    VI. To compare the changes in shortening fraction/ejection fraction over time between patients treated with and without dexrazoxane.
    VII. To refine the use of minimal-residual disease (MRD) detection with 4- color flow cytometry.
    VIII. To evaluate the prognostic significance of molecular MRD and its contribution to risk identification with multidimensional flow cytometry (MDF)-based MRD in patients with translocations amenable to quantitative RT-PCR (e.g., t(8;21), inv(16), t(9;11), WT1 expression).
    IX. To determine the leukemic involvement of the hematopoietic early progenitor cell and its role in defining response to therapy.
    X. To define the leukemic stem cell population in patients with AML. XI. To determine the prevalence and prognostic significance of molecular abnormalities of WT1, RUNX1, MLL-PTD, TET2, c-CBL, KIT, and other novel AML-associated genes in pediatric AML.
    XII. To correlate the expression of CD74 antigen as well as PSMB5 gene expression and mutation with response to bortezomib.
    XIII. To evaluate the changes in protein expression and unfolded protein response (UPR) in patients with AML. XIV. To determine the expression level of wild-type FLT3, and correlate with outcome and in vitro sensitivity to FLT3 inhibition.
    XV. To obtain sorafenib and metabolite steady state pharmacokinetics and pharmacokinetic- pharmacodynamic data in subjects with FLT3/ITD receiving sorafenib.
    XVI. To collect biology specimens at diagnosis, treatment time points, and relapse for future biology studies.
    OUTLINE: This is a multicenter, dose-escalation study of sorafenib tosylate and an open-label randomized study. Patients are stratified according to disease risk (low vs high). Patients are randomized to 1 of 2 treatment arms or offered treatment on a third arm.
    INDUCTION I:
    ARM A: Patients receive cytarabine intrathecally (IT) on day 1 and ADE chemotherapy comprising cytarabine IV over 15-30 minutes on days 1-10; daunorubicin IV over 1-15 minutes on days 1, 3, and 5; and etoposide IV over 1-2 hours on days 1-5.
    ARM B: Patients receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A. Patients also receive bortezomib IV on days 1, 4, and 8.
    ARM C (high-risk [HR] FLT3/ITD+ disease): Patients receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A and sorafenib tosylate orally (PO) on days 11-28.
    INDUCTION II: Patients without HR FLT3/ITD+ disease begin Induction II administration on day 29.
    ARM A (low-risk [LR] patients): Patients receive cytarabine IT and ADE chemotherapy as in Induction I Arm A.
    ARM A (HR patients): Patients receive cytarabine IT on day 1 and MA chemotherapy comprising high-dose cytarabine IV over 1-3 hours on days 1- 4, and mitoxantrone IV over 15-30 minutes on days 3-6.
    ARM B (LR patients): Patients receive cytarabine IT, ADE chemotherapy, and bortezomib as in Induction I Arm B.
    ARM B (HR patients): Patients receive cytarabine IT and MA chemotherapy as in Induction II, Arm A (HR patients) and bortezomib IV on days 1, 4, and 8.
    ARM C (patients with HR FLT3/ITD+ disease, cohorts 1 and 2): Patients receive cytarabine IT on day 1, cytarabine IV over 15-30 minutes on days 1-8, daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and etoposide IV over 1-2 hours on days 1-5, and sorafenib tosylate PO on days 1-28.
    Patients who achieve complete remission (CR) proceed to Intensification I (beginning on day 29). Patients with refractory disease are off protocol therapy.
    INTENSIFICATION I:
    ARM A: Patients receive cytarabine IT on day 1 and AE chemotherapy comprising high-dose cytarabine IV over 1-3 hours, and etoposide IV over 1- 2 hours on days 1-5.
    ARM B: Patients receive cytarabine IT and AE chemotherapy in Intensification II, Arm A, and bortezomib IV on days 1, 4, and 8.
    ARM C (cohorts 1 and 2): Patients receive cytarabine IT and AE chemotherapy in Intensification II, Arm A, and sorafenib tosylate PO on daily on days 1-28.
    Patients who achieve CR proceed to Intensification II or stem cell transplantation (SCT) beginning on day 29. Patients with refractory disease are off protocol therapy.
    INTENSIFICATION II:
    ARM A (LR): Patients receive cytarabine IT on day 1 and MA chemotherapy as in Induction II, Arm A (HR patients).
    ARM B (LR): Patients receive cytarabine IT on day 1, MA chemotherapy as in Induction II, Arm A (HR patients), and bortezomib IV on days 1, 4, and 8.
    ARMS A AND B (HR and no donor for SCT): Patients receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, and 9 and asparaginase intramuscularly (IM) on days 2 and 9.
    ARM C (HR cohorts 1 and 2): Patients receive cytarabine IT on day 1, MA chemotherapy as in Induction II, Arm A (HR patients), and sorafenib tosylate PO on days 1-28.
    STEM CELL TRANPLANTATION (SCT) (HR patients with matched family [MFD] or unrelated donor):
    CONDITIONING REGIMEN: Patients receive fludarabine IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2.
    TRANSPLANTATION: Patients undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan.
    GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO beginning on day -2 and continuing until day 98 (matched sibling donor) or day 180 (with taper) (other related/unrelated donors or cord blood) and methotrexate IV on days 1, 3, and 6 (matched sibling/cord blood donors) or days 1, 3, 6, and 11 (other related/unrelated donors). Patients with unrelated donors also receive antithymocyte globulin IV over 6-8 hours on days -3 to -1.
    Blood, bone marrow, and tissue samples are collected at baseline and periodically during study for mutation and translocation analysis, cytogenetic/FISH analysis, gene and protein expression, and other studies. Some patients (aged 2 to 18 years) and/or parents may complete questionnaires about health-related quality of life (Pediatric Quality of Life (PedsQL) 4.0 Generic Core Scale, the PedsQL 3.0 Acute Cancer Module, and the PedsQL Multidimensional Fatigue Scale) and parental stress (Pediatric Inventory for Parents (PIP) scale) at baseline and periodically during the study and follow-up.
    After completion of study therapy, patients are followed up monthly for 6 months, every 2 months for 6 months, every 3 months for 1 year, every 6 months for 1 year, and then yearly for up to 8 years.

    TRIAL NUMBER: ACCL0933

    Title: A RANDOMIZED OPEN-LABEL TRIAL OF CASPOFUNGIN VERSUS FLUCONAZOLE TO PREVENT INVASIVE FUNGAL INFECTIONS IN CHILDREN UNDERGOING CHEMOTHERAPY FOR ACUTE MYELOID LEUKEMIA (AML)

    Purpose: OBJECTIVES:
    Primary
    ?To determine if prophylaxis with caspofungin administered during periods of neutropenia following chemotherapy for acute myeloid leukemia (AML) is associated with a lower incidence of proven or probable invasive fungal infections (IFI) compared with fluconazole. Secondary
    ?To determine if prophylaxis with caspofungin will result in a lower incidence of proven or probable cases of invasive aspergillosis (IA) compared with fluconazole. ?To determine if prophylaxis with caspofungin will result in improved survival compared to fluconazole. ?To determine if prophylaxis with caspofungin will result in less empiric antifungal therapy compared to fluconazole. ?To determine the sensitivity, specificity, and positive and negative predictive value of biweekly galactomannan (GM) and beta-D glucan testing in diagnosing IFI. ?To test the association between single nucleotide polymorphisms (SNPs) in genes involved in innate immunity and proven or probable IFI. ?To develop predictive models of IFI using SNP in genes involved in immunity and clinical covariates. OUTLINE: This is a multicenter study. Patients are stratified according to disease (de novo acute myeloid leukemia vs all other patients). Patients are randomized to 1 of 2 treatment arms.
    ?Arm I: Patients receive caspofungin acetate IV over 1 hour once daily (QD) beginning within 24 hours following completion of each course of chemotherapy and continuing until ANC > 100/?L (recommended > 200/?L for 2 consecutive days) or the next chemotherapy course begins. ?Arm II: Patients receive fluconazole IV over 2 hours or orally (PO) QD beginning within 24 hours following completion of each course of chemotherapy and continuing until ANC > 100/?L (recommended > 200/?L for 2 consecutive days) or the next chemotherapy course begins. In both arms, treatment continues in the absence of invasive fungal infections or disease progression.
    Blood samples may be collected twice weekly for antifungal antigen assays and at the end of course 1 for single nucleotide polymorphism analysis.
    After completion of study treatment, patients are followed up periodically for 2 years.

    TRIAL NUMBER: ACCL1333

    Title: A Phase III Randomized, Open Label, Multi-center Study of the Safety and Efficacy of Apixaban for Thromboembolism Prevention versus No Systemic Anticoagulant Prophylaxis during Induction Chemotherapy in Children with Newly-Diagnosed Acute Lymphoblastic Leukemia (ALL) or Lymphoma (T or B cell) Treated with Pegylated Asparaginase; Protocol CV185155

    Purpose: Study Objectives: Primary Objectives: ? To compare the effect of prophylactic oral or enteric apixaban versus no administration of systemic prophylactic anticoagulant during induction chemotherapy, on the composite endpoint of adjudicated non-fatal deep vein thrombosis (DVT, including symptomatic and asymptomatic), pulmonary embolism (PE), and cerebral venous sinus thrombosis (CVST); and venous thromboembolism (VTE)-related-death during 25-28 days of open-label treatment in pediatric subjects (1 to < 18 years) with newly diagnosed ALL or lymphoma (T or B cell), a functioning central venous access device (CVAD) and receiving PEG L-asparaginase during chemotherapy induction. ? To assess the effect of prophylactic oral or enteric apixaban versus no administration of systemic prophylactic anticoagulant during induction chemotherapy, on adjudicated major bleeding events during 25 - 28 days of open-label treatment in pediatric subjects (1 to < 18 years) with newly diagnosed ALL or lymphoma (T or B cell), a functioning CVAD and receiving PEG L-asparaginase during chemotherapy induction. Secondary Objectives: ? To assess the effect of prophylactic oral or enteric apixaban versus no administration of systemic prophylactic anticoagulant during induction chemotherapy, on single adjudicated endpoints of non-fatal DVT (including symptomatic and asymptomatic), PE, and CVST; and VTE-related-death during 25 - 28 days of open-label treatment in pediatric subjects (1 to < 18 years) with newly diagnosed ALL or lymphoma (T or B cell), a functioning CVAD and receiving PEG L-asparaginase during chemotherapy induction. ? To assess the effect of prophylactic oral or enteric apixaban versus no administration of systemic prophylactic anticoagulant during induction chemotherapy, on the composite endpoint of adjudicated major and clinically relevant non-major bleeding (CRNMB) events during 25 - 28 days of open-label treatment in pediatric subjects (1 to < 18 years) with newly diagnosed acute ALL or lymphoma (T or B cell), a functioning CVAD and receiving PEG L-asparaginase during chemotherapy induction. Other Objectives: ? To assess the effect of prophylactic oral or enteric apixaban versus no administration of systemic prophylactic anticoagulant during induction chemotherapy, on single adjudicated endpoints of all cause death; arterial thromboembolic events including paradoxical embolism and stroke and CVAD-related infection events during 25 - 28 days of open-label treatment in pediatric subjects (1 to < 18 years) with newly diagnosed ALL or lymphoma (T or B cell), a functioning CVAD and receiving PEG L-asparaginase during chemotherapy induction. ? To assess the effect of prophylactic oral or enteric apixaban versus no administration of systemic prophylactic anticoagulant during induction chemotherapy, on single adjudicated endpoints of CRNMB and minor bleeding events during 25 - 28 days of open-label treatment in pediatric subjects (1 to < 18 years) with newly diagnosed ALL or lymphoma (T or B cell), a functioning CVAD and receiving PEG L-asparaginase during chemotherapy induction. ? To assess the effect of prophylactic oral or enteric apixaban versus no administration of systemic prophylactic anticoagulant during induction chemotherapy, on single endpoints of number of catheter replacements needed during the study; events of CVAD dysfunction with improvement after thrombolytic therapy; and number of platelet transfusions during 25 - 28 days of open-label treatment in pediatric subjects (1 to < 18 years) with newly diagnosed ALL or lymphoma (T or B cell), a functioning CVAD and receiving PEG L-asparaginase during chemotherapy induction. ? To assess the pharmacokinetics of oral or enteric apixaban in pediatric subjects receiving induction chemotherapy for ALL or lymphoma (T or B cell), using a population pharmacokinetic (PPK) approach. ? To characterize the relationship between apixaban plasma concentration and anti-FXa activity in pediatric subjects receiving induction chemotherapy for ALL or lymphoma (T or B cell). ? To explore the exposure-response relationship between apixaban exposure and safety and efficacy endpoints in pediatric subjects with newly diagnosed ALL or lymphoma (T or B cell).

    TRIAL NUMBER: AHEP0731

    Title: TREATMENT OF CHILDREN WITH ALL STAGES OF HEPATOBLASTOMA

    Purpose: PRIMARY OBJECTIVES:
    I. To estimate the event-free survival (EFS) in pediatric patients with stage I (non-PFH, non-SCU) and stage II (non- SCU) hepatoblastoma treated with surgical resection followed by 2 courses of cisplatin, fluorouracil, and vincristine (C5V).
    II. To determine the feasibility and toxicity of adding doxorubicin hydrochloride to the chemotherapy regimen of C5V for pediatric patients with intermediate-risk hepatoblastoma.
    III. To estimate the response rate to vincristine and irinotecan hydrochloride in previously untreated pediatric patients with high-risk, metastatic hepatoblastoma.
    IV. To determine whether timely (between diagnosis and end of second course of chemotherapy) consultation with a treatment center with surgical expertise in major pediatric liver resection and transplant can be achieved in 70% of patients with potentially unresectable hepatoblastoma.
    V. To foster the collection of tumor tissue and biologic samples to facilitate translational research and to provide data that may aid in risk-adapted approaches for subsequent clinical trials.
    SECONDARY OBJECTIVES:
    I. To estimate the EFS of patients with stage I PFH treated with surgery alone. II. To determine whether liver transplantation (OLT) can be accomplished after successful referral and completion of 4 courses of initial chemotherapy.
    III. To estimate the 2-year EFS for patients once identified as candidates for possible OLT, the 2-year EFS for patients referred to a transplant center that are resected without OLT, and the 2-year EFS for patients referred to a transplant center who receive OLT.
    IV. To register pediatric patients with hepatoblastoma who receive OLT with PLUTO (Pediatric Liver Unresectable Tumor Observatory), an international cooperative registry for pediatric patients transplanted for liver tumors.
    V. To determine if PRETEXT grouping can predict tumor resectability. VI. To monitor the concordance between institutional assessment of PRETEXT grouping and PRETEXT grouping as performed by expert panel review.
    VII. To estimate the proportion of stage IV patients who have surgical resection of metastatic pulmonary lesions.
    VIII. To determine the proportion and estimate the EFS of patients with potentially poor prognostic factors including AFP < 100 ng/mL at diagnosis, microscopic positive surgical margins, surgical complications, multifocal tumors, microscopic vascular invasion, macrotrabecular histologic subtype, and SCU histologic subtype.
    OUTLINE: This is a multicenter study. Patients are stratified according to risk (very low vs low vs intermediate vs high). Patients are assigned to 1 of 4 treatment groups according to risk group.
    VERY LOW-RISK GROUP: Patients undergo surgery and receive no further treatment.
    LOW-RISK GROUP: (regimen T) Patients undergo surgery and then receive adjuvant cisplatin IV over 6 hours on day 1, fluorouracil IV on day 2, and vincristine sulfate IV on days 2, 9, and 16. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
    INTERMEDIATE-RISK GROUP: (regimen F) Patients receive C5VD chemotherapy comprising cisplatin IV over 6 hours on day 1, fluorouracil IV on day 2, vincristine sulfate IV on days 2, 9, and 16, and doxorubicin hydrochloride IV over 15 minutes on days 1-2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo surgical resection after course 2 OR surgical resection or liver transplantation after course 4 of C5VD.
    HIGH-RISK GROUP: (regimen W) Patients receive up front VI chemotherapy comprising vincristine sulfate IV on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1- 5. Treatment with VI repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 1 courses of VI in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity. Patients undergo tumor resection or liver transplantation after course 4 of C5VD followed by 2 courses of adjuvant C5VD.
    After completion of study therapy, patients who receive chemotherapy are followed up periodically for at least 4 years.

    TRIAL NUMBER: AHEP1531

    Title: Pediatric Hepatic Malignancy International Therapeutic Trial (PHITT)

    Purpose: Primary Outcome Measures : Event-free survival (EFS) [ Time Frame: From date of randomization until progression of existing disease or occurrence of disease at new sites, death from any cause prior to disease progression, or diagnosis of a second malignant neoplasm, assessed up to 5 years ] Descriptive analysis for each non-randomized and randomized question (by treatment arm and overall) will include: the number (and proportion) of each failure event and in total, survival curves will be estimated by the method of Kaplan-Meier, EFS estimates at 3 and 5 years with 95% confidence intervals (CI), median EFS with CI will be reported if appropriate. A Cox proportional hazards model with EFS as an outcome measure and treatment and stratification factors as covariates will be constructed. This model will be used in the context of a Bayesian analysis and a log Hazard Ratio (HR) will be derived. Bayesian Normal-Normal conjugate analysis of the data will be used to compare treatments. The analysis will use non-informative prior to represent no information about prior beliefs regarding relative treatment difference.
    Response in hepatocellular carcinoma (HCC), defined as complete (CR) or partial (PR) response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria [ Time Frame: Up to 5 years ] The main analysis will be based on a log-binomial model for a Bernoulli response variable. This model will be used in the context of a Bayesian analysis. A non-informative null centered proper prior distributions for the parameters will be used. Response rate (RR) and 95% credible interval (CrI) will be presented. Posterior probabilities for the pre-specified values of interest will be provided. Additionally, the posterior probabilities of RR being larger than 0.7, 0.8, 0.9, 1, 1.1, 1.2 and 1.3 will be also provided.

    Secondary Outcome Measures : Failure free survival [ Time Frame: From date of randomization until the date of first documented progression, date of death from any cause, diagnosis of a second malignant neoplasm or failure to go to resection, whichever came first, assessed up to 5 years ] Descriptive analysis for each non-randomized and randomized question (by treatment arm and overall) will include: the number (and proportion) of each failure event and in total, survival curves will be estimated by the method of Kaplan-Meier. Bayesian Normal-Normal conjugate analysis of the data will be used to compare treatments. The analysis will use non-informative prior to represent no information about prior beliefs regarding relative treatment difference.
    Overall survival [ Time Frame: From date of randomization (or registration for non-randomized patients) until the date of death from any cause, assessed up to 5 years ] Incidence of adverse events [ Time Frame: Up to 5 years ] Will be categorized and graded using Common Terminology Criteria for Adverse Events (CTCAE).
    Chemotherapy-related cardiac, nephro- and oto-toxicity [ Time Frame: Up to 5 years ] Will be recorded in relation to each cycle of treatment and will be categorized and graded using Common Terminology Criteria for Adverse Events.
    Hearing loss measured according to the SIOP Boston Scale for oto-toxicity [ Time Frame: Up to 5 years ] Descriptive analysis for each non-randomized and randomized question (by treatment arm and overall) will include: the number (and proportion) of patients at each the SIOP Boston Scale for oto-toxicity category (i.e. grade 0 to grade 4) and the number (and proportion) of patients who are not assessable for this outcome, (i.e. because of early stopping of treatment, additional treatments to protocol treatment, progression prior to the response assessment or death). The number (and proportion) of patients experiencing any grade hearing loss. Grades 1 to grade 4 will be combined in this analysis. The above will be presented for each assessment time point (EOT and at least 1 year and 2 years of follow up).
    Best response defined as compete response (CR) or partial response (PR) based on radiological response (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) and AFP decline [ Time Frame: Up to 5 years ] Descriptive analysis for each non-randomized and randomized question (by treatment arm and overall) will include: best response will be calculated by taking best RECIST category (i.e. CR, PR, stable disease [SD], progressive disease [PD]) for each patient. CR and PR patients will then be grouped into responders. The number (and proportion) of patients at each best response RECIST category (i.e. CR, PR, SD, PD) and the number (and proportion) of patients who are not assessable for response, e.g. because of early stopping of treatment, progression prior to the response assessment or death. The number (and proportion) of responders (CR and PR) and non-responders.
    Surgical resectability defined as complete resection, partial resection or transplant following randomization (or enrollment for non-randomized patients) [ Time Frame: Up to 5 years ] Descriptive analysis for each non-randomized and randomized question (by treatment arm and overall) will include: The number (and proportion) of patients undergoing complete resection, partial resection or transplant. Time to complete resection, partial resection or transplant following randomization (or enrollment for non-randomized patients) will be analyzed using the Kaplan-Meier method.
    Adherence to surgical guidelines defined as the local clinician?s surgical decision to resect or not compared to the current SIOPEL surgical guidelines [ Time Frame: Up to 5 years ] Descriptive analysis for each non-randomized and randomized question (by treatment arm and overall) will include: The number (and proportion) of patients at each combination of SIOPEL surgical guideline (to resect or not) and local clinician?s surgical decision. The degree of agreement will be measured by Cohen?s kappa with CI.

    TRIAL NUMBER: AALL1731

    Title: A Phase 3 Trial Investigating Blinatumomab (IND# 117467, NSC# 765986) in Combination with Chemotherapy in Patients with Newly Diagnosed Standard Risk or Down syndrome B-Lymphoblastic Leukemia (B-ALL) and the Treatment of Patients with Localized B-Lymphoblastic Lymphoma (B-LLy)

    Purpose:

    Primary Outcome Measures :
    1. Post-Consolidation disease free survival (DFS) with addition of 2 cycle of blinatumomab in patients with standard risk (SR) B-lymphoblastic leukemia (B-ALL) and higher risk features, and patients with standard risk average (SR-Avg) B-ALL [ Time Frame: 5 years ]
      Efficacy design and standard survival analysis methods used to detect improvement in post-Consolidation DFS due to the addition of 2 cycles of blinatumomab to standard therapy in patients with SR B-ALL and higher risk features, and patients with SR-Avg B-ALL who are negative for minimal residual disease (MRD) by flow cytometry but have detectable or indeterminate MRD as measured by high-throughput sequencing (HTS) at end of induction (EOI), and patients with double trisomy of chromosomes 4 and 10 (DT) with MRD (flow) 0.01% - <0.1%.

    2. DFS in boys in the SR-favorable subset of SR B-ALL [ Time Frame: 5 years ]
      Time from end of consolidation to first event (relapse, second malignant neoplasm, remission, death) or censored at date of last contact for those who are disease-free.


    Secondary Outcome Measures :
    1. DFS for patients with SR-Avg B-ALL who are negative for MRD measured by flow cytometry and HTS at EOI when treated with standard chemotherapy with a treatment duration of 2 years from the start of interim maintenance (IM)1, regardless of sex [ Time Frame: 5 years ]
      Time from end of consolidation to first event (relapse, second malignant neoplasm, remission, death) or censored at date of last contact for those who are disease-free.

    2. DFS for patients with standard-risk favorable (SR-Fav) B-ALL [ Time Frame: 5 years ]
      Time from end of consolidation to first event (relapse, second malignant neoplasm, remission, death) or censored at date of last contact for those who are disease-free.

    3. Treatment-related mortality in Down syndrome high risk (DS-high) patients after replacement of intensive elements of standard chemotherapy (omission of anthracyclines in induction, omission of the second month of DI) with 3 cycles of blinatumomab [ Time Frame: 5 years ]
    4. DFS of DS-High B-ALL patients when intensive elements of chemotherapy are replaced with 3 cycles of blinatumomab [ Time Frame: 5 years ]
      Time from end of consolidation to first event (relapse, second malignant neoplasm, remission, death) or censored at date of last contact for those who are disease-free.

    5. DFS of patients with localized B-lymphoblastic lymphoma receiving standard risk acute lymphoblastic leukemia therapy [ Time Frame: 5 years ]
      Time from end of consolidation to first event (relapse, second malignant neoplasm, remission, death) or censored at date of last contact for those who are disease-free.

    6. Neurocognitive functioning [ Time Frame: Baseline to 2 years after IM1 ]
      Compare the change in neurocognitive functioning, as measured by the CogState Cognitive Composite, from baseline to end-of-therapy among patients with ALL ages 4-< 10 years at the time of diagnosis between children from poor families (defined as presence of household material hardship (HMH), including either food, housing or energy insecurity) and non-poor families (absence of HMH).

    7. Caregiver burden and patient/proxy-reported symptoms among those enrolled in HMH [ Time Frame: Baseline to 2 years after IM1 ]
      Compare the demands and work limitations on caregivers of children with ALL receiving chemotherapy versus chemotherapy with the addition of blinatumomab and to compare the change in the demands and work limitations over time, measured by the Care of My Child with Cancer questionnaire and the Caregiver Work Limitations questionnaire during post-Induction therapy. Patient/proxy reported symptoms measured by Memorial Symptom Assessment Scale.


    Other Outcome Measures:
    1. Adaptive and innate immune functions and host genetic factors associated with severe infectious complications in children with DS B-ALL [ Time Frame: 5 years ]
      FlowSom high resolution clustering approach to identify cellular subsets and/or activation states (endophenotypes) that distinguish cases from controls. Conduct a genome-wide assessment using a case-control approach comparing those who develop grade 4-5 microbiologically documented infections (cases) compared to those who do not (controls).

    2. Neurocognitive, functional, and quality of life outcomes in patients with DS and ALL [ Time Frame: 5 years ]
      Measured by caregiver (parent/legal guardian) questionnaires.

    3. Prevalence of minimal marrow disease (MMD) in B-LLy [ Time Frame: 5 years ]
      Correlate MMD at diagnosis with outcome in patients with B-LLy.

    TRIAL NUMBER: ABTR01B1

    Title: A CHILDREN'S ONCOLOGY GROUP PROTOCOL FOR COLLECTING AND BANKING PEDIATRIC RESEARCH SPECIMENS

    Purpose:

    TRIAL NUMBER: ACCL0934

    Title: A RANDOMIZED TRIAL OF LEVOFLOXACIN TO PREVENT BACTEREMIA IN CHILDREN BEING TREATED FOR ACUTE LEUKEMIA (AL) OR UNDERGOING HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT)

    Purpose: OBJECTIVES:
    Primary
    ?To determine whether levofloxacin given prophylactically during periods of neutropenia to patients being treated with chemotherapy for acute leukemia (AL) or undergoing hematopoietic stem cell transplantation (HSCT) will decrease the incidence of bacteremia. Secondary
    ?To determine the effect of prophylactic levofloxacin on resistance patterns of bacterial isolates from all sterile site cultures, and the evolution of antimicrobial resistance from peri-rectal swab isolates of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Streptococcus mitis. ?To determine the effect of levofloxacin prophylaxis on total number of days of antibiotic administration (prophylactic, empiric, and treatment) in children undergoing therapy for AL or HSCT. ?To determine whether levofloxacin prophylaxis reduces the incidence of fever with neutropenia, severe infection, and death from bacterial infection. ?To assess the safety of levofloxacin prophylaxis, with specific attention to musculoskeletal disorders including tendinopathy and tendon rupture. ?To assess the impact of prophylactic levofloxacin on the incidence of Clostridium difficile-associated diarrhea (CDAD), and the incidence of microbiologically documented invasive fungal infections (IFI). OUTLINE: This is a multicenter study. Patients are stratified according to diagnosis (de novo acute myeloid leukemia [AML] vs secondary AML vs relapsed AML vs relapsed acute lymphoblastic leukemia [ALL]), and therapy (undergoing autologous HSCT vs undergoing allogeneic HSCT). Patients are randomized to 1 of 2 treatment groups.
    ?Arm I: Patients receive levofloxacin orally (PO) or IV over 60-90 minutes once or twice daily beginning on day 1 during 2 consecutive courses of chemotherapy or beginning on day -2 during hematopoietic stem cell transplantation (HSCT) and continuing until blood counts recover. ?Arm II: Patients receive established standard of care and receive chemotherapy or HSCT as patients in arm 1. Musculoskeletal assessment is conducted at baseline and at 2 and 12 months.
    Patients may undergo perirectal or stool swab collection for ancillary studies.
    After completion of study therapy, patients are followed up for 1 year.

    TRIAL NUMBER: ACCL1034

    Title: Impact of Cleansing with Chlorhexidine Gluconate (CHG) on Reducing Central Line Associated Bloodstream Infection (CLABSI) and Acquisition of Multi-drug Resistant Organisms (MDRO) in Children with Cancer or Those Receiving Allogeneic Hematopoietic Cell Transplantation (HCT): A Limited Phase III Study

    Purpose: PRIMARY OBJECTIVES:
    I. To determine whether chlorhexidine gluconate (CHG) cleansing decreases central line associated bloodstream infection (CLABSI) in children with cancer or those receiving an allogeneic hematopoietic cell transplantation (HCT).
    SECONDARY OBJECTIVES:
    I. To determine whether CHG cleansing decreases acquisition of multi-drug resistant organisms (MDRO: vancomycin resistant enterococci [VRE], methicillin resistant Staphylococcus aureus [MRSA], etc.) in children with cancer or those receiving allogeneic HCT.
    II. To determine whether CHG cleansing in children with cancer or those receiving allogeneic HCT is associated with cutaneous bacterial isolates with reduced susceptibility to CHG.
    III. To determine whether CHG cleansing decreases positive blood cultures in children with cancer or those receiving allogeneic HCT.
    OUTLINE: Patients are randomized to 1 of 2 arms.
    ARM I: Patients receive CHG cleansing with topical skin wipes once daily (QD) for 90 days.
    ARM II: Patients receive control cleansing with topical skin wipes QD for 90 days.

    TRIAL NUMBER: ACCL1131

    Title: A Phase III Open-Label Trial of Caspofungin vs. Azole Prophylaxis for Patients at High-Risk for Invasive Fungal Infections (IFI) Following Allogeneic Hematopoietic Cell Transplantation (HCT)

    Purpose: PRIMARY OBJECTIVES:
    I. To determine if caspofungin (caspofungin acetate) is associated with a lower incidence of proven/probable invasive fungal infections (IFI) during the first 42 days following allogeneic hematopoietic cell transplantation (HCT) at high-risk for IFI compared with azole (fluconazole or voriconazole) prophylaxis.
    SECONDARY OBJECTIVES:
    I. To determine if caspofungin is associated with a lower incidence of proven/probable IFI during the first 100 days following high-risk allogeneic HCT compared with azole (fluconazole or voriconazole) prophylaxis. (Exploratory) II. To determine if caspofungin is associated with a lower incidence of proven/probable IFI during the first 42 and 100 days following high-risk allogeneic HCT compared with fluconazole prophylaxis. (Exploratory) III. To determine if caspofungin is associated with a lower incidence of proven/probable IFI during the first 42 and 100 days following high-risk allogeneic HCT compared with voriconazole prophylaxis. (Exploratory) IV. To determine if caspofungin is associated with a superior fungal-free survival (FFS) (time to death or proven/probable IFI) at 42 and 100 days following high-risk allogeneic HCT compared with azole prophylaxis. (Exploratory) V. To describe the effect that caspofungin and azoles have on the incidence and severity of acute graft-versus-host disease (GVHD). (Exploratory) VI. To create a deoxyribonucleic acid (DNA) specimen bank in anticipation of the development of biology correlative studies exploring the relationship between IFI and single nucleotide polymorphisms (SNPs) of genes involved in immunity. (Exploratory)
    OUTLINE: Patients are randomized to 1 of 2 treatment arms.
    ARM I: Patients receive caspofungin acetate intravenously (IV) over 1 hour once daily (QD) beginning within 24 hours of allogeneic hematopoietic stem cell transplantation (HSCT) (day -1 or 0) and continuing until day 42 in the absence of invasive fungal infections or disease progression.
    ARM II: Patients receive fluconazole IV over 1-2 hours QD or orally (PO) QD; or voriconazole IV over 1-2 hours QD or PO twice daily (BID) beginning within 24 hours of allogeneic HSCT (day -1 or 0) and continuing until day 42 in the absence of invasive fungal infections or disease progression.
    After completion of study treatment, patients are followed up until day 100.

    TRIAL NUMBER: ACCL1633

    Title: COG ACCL1633, The Effectiveness of Lactobacillus plantarum in Preventing Acute Graft-versus-Host Disease (GvHD) in Children undergoing Alternative Hematopoietic Progenitor Cell Transplantation (HCT)

    Purpose: Graft vs Host Disease affect up to 45% of pediatric patients that receive allogeneic hematopietic cel transplantation. There is a need for better prevention and therapy for aGVHD, has cause 20% of deaths. This study is to determine the efficacy of orally-administered LBP in preventing GI aGVHD, hoping it will decrease the severity.

    TRIAL NUMBER: ACCRN07

    Title: PROTOCOL FOR THE ENROLLMENT ON THE OFFICIAL COG REGISTRY, THE CHILDHOOD CANCER RESEARCH NETWORK (CCRN)

    Purpose: Institutional membership in the Children's Oncology Group (COG) requires registration of all pediatric cancer patients seen at their site. This registration process includes all patients. It has previously been shown that the two major pediatric cooperative groups (CCG and POG), which currently comprise COG, identify approximately 90% of children diagnosed with cancer under the age of 15 years in the U.S (1) The cooperative group resource provides the basis to build a childhood cancer network to facilitate research. In order to maximize the resource that a network would provide, it is necessary to have identifying information on a large proportion of the cases included within the network. Moreover, the resource would be further enhanced if informed consent from parents/patients was obtained to allow future contact regarding possible participation in non-therapeutic and prevention research. This protocol is designed to facilitate the systematic entry of pediatric and adolescent patients diagnosed with cancer into a Childhood Cancer Research Network (CCRN). There are two levels of entry in the CCRN: 1) Entry in the CCRN with consent but without permission for future contact. The data collected for these registry entries will include Protected Health Information (PHI) and will therefore be uniquely identifying (see Section 5.0 for specific data to be collected). 2) Entry in the CCRN with consent including permission for future contact. The data collected for these registry entries will include PHI and will therefore be uniquely identifying (see Section 5.0 for specific data to be collected). Additionally, patient and parent contact information will be collected to facilitate future contact.

    TRIAL NUMBER: ALTE05N1

    Title: Umbrella Long-Term Follow-Up Protocol

    Purpose: OBJECTIVES:
    ?To develop a mechanism for tracking and retaining patients enrolled on COG protocols. ?To maintain regular, lifetime contact with patients in order to obtain current identification and contact information, and self/parent-reported health status. ?To locate patients who are lost-to-follow-up for COG (or Legacy Group) protocols targeted for follow-up by the Long-Term Follow-Up Center (LTFC). ?To provide current patient contact information and self/parent-reported health status updates to the COG Statistics and Data Center (SDC) and to each patient's COG institution. ?To facilitate collection of protocol-specific outcome data through collaboration with the COG Late Effects Committee, the SDC, and the member institutions. ?To collect cumulative therapeutic exposure data (via therapeutic summaries completed online by treating institutions) on patients completing active therapy. OUTLINE: This is an umbrella protocol for all long-term follow-up at COG institutions. Approximately 6 months after completion of therapy patients receive a mailed packet introducing the Long-Term Follow-Up Center (LTFC) and containing information related to their individualized, protocol-specific follow-up guidelines. Patients are asked to complete a patient response form, verify information provided in packet, update contact information, and complete a Health Status Update Form. The Health Status Update Form is a brief document including questions about current health status, disease status, and cancer therapy received since the last mailing. Patients receive protocol-specific automatic reminders, and may respond by use of postage prepaid envelopes, email, or 24-hour toll-free telephone.

    TRIAL NUMBER: ALTE07C1

    Title: NEUROPSYCHOLOGICAL, SOCIAL, EMOTIONAL, AND BEHAVIORAL OUTCOMES IN CHILDREN WITH CANCER

    Purpose: OBJECTIVES:
    I. To utilize a standardized battery of age-appropriate neuropsychological and behavioral tests in conjunction with Children's Oncology Group (COG) Phase III clinical trials to evaluate cognitive, social, emotional, and behavioral functioning over time.
    II. To institute procedures to ensure a consistent, streamlined, and efficient administration of the neuropsychological/behavioral tests in a cooperative group setting in order to maximize compliance with a standardized assessment battery conducted at 3 standardized timepoints.
    OUTLINE:
    Parent and child participants complete the COG Standard Neuropsychological and Behavioral Battery testing at 9, 30, and 60 months post-diagnosis in a 1-hour session conducted by a neuropsychologist or psychologist. The Battery consists of tests of intelligence, processing speed/attention, memory, language preference, general developmental progress, attention and behavior/social/emotional function, executive function, adoptive function, and quality of life. Additionally, parents complete a parent-report questionnaire to gather information about patient's function in terms of attention, memory, executive abilities, and behavioral, social, and emotional adaption.

    TRIAL NUMBER: APEC1621A

    Title: Pediatric MATCH: Trk Inhibitor LOXO-101 in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions

    Purpose: This phase II trial studies Trk inhibitor LOXO-101 in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with NTRK fusions that have spread to other places in the body and have come back or do not respond to treatment. Trk inhibitor LOXO-101 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth

    TRIAL NUMBER: APEC1621B

    Title: Pediatric MATCH: Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations

    Purpose: This phase II trial studies how well erdafitinib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders that have spread to other places in the body and have come back or do not respond to treatment with FGFR mutations. Erdafitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621C

    Title: Pediatric MATCH: Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations

    Purpose: This phase II trial studies how well tazemetostat works in treating patients with solid tumors, non-hodgkin lymphoma, or histiocytic disorders that have spread to other places in the body and have come back or do not respond to treatment and have EZH2, SMARCB1, or SMARCA4 gene mutations. Tazemetostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621D

    Title: Pediatric MATCH: PI3K/mTOR Inhibitor LY3023414 in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations

    Purpose: This phase II trial studies how well PI3K/mTOR inhibitor LY3023414 works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with TSC or PI3K/MTOR mutations that have spread to other places in the body and have come back or do not respond to treatment. PI3K/mTOR inhibitor LY3023414 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621E

    Title: Pediatric MATCH: Selumetinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating MAPK Pathway Mutations

    Purpose: This phase II trial studies how well selumetinib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with MAPK pathway activation mutations that have spread to other places in the body and have come back or do not respond to treatment. Selumetinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621F

    Title: Pediatric MATCH: Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations

    Purpose: This phase II trial studies how well ensartinib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with ALK or ROS1 genomic alterations that have come back or do not respond to treatment and have spread to other places in the body. Ensartinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621G

    Title: Pediatric MATCH: Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations

    Purpose: This phase II trial studies how well vemurafenib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with BRAF V600 mutations that have spread to other places in the body and have come back or do not respond to treatment. Vemurafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621H

    Title: Pediatric MATCH: Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes

    Purpose: This phase II trial studies how well olaparib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with defects in deoxyribonucleic acid (DNA) damage repair genes that have spread to other places in the body and have come back or do not respond to treatment. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621SC

    Title: Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders

    Purpose: This screening and multi-sub-study phase II trial studies how well treatment that is directed by genetic testing works in pediatric patients with solid tumors, non-Hodgkin lymphomas, or histiocytic disorders that have progressed following at least one line of standard systemic therapy and/or for which no standard treatment exists that has been shown to prolong survival. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic changes or abnormalities (mutations) may benefit more from treatment which targets their tumor's particular genetic mutation, and may help doctors plan better treatment for patients with solid tumors or non-Hodgkin lymphomas.

    TRIAL NUMBER: ARST1321

    Title: Pazopanib Neoadjuvant Trial in Non-Rhabdomyosarcoma Soft Tissue Sarcomas (PAZNTIS): A Phase II/III Randomized Trial of Preoperative Chemoradiation or Preoperative Radiation Plus or Minus Pazopanib (NSC #737754, IND #118613)

    Purpose: PRIMARY OBJECTIVES:
    I. To identify the dose of pazopanib (pazopanib hydrochloride) that is feasible when given in combination with radiation or chemoradiation in pediatric and adult patients newly diagnosed with unresected intermediate- and high-risk non-rhabdomyosarcoma soft tissue sarcomas (NRSTS).
    II. To compare the rates of near complete pathologic response (> 90% necrosis) with the addition of pazopanib to preoperative chemoradiation versus preoperative chemoradiation alone for potentially resectable > 5 cm, grade 3 intermediate to high risk chemotherapy-sensitive NRSTS in the phase II portion of the study for this cohort.
    III. To compare the rates of near complete pathologic response (> 90% necrosis) with the addition of pazopanib to preoperative radiotherapy versus preoperative radiotherapy alone for potentially resectable intermediate to high risk adult and pediatric NRSTS in the phase II portion of the study for this cohort (using a phase II decision rule to go onto the Phase III portion of the study).
    IV. To compare the rates of event-free survival (EFS) with the addition of pazopanib to preoperative radiotherapy versus preoperative radiotherapy alone for localized intermediate to high risk adult and pediatric NRSTS in the phase III portion of the study for this cohort if the phase II decision rule is passed.
    SECONDARY OBJECTIVES:
    I. To estimate the rates of local failure, regional failure, distant metastasis free survival, disease-free survival, and overall survival with the addition of pazopanib to preoperative chemoradiation or preoperative radiation in intermediate to high risk adult and pediatric NRSTS.
    II. To compare the pattern of recurrence (local, regional and distant) between preoperative chemoradiation or radiation with the addition of pazopanib for adult and pediatric NRSTS.
    III. To define the toxicities of ifosfamide and doxorubicin (doxorubicin hydrochloride) chemotherapy and radiation when used in combination with pazopanib in intermediate to high risk adult and pediatric NRSTS.
    IV. To define the toxicities of preoperative radiotherapy when used in combination with pazopanib in intermediate to high risk adult and pediatric NRSTS.
    TERTIARY OBJECTIVES:
    I. To gain insight into the disease biology of childhood and adult NRSTS through analysis of actionable mutations and whole genome sequencing.
    II. To determine if microvessel density and circulating tumor deoxyribonucleic acid (DNA) predict response to pazopanib and outcome.
    III. To determine the effect of pazopanib on doxorubicin exposure in children and adults with NRSTS.
    IV. To evaluate change in fludeoxyglucose F 18 (FDG) positron emission tomography (PET) maximum standard uptake value (SUVmax) from baseline to week 10 or 13 in patients with unresected tumors and to correlate this change with pathologic response and EFS.
    V. To compare the rate of response by standard imaging and pathologic assessment to determine which correlates better with local tumor control, distant tumor control, EFS, and overall survival.
    OUTLINE: This is a dose-escalation study of pazopanib hydrochloride.
    CHEMOTHERAPY COHORT: Patients eligible for chemotherapy cohort are randomized to 1 of 2 treatment regimens.
    REGIMEN A:
    INDUCTION PHASE: Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on weeks 1-12, ifosfamide intravenously (IV) over 2-4 hours on days 1-3 on weeks 1, 4, 7, 10, and doxorubicin hydrochloride IV over 1-15 minutes on days 1-2 on weeks 1 and 4. Patients undergo radiation therapy on weeks 4-10.
    SURGERY: Patients undergo surgery on week 13.
    CONTINUATION PHASE: Patients receive pazopanib hydrochloride PO QD on weeks 16-25, ifosfamide IV over 2-4 hours on days 1-3 on weeks 16 and 19, and doxorubicin hydrochloride IV over 1-15 minutes on days 1-2 on weeks 16, 19, and 22. Patients undergo radiation therapy on weeks 16-25 for a total of 45 Gy.
    REGIMEN B:
    INDUCTION PHASE: Patients receive ifosfamide IV over 2-4 hours on days 1-3 on weeks 1, 4, 7, 10 and doxorubicin hydrochloride IV over 1-15 minutes on days 1-2 on weeks 1 and 4. Patients undergo radiation therapy on weeks 4-10.
    SURGERY: Patients undergo surgery on week 13.
    CONTINUATION PHASE: Patients receive ifosfamide IV over 2-4 hours on days 1-3 on weeks 16 and 19 and doxorubicin hydrochloride IV over 1-15 minutes on days 1-2 on weeks 16, 19, and 22. Patients undergo radiation therapy on weeks 16-25 for a total of 45 Gy.
    NON-CHEMOTHERAPY COHORT: Patients eligible for non-chemotherapy cohort are randomized to 1 of 2 treatment regimens.
    REGIMEN C:
    INDUCTION PHASE: Patients receive pazopanib hydrochloride PO QD on weeks 1-9. Patients undergo radiation therapy on weeks 1-7.
    SURGERY: Patients undergo surgery on week 10.
    CONTINUATION PHASE: Patients receive pazopanib hydrochloride PO QD on weeks 13-25. Patients undergo radiation therapy on weeks 13-16 for a total of 50 Gy.
    REGIMEN D:
    INDUCTION PHASE: Patients undergo radiation therapy on weeks 1-7.
    SURGERY: Patients undergo surgery on week 10.
    CONTINUATION PHASE: Patients undergo radiation therapy on weeks 13-16 for a total of 50 Gy.
    After completion of study treatment, patients are followed up at 6, 12, 18, 24, 30, 36, 48, and 60 months.

    TRIAL NUMBER: D9902

    Title: A COG SOFT TISSUE SARCOMA DIAGNOSIS, BIOLOGY AND BANKING PROTOCOL

    Purpose:

    TRIAL NUMBER: ACNS0821

    Title: Temozolomide with Irinotecan versus Temozolomide, Irinotecan plus Bevacizumab for Recurrent/Refractory Medulloblastoma/CNS PNET of Childhood, A COG Randomized Phase II Screening Trial

    Purpose: PRIMARY OBJECTIVES:
    l. To compare the overall survival (OS) of subjects receiving the combination of temozolomide and irinotecan with that of subjects receiving temozolomide, irinotecan (irinotecan hydrochloride), and bevacizumab for recurrent medulloblastoma (MB)/primitive neuroectodermal tumor (PNET) of childhood.
    SECONDARY OBJECTIVES:
    I. To assess the response rate for each treatment arm amongst patients who are enrolled with measurable disease.
    II. To determine event-free survival (EFS) for each patient compared across regimens.
    OUTLINE: Patients are randomized to 1 of 2 treatment arms.
    ARM I: Patients receive temozolomide orally (PO) and irinotecan hydrochloride IV over 90 minutes on days 1-5.
    ARM II: Patients receive temozolomide PO and irinotecan hydrochloride IV as in arm I and bevacizumab IV over 30-90 minutes on days 1 and 15.
    In both arms, treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
    After completion of study treatment, patients are followed up for 5 years.

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    TRIAL NUMBER: ACNS1422

    Title: A Phase 2 Study of Reduced Therapy for Newly Diagnosed Average-Risk WNT-Driven Medulloblastoma Patients

    Purpose: Primary Outcome Measures: PFS [ Time Frame: From the initiation of protocol treatment to the occurrence of any of the following events: disease progression or disease recurrence or death from any cause, assessed up to 10 years ] PFS along with the confidence intervals will be estimated using the Kaplan-Meier method. PFS will also be reported based on central radiology review.

    Secondary Outcome Measures: Change in neurocognitive function (cognitive, social, emotional and behavioral) according to Children Oncology Group Standard Neuropsychological Battery [ Time Frame: Baseline to up to 60 months post-diagnosis ] Neurocognitive function will be measured at 9, 30 and 60 months post diagnosis and will be compared with the neurocognitive outcomes from an age and gender matched ACNS0331 cohort to the WNT patients treated on ACNS1422. Data for all assessments will be available as standardized t-scores. The change over time for each component of the neuropsychological testing will be estimated using the Generalized Estimating Equation (GEE) approach, with the standardized t-scores as the dependent variable and the assessment times as a covariate. Within the ACNS1422 cohort GEE models will also be used to exp
    DNA methylation profiling as real-time classification of WNT-driven medulloblastoma [ Time Frame: Within 32 days of definitive surgery ] Results will be compared to the results of the molecular screening tests. The sensitivity and specificity comparison between DNA methylation arrays and the standard methods (molecular screening tests for WNT using IHC and CTNNB1 sequencing) will be performed using McNemar's test.

    Other Outcome Measures: DNA methylation profiling of medulloblastoma real-time" predictive classification scheme for the SHH, group 3 and group 4 medulloblastoma subgroups according to the Heidelberg classifier [ Time Frame: Within 32 days of definitive surgery ] The proportion of patients classified into each medulloblastoma subgroup in "real time" will be reported.

    Estimated Enrollment: 45 Study Start Date: October 2016 Estimated Primary Completion Date: May 2025 (Final data collection date for primary outcome measure)

    TRIAL NUMBER: ANBL00B1

    Title: NEUROBLASTOMA BIOLOGY STUDIES

    Purpose:

    TRIAL NUMBER: ANBL1232

    Title: Utilizing Response- and Biology-Based Risk Factors to Guide Therapy in Patients with Non-High-Risk Neuroblastoma; A Groupwide Historically-Controlled Phase III Study

    Purpose: PRIMARY OBJECTIVES:
    I. To eliminate therapy as the initial approach for infants < 12 months of age with small International Neuroblastoma Risk Group (INRG) stage L1 neuroblastoma while maintaining an overall survival (OS) of 99%.
    II. To eliminate therapy as the initial approach for non-high-risk patients < 18 months of age with localized neuroblastoma and favorable biology (histologic and genomic features) while maintaining an OS of 99%.
    III. To achieve a 3-year OS of > 81% for infants < 18 months of age with INRG stage Ms neuroblastoma using objective criteria for early initiation of a response-based treatment algorithm.
    IV. To achieve a 3-year event free survival (EFS) of > 70% for non-high-risk infants < 12 months of age with INRG stage M neuroblastoma and unfavorable biology (histologic and/or genomic features) through the addition of isotretinoin therapy.
    SECONDARY OBJECTIVES:
    I. To describe the time to intervention or tumor progression, type of intervention and site of progression for patients with localized neuroblastoma who experience progression after an initial period of observation.
    II. To characterize the pharmacokinetic profile of the chemotherapeutic agents carboplatin and etoposide in patients with stage Ms disease.
    III. To define the genomic profile of tumors from patients with non-high-risk neuroblastoma both at initial biopsy and at the time of subsequent biopsy or surgical resection.
    IV. To describe the histology of tumor specimens obtained at the time of subsequent biopsy or surgical resection.
    V. To determine the salvage rate (OS) of patients with tumor relapse or disease progression.
    VI. To determine the procedural complication rate (initial biopsy, resection [intraoperative and postoperative], subsequent biopsy) and correlate with the degree of surgical resection.
    VII. To determine the rate of reduction in image defined risk factors (IDRF) in L2 tumors following observation or chemotherapy.
    VIII. To describe bone abnormalities on bilateral tibial radiographs obtained before and after isotretinoin therapy.
    IX. To determine the variability of isotretinoin pharmacokinetics and relationship to pharmacogenomic parameters and determine if these levels and/or genetic variations correlate with EFS or systemic toxicity.
    OUTLINE: Patients are assigned to 1 of 4 treatment groups.
    GROUP A: Patients undergo clinical observation for 96 weeks.
    GROUP B: Patients undergo clinical observation for 3 years in the absence of disease progression. Upon disease progression, patients undergo surgery or receive first-line chemotherapy comprising carboplatin intravenously (IV) over 1 hour on day 1 (courses 1, 2, 4, 6, and 7), etoposide IV over 1 hour on days 1-3 (courses 1, 3, 4, 5, and 7), cyclophosphamide IV over 1 hour on day 1 (courses 2, 3, 5, 6, and 8), and doxorubicin hydrochloride IV over 15 minutes on day 1 (courses 2, 4, 6 and 8). Treatment with chemotherapy repeats every 21 days for 2-8 courses in the absence of disease progression or unacceptable toxicity. Once a partial response (PR) or better is achieved, patients undergo clinical observation for 3 years.
    GROUP C: Patients at high risk for deterioration and a poor outcome immediately receive first-line chemotherapy as in Group B. All other patients undergo clinical observation for 3 years in the absence of disease progression. Upon disease progression, patients receive first-line chemotherapy as in Group B. Once a PR or better is achieved, patients undergo clinical observation for 3 years.
    GROUP D: Patients receive first-line chemotherapy as in Group B. Patients who achieve a complete response (CR) or very good partial response (VGPR) following first-line chemotherapy receive isotretinoin orally (PO) twice daily (BID) on days 1-14. Treatment with isotretinoin repeats every 28 days for 6 courses. Patients then undergo clinical observation for 3 years. Patients who achieve a PR or stable disease (SD) following first-line chemotherapy receive salvage chemotherapy comprising cyclophosphamide IV over 30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment with salvage chemotherapy repeats every 21 days for 2-6 courses. Patients then receive isotretinoin PO BID on days 1-14. Treatment with isotretinoin repeats every 28 days for 6 courses. Patients then undergo clinical observation for 3 years.
    After completion of study treatment, patients are followed up annually for 5 years.

    TRIAL NUMBER: A011202

    Title: A Randomized Phase III Trial Evaluating the Role of Axillary Lymph Node Dissection in Breast Cancer Patients (CT1-3 N1) Who Have Positive Sentinel Lymph Node Disease After Neoadjuvant Chemotherapy

    Purpose: Study Outline: All patients will undergo surgery to identify sentinel lymph node(s). If a lymph node (sentinel or non-sentinel) is determined to be positive on intra-operative pathology the patient will be registered/randomized intra-operatively. Patients who do not have a sentinel lymph node identified will not be registered/randomized to the study. Patients whose sentinel lymph node status is cannot be/is not determined intra- operatively, and have not undergone ALND, but had at least one lymph node (sentinel or non-sentinel) found to be positive on final pathology review will be registered/randomized post-operatively. Patients whose sentinel lymph node status is found to be negative intra-operatively and have not undergone ALND, but had at least one lymph node (sentinel or non-sentinel) found to be positive on final pathology review will be registered/randomized post-operatively. ALND is not to be performed prior to registration/randomization. Patients who are determined to have negative lymph nodes on final pathology will not be registered/randomized, but can be offered participation in another cooperative group trial. The primary and secondary objectives of the study are described below. Please see the "Arms" section for a detailed description of the treatment regimens. Primary Objective: To evaluate whether radiation to the undissected axilla and regional lymph nodes is not inferior to axillary lymph node dissection with radiation to the regional lymph nodes but not to the dissected axilla in terms of invasive breast cancer recurrence-free interval in patients with positive SLN(s) after completion of neoadjuvant chemotherapy Secondary Objectives: To evaluate whether radiation to the undissected axilla and regional lymph nodes is not inferior to axillary lymph node dissection with radiation to the regional lymph nodes but not to the dissected axilla in terms of the incidence of invasive loco-regional recurrences in patients with a positive SLN(s) after completion of neoadjuvant chemotherapy To obtain an estimate of the distribution of residual disease burden scores for each treatment arm To estimate the distribution of overall survival for each treatment arm Patients may receive adjuvant and ancillary therapy as appropriate per the protocol. Adjuvant Therapy: Adjuvant endocrine therapy: Patients with hormone receptor (ER and/or PR) positive disease should receive a minimum of 5 years of standard endocrine therapy (experimental agents/regimens are not permitted). Endocrine therapy should begin following completion of neoadjuvant chemotherapy and surgery, either before, during or after radiation therapy at the discretion of the oncologist. Selection of the agents is at the treating physician's discretion. Patients with HER 2 positive disease should complete a total of one year of trastuzumab therapy (over the neoadjuvant and adjuvant period). Chemotherapy, biologic therapy or vaccine therapy in the adjuvant setting is not allowed. Patients who wish to receive any of these therapies after surgery must go off study at the time of their initiation. Ancillary Therapy: Patients should receive full supportive care, including transfusions of blood and blood products, erythropoetin (unless otherwise specified in the protocol), antibiotics, antiemetics, etc. when appropriate. Patients are followed up for 5 years after completion of radiation therapy.

    TRIAL NUMBER: A011401

    Title: A011401: Study Title for Study Participants: Breast Cancer WEight Loss Study (BWEL Study) Official Study Title for Internet Search on http://www.ClinicalTrials.gov: Randomized Phase III Trial Evaluating the Role of Weight Loss in Adjuvant Treatment of Overweight and Obese Women with Early Breast Cancer

    Purpose: This study is being done to see if losing weight may help prevent breast cancer from coming back (recurring). Previous studies have found that women who are overweight or obese when their breast cancer is found (diagnosed) have a greater risk of their breast cancer recurring, as compared to women who were thinner when their cancer was diagnosed. At this time we do not know whether or not losing weight will reduce the risk of breast cancer returning. This study seeks to determine whether or not the higher risk for breast cancer recurrence in women who are overweight or obese when they are diagnosed with breast cancer could be reduced or eliminated if weight is lost. It is important to note that we do not know how much weight would need to be lost to lower the risk of breast cancer recurrence, or whether this strategy would work for all women. This study will help to show us whether weight loss programs should be a part of breast cancer treatment.

    TRIAL NUMBER: A221505

    Title: PHASE III RANDOMIZED TRIAL OF HYPOFRACTIONATED POST MASTECTOMY RADIATION WITH BREAST RECONSTRUCTION

    Purpose: 2.1 Primary Objective To evaluate whether the reconstruction complication rate at 24 months post radiation is non-inferior with hypofractionation. Complications will include those listed in Section 10.1. 2.2 Secondary Objectives 2.2.1 To evaluate the incidence of acute and late radiation complications based on CTCAE 4.0 toxicity. 2.2.2 To evaluate the local and local regional recurrence rate. 2.2.3 To compare reconstruction complication rates based on reconstruction method (autologous +/- implant vs implant only) and timing of reconstruction received (immediate vs. intent for delayed).

    TRIAL NUMBER: EA1131

    Title: A Randomized Phase III Post-Operative Trial of Platinum Based Chemotherapy Vs. Observation in Patients with Residual Triple-Negative Basal-Like Breast Cancer following Neoadjuvant Chemotherapy

    Purpose: The purpose of this study is to compare the IDFS in TNBC patients with residual basal-like disease after neoadjuvant chemotherapy who are randomized to post-preoperative platinum based chemotherapy with those who are randomized to observation. At present, upon completion of neoadjuvant therapy, the standard of care for patients with TNBC (who have no clinical evidence of metastatic disease after surgical excision of the cancer regardless of burden of residual disease) is observation, since there is no additional therapies available with proven impact. This study could provide a possible alternative treatment, which makes it appropriate for the population.

    TRIAL NUMBER: NRG-BR003

    Title: A Randomized Phase III Trial of Adjuvant Therapy Comparing Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel With or Without Carboplatin for Node-Positive or High-Risk Node-Negative Triple-Negative Invasive Breast Cancer

    Purpose: This randomized phase III trial studies how well doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel with or without carboplatin work in treating patients with triple-negative breast cancer. Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether doxorubicin hydrochloride and cyclophosphamide is more effective when followed by paclitaxel alone or paclitaxel and carboplatin in treating triple-negative breast cancer.

    TRIAL NUMBER: NSABP B-51

    Title: A Randomized Phase III Clinical Trial Evaluating Post-Mastectomy Chestwall and Regional Nodal XRT and Post-Lumpectomy Regional Nodal XRT in Patients With Positive Axillary Nodes Before Neoadjuvant Chemotherapy Who Convert to Pathologically Negative Axillary Nodes After Neoadjuvant Chemotherapy

    Purpose: This randomized phase III trial studies standard or comprehensive radiation therapy in treating patients with early-stage breast cancer who have undergone surgery. Radiation therapy uses high-energy x rays to kill tumor cells. It is not yet known whether comprehensive radiation therapy is more effective than standard radiation therapy in treating patients with breast cancer

    TRIAL NUMBER: S1501

    Title: PROSPECTIVE EVALUATION OF CARVEDILOL IN PREVENTION OF CARDIAC TOXICITY IN PATIENTS WITH METASTATIC HER-2+ BREAST CANCER, PHASE III

    Purpose: Primary Objective To assess whether prophylactic beta blocker therapy with carvedilol compared with no intervention reduces the risk of subsequent cardiac dysfunction in patients with metastatic breast cancer receiving trastuzumab?based HER-2 targeted therapy. Secondary Objectives a. To assess whether prophylactic beta blocker therapy with carvedilol compared with no intervention reduces the risk of predefined subsequent cardiac events in patients with metastatic breast cancer receiving trastuzumab?based HER-2 targeted therapy. b. To evaluate if prophylactic carvedilol compared with no intervention results in a longer time to first interruption of trastuzumab?based HER-2 targeted therapy due to either cardiac dysfunction or events. c. To assess whether prophylactic beta blocker therapy with carvedilol compared with no intervention reduces the risk of subsequent cardiac dysfunction OR events in this population. d. To establish and prospectively collect a predefined panel of baseline core cardiovascular measures and develop a predictive model of cardiac dysfunction (see Section 11.2). e. To evaluate the rate of cardiac dysfunction in an observational arm consisting of individuals otherwise eligible for the study except for use of beta blockers, angiotensin receptor blocker (ARB), or angiotensin converting enzyme (ACE) inhibitors for other medical reasons.

    TRIAL NUMBER: WF 97116

    Title: Phase 3 Randomized Placebo Controlled Clinical Trial of Donepezil - WF 97116

    Purpose: This study is to compare the safety and effects of donepezil (Aricept) or if it decreases memory loss after receiving chemotherapy for breast cancer.

    TRIAL NUMBER: ALTE11C2

    Title: HEALTH EFFECTS AFTER ANTHRACYCLINE AND RADIATION THERAPY (HEART): DEXRAZOXANE AND PREVENTION OF ANTHRACYCLINE-RELATED CARDIOMYOPATHY

    Purpose: Given the critical role anthracyclines have in many effective cancer treatments and the risk for subsequent cardiotoxicity associated with this class of agents, development of an effective cardioprotective strategy is of great importance. Although adult studies have shown that dexrazoxane (DRZ) is effective in minimizing cardiomyopathy/heart failure (CHF) after anthracycline therapy, short and long-term data in children are much more limited. Furthermore, concerns regarding DRZ's interaction with cancer therapies and possible association with an increased risk of second cancers have limited its use among children despite possible protection against premature CHF. To address these gaps in knowledge, using a cross-sectional study design, we propose to ascertain echocardiographic and serum biomarkers of cardiac injury in a cohort of long-term pediatric T-cell leukemia and Hodgkin lymphoma survivors enrolled on 3 front-line Children's Oncology Group (COG) clinical trials (POG 9404, 9425, 9426) between 1996-2001 that featured upfront DRZ randomization and a range of anthracycline exposures commonly used in contemporary therapy (100-360 mg/m2 doxorubicin). Our primary aim will be to determine whether patients randomized to the experimental DRZ arms have decreased markers of myocardial injury compared with patients treated without DRZ. Specifically, this will include a one-time measurement of an echocardiographic index of pathologic left ventricular (LV) remodeling (wall thickness-dimension ratio), complemented by serum biomarkers and a physical examination for signs and symptoms of CHF. We will also evaluate whether DRZ's cardioprotective effect is modified by anthracycline dose, chest radiation, and selected demographic factors (age at cancer diagnosis, current age, sex). In secondary analysis, we will also update the overall- and event-free survival rates between patients on the DRZ and non-DRZ arms. Finally, we will determine whether projected quality-adjusted life years differed by randomization status, accounting for premature cardiac disease, primary disease relapse, and second cancers.

    TRIAL NUMBER: DCP-001

    Title: DCP-001, Use of a Clinical Trial Screening Tool to Address Cancer Health Disparities in the NCI Community Oncology Research Program (NCORP)

    Purpose: The protocol is not a scientific study; rather, a method to implement the screening tool and allow the collection and analyses of expanded data with informed consent. Investigators also enroll patients into NCI-treatment trials. The tool, based on a screening log successfully used within the NCI Community Cancer Centers Program (NCCCP), has been streamlined and integrated into the sites’ workflow by using OPEN. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. Also missing from the existing data is the context of care, within the communities themselves where most cancer and at risk of cancer patients receive care which is the focus of NCORP. The profile of patients accrued to NCI-sponsored clinical trials lacks both racial/ethnic and socioeconomic diversity. Accrued patients tend to be insured, highly educated and of higher socioeconomic means. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. NCORP's clinical trials portfolio includes cancer control, prevention, screening, symptom science, and cancer care delivery research.

    TRIAL NUMBER: WF-10217

    Title: Work Ability in Young Adult Survivors (WAYS)

    Purpose: Brief Summary: To document levels of labor force participation, occupation, educational attainment, and financial toxicity following cancer treatment in YA cancer survivors aged 25-34 years.
    Detailed Description: This observational, cross-sectional study will recruit 200 YA survivors through the Wake Forest National Cancer Institute Community Oncology Research Program (NCORP) Research Base (WF NCORP RB). Data will be collected using a web-based interface and will capture physical, psychosocial and cognitive late effects; work ability; work-related outcomes, including labor force participation, occupation, work place characteristics, and educational attainment; survivor characteristics; and cancer diagnosis/treatment information (from clinical records). We will evaluate the relationships among these measures using the theoretical framework to guide statistical analysis.

    TRIAL NUMBER: A021502

    Title: Randomized Trial of Standard Chemotherapy Alone or Combined With Atezolizumab as Adjuvant Therapy for Patients With Stage III Colon Cancer and Deficient DNA Mismatch Repair

    Purpose: This randomized phase III trial studies combination chemotherapy and atezolizumab to see how well it works compared with combination chemotherapy alone in treating patients with stage III colon cancer and deficient deoxyribonucleic acid (DNA) mismatch repair. Drugs used in combination chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as atezolizumab, may interfere with the ability of tumor cells to grow and spread. Giving combination chemotherapy with atezolizumab may work better than combination chemotherapy alone in treating patients with colon cancer.

    TRIAL NUMBER: EA2174

    Title: A PHASE II/III STUDY OF PERI-OPERATIVE NIVOLUMAB AND IPILIMUMAB IN PATIENTS WITH LOCOREGIONAL ESOPHAGEAL AND GASTROESOPHAGEAL JUNCTION ADENOCARCINOMA

    Purpose: Primary Outcome Measures : Pathologic complete response (Step I) [ Time Frame: Up to 5 weeks ] The study with compare the pathologic complete response of Arm A and Arm B using a one-sided 0.10 level chi-squared test for proportions.
    Disease-free survival (DFS) (Step 2) [ Time Frame: From the adjuvant treatment randomization assessed for up to 7 years ] DFS measured from the adjuvant treatment randomization will be the endpoint of the adjuvant portion of the study and to achieve the desired power it is expected that patients will be followed for an additional year post completion of accrual to the adjuvant portion. The DFS comparison will be between patients randomized to Arm C (nivolumab) versus Arm D (nivolumab plus ipilimumab) using a one-sided 0.10 level stratified log rank test.

    Secondary Outcome Measures : Incidence of adverse events [ Time Frame: Up to 7 years ] Graded according to Common Terminology Criteria for Adverse Events version 5.0. Toxicity will be evaluated among all treated patients regardless of eligibility and interim analyses of toxicity are performed twice yearly. The study will have sufficient precision to provide 95% confidence intervals on toxicity
    Overall survival [ Time Frame: From the time of first randomization up to 7 years ] Analyses will be descriptive in nature and will not follow any formal interim monitoring.
    DFS [ Time Frame: From the time of first randomization up to 7 years ] The DFS comparison will be between patients randomized to Arm C (nivolumab) versus Arm D (nivolumab plus ipilimumab) using a one-sided 0.10 level stratified log rank test.

    Other Outcome Measures: Percent change in mean volumetric apparent diffusion coefficient (ADC) [ Time Frame: Baseline to mid-treatment ] The study will assess the area under the receiver operating characteristic curve of the changes of apparent diffusion coefficient (ADC) value.

    TRIAL NUMBER: S1815

    Title: A PHASE III RANDOMIZED TRIAL OF GEMCITABINE, CISPLATIN, AND NAB-PACLITAXEL VERSUS GEMCITABINE AND CISPLATIN IN NEWLY DIAGNOSED, ADVANCED BILIARY TRACT CANCERS

    Purpose: Primary Outcome Measures : Overall survival (OS) [ Time Frame: Up to 3 years ] OS will be determined using the log-rank test with stratification by disease site (gallbladder adenocarcinoma versus [vs.] intrahepatic cholangiocarcinoma vs. extrahepatic cholangiocarcinoma), disease stage (locally advanced vs. metastatic), and Zubrod performance status (0 vs. 1). Distributions of overall survival by treatment arm will be estimated using the method of Kaplan-Meier.

    Secondary Outcome Measures : Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: Up to 3 years ] Rates of serious toxicities will be compared between arms.
    Progression-free survival (PFS) [ Time Frame: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years ] Distributions of PFS will be described using cumulative incidence estimates with differences in these estimates between treatment arms assessed by a stratified Cox regression model.
    Overall response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria [ Time Frame: Up to 3 years ] ORR is defined as confirmed and unconfirmed; complete response + partial response + stable disease. The chi-square test will be used to compare ORR, disease control rate (DCR), and rates of toxicity events across arms. ORR will be assessed in the subset of patients with measurable disease.
    Disease control rate as measured by RECIST 1.1 criteria [ Time Frame: Up to 3 years ] The chi-square test will be used to compare ORR, DCR, and rates of toxicity events across arms. Disease control includes confirmed and unconfirmed complete response, confirmed and unconfirmed partial response, and stable disease. In patients with non-measurable disease, disease control will be defined as those who are alive without disease progression.
    Changes in carbohydrate antigen 19-9 (CA 19-9) levels [ Time Frame: Baseline up to course 3 ] Correlations between changes in CA19-9 levels from baseline to post-treatment and ORR will be estimated via logistic regression models, both within each treatment arm and in the overall cohort. Analyses will explore the prognostic and predictive values of CA19-9 for disease response.

    TRIAL NUMBER: NRG-GY006

    Title: A Randomized Phase II Trial of Radiation Therapy and Cisplatin Alone or in Combination with Intravenous Triapine in Women with Newly Diagnosed Bulky Stage IB2, Stage II, IIIB, or IVA Cancer of the Uterine Cervix or Stage II-IVA Vaginal Cancer

    Purpose: This randomized phase II trial studies radiation therapy and cisplatin with triapine to see how well they work compared to the standard radiation therapy and cisplatin alone in treating patients with newly diagnosed stage IB2, II, or IIIB-IVA cervical cancer or stage II-IVA vaginal cancer. Radiation therapy uses high energy protons to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether radiation therapy and cisplatin are more effective with triapine in treating cervical or vaginal cancer.

    TRIAL NUMBER: EA2142

    Title: Randomized Phase II Study of Cisplatin and Etoposide Versus Temozolomide and Capecitabine in Patients With Advanced G3 Non-small Cell Gastroenteropancreatic Neuroendocrine Carcinomas

    Purpose: This randomized phase II trial studies how well temozolomide and capecitabine work compared to standard treatment with cisplatin and etoposide in treating patients with neuroendocrine carcinoma of the gastrointestinal tract or pancreas that has spread to other parts of the body (metastatic) or cannot be removed by surgery. Drugs used in chemotherapy, such as temozolomide, capecitabine, cisplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Certain types of neuroendocrine carcinomas may respond better to treatments other than the current standard treatment of cisplatin and etoposide. It is not yet known whether temozolomide and capecitabine may work better than cisplatin and etoposide in treating patients with this type of neuroendocrine carcinoma, called non-small cell neuroendocrine carcinoma.

    TRIAL NUMBER: A041701

    Title: A Randomized Phase II/III Study of Conventional Chemotherapy +/- Uproleselan (GMI-1271) in Older Adults With Acute Myeloid Leukemia Receiving Intensive Induction Chemotherapy

    Purpose: This phase II/III trial studies how well daunorubicin and cytarabine with or without uproleselan works in treating older adult patients with acute myeloid leukemia receiving intensive induction chemotherapy. Drugs used in chemotherapy, such as daunorubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Uproleselan may prevent cancer from returning or getting worse. Giving daunorubicin and cytarabine with uproleselan may work better in treating patients with acute myeloid leukemia compared to daunorubicin and cytarabine alone.

    TRIAL NUMBER: APEC14B1

    Title: Project: Every Child for Younger Patients With Cancer

    Purpose: This research trial studies the Project: Every Child for younger patients with cancer. Gathering health information over time from younger patients with cancer may help doctors find better methods of treatment and on-going care.

    TRIAL NUMBER: ARST1431

    Title: COG ARST1431, A Randomized Phase 3 Study of Vincristine, Dactinomycin, Cyclophosphamide (VAC) Alternating with Vincristine and Irinotecan (VI) Versus VAC/VI Plus Temsirolimus (TORI, Torisel, NSC# 683864, IND# 122782) in Patients with Intermediate Risk (IR) Rhabdomyosarcoma (RMS)

    Purpose: ARST1431, states that Unfortunately about 25% of patients with intermediate-risk (IR) embryonal rhabdomyosarcoma (ERMS) and 50% of those with IR alveolar rhabdomyosarcoma (ARMS) will experience disease recurrence with a resulting long-term event-free survival (EFS) of 65%. The mTOR pathway is important in RMS biology, and temsirolimus (TORI), an mTOR inhibitor, has demonstrated clinical activity in patients with relapsed RMS. In an attempt to improve long-term survival for patients with IR RMS, ARST1431 will compare the EFS of patients with newly diagnosed IR RMS randomly assigned to standard vincristine, dactinomycin, and cyclophosphamide (VAC) alternating with vincristine and irinotecan (VI) versus VAC/VI plus TORI. Radiotherapy will start at Week 13 of therapy for all patients. Correlative biology studies will be performed including a determination of the FOXO1 gene fusion status in the tumor and impact on patient outcome. Children’s Hospital/LSUHSC-NO sees several diagnosed patients with Intermediate Risk (IR) Rhabdomyosarcoma (RMS), We estimate seeing up to 5-10 patients per year.

    TRIAL NUMBER: AALL1331

    Title: Risk-Stratified Randomized Phase III Testing of Blinatumomab (IND #117467, NSC #765986) in First Relapse of Childhood B-Lymphoblastic Leukemia (B-ALL): A Groupwide Phase III Study

    Purpose: PRIMARY OBJECTIVES:
    I. To compare disease free survival (DFS) of high-risk (HR) and intermediate-risk (IR) relapse B-cell acute lymphoblastic leukemia (B-ALL) patients who are randomized following induction block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR randomization).
    II. To compare the DFS of low risk (LR) relapse B-ALL patients who are randomized following block 2 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR randomization).
    SECONDARY OBJECTIVES:
    I. To compare overall survival (OS) of HR and IR relapse B-ALL patients who are randomized following induction block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR randomization).
    II. To compare OS of LR relapse B-ALL patients who are randomized following block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR randomization).
    TERTIARY OBJECTIVES:
    I. To compare the rates of minimal residual disease (MRD) >= 0.01% at the end of block 2 and block 3 for HR and IR relapse B-ALL patients in HR/IR randomization.
    II. To estimate, for treatment failure (TF) patients not previously receiving blinatumomab, the hematologic complete remission rate (CR), rate of MRD < 0.01%, and proportion able to proceed to hematopoietic stem cell transplant (HSCT) in CR after treatment with blinatumomab.
    III. To assess the feasibility and safety of rapid taper of immune suppression for the subset of HSCT patients with MRD >= 0.01% pre- and/or post-HSCT with no acute graft versus host disease (aGVHD).
    OUTLINE:
    All patients receive Block 1 over 4 weeks.
    BLOCK 1: Patients receive dexamethasone orally (PO) twice daily (BID) or intravenously (IV) on days 1-5 and 15-19; vincristine sulfate IV over 1 minute on days 1, 8, 15, and 22; pegaspargase IV over 1-2 hours on days 3 and 17; and mitoxantrone hydrochloride IV over 15-30 minutes on days 1-2. Patients with central nervous system (CNS) 1 or CNS2 also receive methotrexate intrathecally (IT) on days 1 and 8. Patients with CNS3 or isolated CNS relapse also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 1, 8, 15, and 22. High risk and intermediate risk patients are then assigned to randomization R1. Low risk patients are assigned to randomization R2.
    RANDOMIZATION R1 (HR and IR patients): Patients are randomized to 1 of 2 treatment arms.
    ARM A: Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, and then undergo allogeneic HSCT.
    ARM B: Patients receive Blinatumomab Block 1 over 5 weeks, Blinatumomab Block 2 over 5 weeks, and then undergo allogeneic HSCT.
    RANDOMIZATION R2 (LR patients): Patients are then randomized to 1 of 2 treatment arms.
    ARM C: Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, Continuation 1 over 8 weeks, Continuation 2 over 8 weeks, and then Maintenance.
    ARM D: Patients receive Block 2 over 4 weeks, Blinatumomab Block 2 over 5 weeks, Continuation 1 over 8 weeks, Blinatumomab Block 3 over 5 weeks, Continuation 2 over 8 weeks, Blinatumomab Block 3 over 5 weeks, and then Maintenance.
    BLOCK 2: Patients receive dexamethasone PO BID or IV on days 1-5; vincristine sulfate IV over 1 minute on day 1; methotrexate IV over 36 hours on day 8; leucovorin calcium IV or PO on days 9-10; pegaspargase IV over 1-2 hours on day 9; cyclophosphamide IV over 15-30 minutes on days 15-19; and etoposide IV over 1-2 hours on days 15-19. Patients with CNS1 or CNS2 also receive methotrexate IT on day 8. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 8 and 22.
    BLOCK 3: Patients receive dexamethasone PO BID or IV on days 1-5; vincristine sulfate IV over 1 minute on day 1; cytarabine IV over 3 hours every 12 hours on days 1, 2, 8, and 9; asparaginase intramuscularly (IM) on days 2, 4, 9, 11, and 23; methotrexate IT on day 1 and IV over 36 hours on day 22; leucovorin calcium PO or IV on days 23-24. Patients with CNS1 or CNS2 also receive methotrexate IT on day 22. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 1 and 22.
    BLINATUMOMAB BLOCK 1: Patients blinatumomab IV continuously on days 1-28 and dexamethasone PO or IV on day 1. Patients with CNS1 or CNS2 also receive methotrexate IT on days 15 and 29. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 15 and 29.
    BLINATUMOMAB BLOCK 2: Patients blinatumomab IV continuously on days 1-28 and dexamethasone PO or IV on day 1. Patients with CNS1 or CNS2 also receive methotrexate IT on days 8 and 29. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 8 and 29.
    BLINATUMOMAB BLOCK 3: Patients blinatumomab IV continuously on days 1-28 and dexamethasone PO or IV on day 1.
    CONTINUATION 1 & 2: Patients receive dexamethasone PO BID or IV on days 1-5; vincristine sulfate IV over 1 minute on day 1; mercaptopurine tablet PO on days 1-42; methotrexate PO on days 8, 15, 29, and 36; leucovorin calcium PO or IV on days 23-24; cyclophosphamide IV over 15-30 minutes on days 42 and 49; etoposide IV over 1-2 hours on days 42 and 49; thioguanine PO once daily on days 42-48; and cytarabine IV or subcutaneously (SC) on days 43-46 and 50-53. Patients with CNS1 or CNS2 also receive methotrexate IT on days 1 and 43. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 1 and 43; methotrexate PO every 6 hours on day 22; and methotrexate IV over 36 hours on day 22.
    MAINTENANCE: Patients receive dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61; vincristine sulfate IV over 1 minute on days 1, 29, and 57; mercaptopurine tablet PO on days 1-84; and methotrexate PO on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Patients with CNS1 or CNS2 also receive methotrexate IT on day 1. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 1. Courses repeat every 12 weeks for up to 2 years since the beginning of treatment in the absence of disease progression or unacceptable toxicity.
    After completion of study treatment, patients are followed up annually for 10 years.

    TRIAL NUMBER: A031704

    Title: PD-Inhibitor (Nivolumab) and Ipilimumab Followed by Nivolumab Vs. VEGF TKI Cabozantinib with Nivolumab: A Phase III Trial in Metastatic Untreated REnal Cell CancEr [PDIGREE]

    Purpose: This phase III trial studies how well nivolumab and ipilimumab, followed by nivolumab versus cabozantinib and nivolumab, work in treating patients with renal cell cancer that is untreated and has spread to other parts of the body. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cabozantinib, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known how well cabozantinib and nivolumab work in treating patients with untreated renal cell cancer that has spread to other parts of the body.

    TRIAL NUMBER: AREN03B2

    Title: RENAL TUMORS CLASSIFICATION, BIOLOGY, AND BANKING STUDY

    Purpose: PRIMARY OBJECTIVES:
    I. Classify patients with renal tumors by histological categorization, surgico- pathological stage, presence of metastases, age at diagnosis, tumor weight, and loss of heterozygosity for chromosomes 1p and 16q, to define eligibility for a series of therapeutic studies.
    II. Maintain a biological samples bank to make specimens available to scientists to evaluate additional potential biological prognostic variables and for the conduct of other research by scientists.
    SECONDARY OBJECTIVES:
    I. Monitor outcome for those patients who are not eligible for a subsequent therapeutic study.
    II. Describe whether the pulmonary tumor burden correlates with outcome in patients with stage IV disease.
    III. Describe the sensitivity and specificity of abdominal computed tomography (CT) scan by comparing it with surgical and pathologic findings for identification of local tumor spread beyond the renal capsule to adjacent muscle and organs, lymph node involvement at the renal hilum and in the retroperitoneum, preoperative tumor rupture, and metastases to the liver.
    IV. Compare the sensitivity and specificity of pre-operative abdominal CT scan and MRI for the identification and differentiation of nephrogenic rests and Wilms' tumor in children with multiple renal lesions.
    V. Correlate the method of conception (natural vs assisted reproductive technology) with the development of Wilms' tumor.
    OUTLINE: This is a multicenter study.
    Tumor tissue, blood, and urine samples are collected for research studies, including immunohistochemistry. CT scans and magnetic resonance imaging (MRIs) are also performed. Loss of heterozygosity analyses (chromosome 1p and 16q) are performed by extraction of DNA. DNA polymorphisms are assayed by polymerase chain reaction using standard methodology. Leftover specimens are archived for future studies.
    Patients are followed periodically for 5 years.

    TRIAL NUMBER: A041501

    Title: A PHASE III TRIAL TO EVALUATE THE EFFICACY OF THE ADDITION OF INOTUZUMAB OZOGAMICIN (A CONJUGATED ANTI-CD22 MONOCLONAL ANTIBODY) TO FRONTLINE THERAPY IN YOUNG ADULTS (AGES 18-39 YEARS) WITH NEWLY DIAGNOSED PRECURSOR B-CELL ALL

    Purpose: Primary Outcome Measures : EFS [ Time Frame: Time from induction response to the time of progressive-disease, secondary malignancy, or death, assessed up to 3 years ] Will be compared using log-rank tests. EFS curves will be constructed using the Kaplan-Meier product limit method, and additional analyses will be done using the Cox proportional hazards model. The corresponding hazard ratio, 2- and 3-year EFS estimates will be assessed, and EFS medians along with their 95% confidence intervals for the two treatment arms.

    Secondary Outcome Measures : DFS [ Time Frame: Time from achievement of CR to the time of relapse and/or death, assessed up to 10 years ] OS [ Time Frame: Time from randomization to the time of death due to any cause, assessed up to 10 years ] Will be evaluated using Kaplan-Meier as well as Cox regression models.
    Proportion of patients who achieve CR or any response to induction therapy [ Time Frame: Up to 10 years ] Will be summarized as the proportion of patients who achieve any type of response to induction therapy divided by the number of all evaluable patients registered to this trial and who received at least one dose of induction therapy. Corresponding 95% binomial confidence intervals will also be calculated.
    Overall induction response rates [ Time Frame: Up to 10 years ] Will be summarized as the proportion of patients who achieve any type of response to induction therapy divided by the number of all evaluable patients registered to this trial and who received at least one dose of induction therapy. Corresponding 95% binomial confidence intervals will also be calculated.
    Incidence of adverse events as assessed by Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 10 years ] The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. In addition, all adverse event data that is graded as 3, 4, or 5 will be reviewed and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The incidence of severe (grade 3+) adverse events or toxicities will be described for each treatment arm, but will also be compared between the arms. Fisher's exact tests will be used to quantitatively compare the incidence of severe as well as specific toxicities of interest between the treatment arms and we will graphically assess differences in maximum grades observed for toxicities between the arms. Tolerability of the treatment arms will be assessed through assessing the number of patients who required dose modifications and/or dose delays.
    Proportion of patients who go off treatment due to adverse reactions [ Time Frame: Up to 10 years ] Will be assessed within each of the treatment arms and differences explores in these measures between the arms.
    Proportion of patients who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial [ Time Frame: Up to 10 years ] Will be assessed within each of the treatment arms and differences explores in these measures between the arms.

    TRIAL NUMBER: AALL15P1

    Title: A GROUPWIDE PILOT STUDY TO TEST THE TOLERABILITY AND BIOLOGIC ACTIVITY OF THE ADDITION OF AZACITIDINE TO CHEMOTHERAPY IN INFANTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) AND KMT2A (MLL) GENE REARRANGEMENT

    Purpose: Primary Outcome Measures: Incidence of adverse events of azacitidine and combination chemotherapy, graded according to Common Terminology Criteria for Adverse Events 4.0 [ Time Frame: From the first course of azacitidine administration up to fourth course of azacitidine administration ]
    Secondary Outcome Measures: Biologic activity, defined as global DNA methylation change in PBMCs [ Time Frame: Prior to first course of azacitidine up to day 5 of second course of azacitidine ] Will calculate the mean long interspersed nucleotide element-1 (LINE-1) methylation for all patients before and after azacitidine and perform paired t-test analysis to determine if there is significant demethylation in the study population for the tested dose level.

    Other Outcome Measures: EFS [ Time Frame: From time of enrollment up to 5 years ] Descriptive analysis will be conducted to correlate MRD with the EFS for the KMT2A-R patients. PD data for asparaginase activity following pegaspargase administration in infants will be collected and correlated with EFS for the KMT2A-R patients. Standard errors and confidence intervals for EFS will be calculated using Peto's method.
    Expansion of infant T lymphocytes by stimulation with artificial antigen presenting cells [ Time Frame: Up to the end of consolidation therapy, assessed up to 5 years ] Minimal residual disease [ Time Frame: Up to 5 years ] Descriptive analysis will be conducted to correlate MRD with the EFS for the KMT2A-R patients.
    PD data for asparaginase activity following pegaspargase administration [ Time Frame: From 7 days following pegaspargase administration during induction therapy up to 7 days following pegaspargase administration during delayed intensification part 2 ] Will be collected and correlated with EFS for the KMT2A-R patients
    PK parameters of azacitidine [ Time Frame: Pre-dose on days 3 and 4, at 5 and 30 minutes, and 1, 4, and 6 hours post-dose of azacitidine block I ]

    TRIAL NUMBER: AAML1531

    Title: RISK-STRATIFIED THERAPY FOR ACUTE MYELOID LEUKEMIA IN DOWN SYNDROME

    Purpose: PRIMARY OBJECTIVES:
    I. To determine the 2-year event-free-survival (EFS) for children with standard risk Down syndrome (DS) acute myeloid leukemia (AML) (minimal residual disease [MRD]-negative after one cycle of induction therapy) after elimination of high dose (HD) Ara-C (cytarabine) from the treatment regimen.
    II. To determine the 2-year EFS for children with high risk DS AML (MRD-positive after one cycle of induction therapy) after intensification of treatment equivalent to that used for high risk AML in children without DS.
    EXPLORATORY OBJECTIVES:
    I. To determine the extent to which elimination of HD Ara-C from the treatment of standard risk DS AML decreases adverse events and resource utilization.
    II. To determine if elimination of HD Ara-C from treatment of standard risk DS AML results in a significant decrease in the number of days per patient spent on protocol therapy compared to predecessor study AAML0431.
    III. To determine if elimination of HD Ara-C from treatment of standard risk DS AML results in a significant decrease in the average number of days of hospitalization per patient compared to predecessor studies AAML0431 and A2971.
    IV. To determine if elimination of HD Ara-C from treatment of standard risk DS AML results in a significant decrease in the number (per patient) and rate (per duration of treatment) of sterile site infections compared to the predecessor study AAML0431.
    V. To determine if elimination of HD Ara-C from treatment of standard risk DS AML results in a significant decrease of resource utilization by AML treatment compared to the predecessor study AAML0431.
    VI. To compare the feasibility and analytical characteristics of flow cytometry, polymerase chain reaction (PCR) and targeted error-corrected sequencing of GATA binding protein 1 (globin transcription factor 1) (GATA1) mutations as methods to detect MRD in DS AML.
    VII. To establish a DS AML cell bank of viably frozen bone marrow samples collected at the end of induction and corresponding non-tumor deoxyribonucleic acid (DNA) samples collected at end of Induction 1.
    OUTLINE:
    INDUCTION I: Patients receive cytarabine intrathecally (IT) on day 1 and intravenously (IV) continuously over 96 hours, daunorubicin hydrochloride IV over 1-15 minutes, and thioguanine orally (PO) twice daily (BID) on days 1-4. Induction I continues for a minimum of 28 days.
    Patients are assigned to 1 of 2 treatment arms based on their MRD status after completion of Induction I.
    ARM A (STANDARD RISK):
    INDUCTION II: Patients receive cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV over 1-15 minutes, and thioguanine PO BID on days 1-4. Induction II continues for a minimum of 28 days.
    INDUCTION III: Patients receive cytarabine, daunorubicin hydrochloride, and thioguanine as in Induction II. Induction III continues for a minimum of 28 days.
    INTENSIFICATION I: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 60-120 minutes on days 1-3. Intensification I continues for a minimum of 28 days.
    INTENSIFICATION II: Patients receive cytarabine and etoposide as in Intensification I. Intensification II continues for a minimum of 28 days.
    ARM B (HIGH RISK):
    INDUCTION II: Patients receive high dose cytarabine IV over 1-3 hours BID on days 1-4 and mitoxantrone hydrochloride IV over 15-30 minutes on days 3-6. Induction II continues for a minimum of 28 days.
    INTENSIFICATION I: Patients receive high dose cytarabine IV over 1-3 hours BID and etoposide IV over 60-120 minutes on days 1-5. Intensification I continues for a minimum of 28 days.
    INTENSIFICATION II: Patients receive high dose cytarabine IV over 3 hours BID on days 1, 2, 8, and 9. Patients also receive asparaginase or asparaginase Erwinia chrysanthemi (E. carotovora) intramuscularly (IM) or IV over 30 minutes on days 2 and 9. Intensification II continues for a minimum of 28 days.
    After completion of study treatment, patients are followed up at 1 month, monthly for 12 months, every 3 months for 12 months, every 6 months for 3 years, annually for 5 years, and then at relapse.

    TRIAL NUMBER: ACCL16N1CD

    Title: Documentation and Delivery of Guideline-Consistent Treatment in Adolescent and Young Adult (AYA) Acute Lymphoblastic Leukemia (ALL)

    Purpose: This research trial studies cancer care delivery in adolescent and young adult patients with acute lymphoblastic leukemia. Surveying institutions, evaluating delivery of care at the patient level and seeking input from healthcare providers may help doctors increase rates of adherence to National Comprehensive Cancer Network (NCCN) treatment guidelines. It may also improve care for adolescent and young adult patients with acute lymphoblastic leukemia.
    PRIMARY OBJECTIVES:
    I. To evaluate the proportion of adolescent and young adult (AYA) acute lymphoblastic leukemia (ALL) patients with a documented treatment plan consistent with NCCN guidelines for AYAs with ALL.
    II. To evaluate the proportion of AYA ALL patients whose delivered treatment during induction and post-induction therapy (PIT) is consistent with NCCN guidelines for AYAs with ALL.
    III. To determine the impact of treating physician specialty and facility type on likelihood of AYA ALL patients having a documented treatment plan concordant with NCCN guidelines when stratified by age group (15-17year[y], 18-21y, and 22-39y).
    IV. To determine the impact of treating physician specialty and facility type on the likelihood of AYA ALL patients receiving induction and post-induction therapy (PIT) concordant with NCCN guidelines when stratified by age group (15-17y, 18-21y, and 22-39y).
    V. To identify for AYAs with ALL, targetable structure- and process-level barriers and facilitators which will increase the proportion of patients having a documented treatment plan and receiving treatment according to NCCN guidelines.
    SECONDARY OBJECTIVES:
    I. To explore potential correlations with clinical and social demographic variables to the presence of a documented treatment plan and delivered treatment consistent with NCCN guidelines in AYAs with ALL.
    OUTLINE:
    CHART REVIEW: Patient medical record data is abstracted and treatment plans are reviewed for consistency to NCCN guidelines. For each patient, induction and post-induction care is recorded as either concordant with NCCN guidelines or non-concordant with NCCN guidelines.
    SITE QUESTIONNAIRE: Participating sites complete a questionnaire which is designed to capture facility-oriented data.
    FOCUS GROUPS: Healthcare providers participate in focus groups over 1-2 hours to discuss facilitators and barriers to AYA ALL guideline concordance. Participants provide responses via electronic handheld technology in order to maintain anonymity followed by discussion of the ideas for clarification.

    TRIAL NUMBER: ALTE1631

    Title: A RANDOMIZED WEB-BASED PHYSICAL ACTIVITY INTERVENTION AMONG CHILDREN AND ADOLESCENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

    Purpose:

    Primary Outcome Measures :
    1. Physiologic cost index (PCI) [ Time Frame: Up to 24 weeks (end of intervention) ]
      Differences in PCI will be compared between groups at the end of the intervention. Intent to treat analysis of variance (either transforming the data or employing a non-parametric equivalent if the data are not normally distributed) controlling for the stratification factors (sex, age, and treatment related risk group) will be used for comparison. General linear mixed models will be utilized to evaluate the effects of group assignment on changes in PCI over time to account for repeated measures on individual children, and for potential random effects such as original treating institution.


    Secondary Outcome Measures :
    1. Change in markers of cardiometabolic health [ Time Frame: Baseline up to 48 weeks post intervention ]
      Markers of Cardiometabolic health include blood pressure, body mass index, waist to height ration, fasting insulin, glucose, and lipid levels. Differences in these markers between randomized groups and the effects of group assignment on changes over time will be evaluated.

    2. Change in inflammation [ Time Frame: Baseline up to 48 weeks post intervention ]
      Markers of an Inflammatory state include High sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor alpha. Differences in these markers between groups and the effects of group assignment on changes over time will be evaluated.

    3. Change in quality of life assessed using Pediatric Quality of Life (PedsQL) 4.0 Generic Core Scale [ Time Frame: Baseline up to 48 weeks post intervention ]
      The 23-item PedsQL Generic Core Scales were designed to measure the core dimensions of health as delineated by the World Health Organization, as well as role (school) functioning. Scores range from 0-100, higher is better.. There are four scales (Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning).. Emotional, Social and School Functioning can be combined to create a psychosocial summary (summed and divided by total number of items). Differences between groups and the effects of group assignment on changes over time will be evaluated.

    4. Change in fatigue assessed using Pediatric Quality of Life Multidimensional Fatigue Scale [ Time Frame: Baseline up to 48 weeks post intervention ]
      The PedsQL Multidimensional Fatigue Scale was designed as a generic symptom-specific instrument to measure fatigue in patients with acute and chronic health conditions as well as healthy school and community populations. It has three dimensions, general fatigue, sleep/rest fatigue and cognitive fatigue. Scores range from 0-100 and items are summed and divided by the total to get the mean. Differences between groups and the effects of group assignment on changes over time will be evaluated.

    5. Change in school attendance assessed using parent report [ Time Frame: Baseline up to 48 weeks post intervention ]
      Differences between groups and the effects of group assignment on changes over time will be evaluated.

    6. Markers of cardiometabolic health [ Time Frame: Up to 48 weeks post intervention ]
      Markers of cardiometabolic health include blood pressure, body mass index, waist to height ration, fasting insulin, glucose, and lipid levels. It will be determined if the effect of an interactive web-based physical activity intervention on markers of cardiometabolic health is mediated by changes in fitness among children and adolescents following treatment for acute lymphoblastic leukemia. A causal inference approach will evaluate whether group assignment results in an improved outcome in the presence of a lower PCI. This requires decomposing the averaged total effect into indirect and direct effects of group assignment of on the cardiometabolic outcomes. A principal stratification method will be used that classifies participants into strata based on their performance on the PCI (mediator variable) for each group of the randomized intervention. Mediation analyses would then be based on intent-to-treat effects of group assignment on cardiometabolic health outcome within each strata.

    TRIAL NUMBER: E1910

    Title: A Phase III Randomized Trial of Blinatumomab for Newly Diagnosed BCR-ABL-Negative B Lineage Acute Lymphoblastic Leukemia in Adults

    Purpose: This randomized phase III trial studies combination chemotherapy with blinatumomab to see how well it works compared to induction chemotherapy alone in treating patients with newly diagnosed breakpoint cluster region (BCR)-c-abl oncogene 1, non-receptor tyrosine kinase (ABL)-negative B lineage acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as blinatumomab, may block cancer growth in different ways by targeting certain cells. It is not yet known whether combination chemotherapy is more effective with or without blinatumomab in treating newly diagnosed acute lymphoblastic leukemia.

    TRIAL NUMBER: EA9161

    Title: A RANDOMIZED PHASE III STUDY OF THE ADDITION OF VENETOCLAX TO IBRUTINIB AND OBINUTUZUMAB VERSUS IBRUTINIB AND OBINUTUZUMAB IN UNTREATED YOUNGER PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)

    Purpose: Primary Outcome Measures : Progression-free survival [ Time Frame: Time from randomization to progression or death without documented progression, assessed up to 10 years ] The analysis will be performed using the repeated confidence intervals methodology. At each interim or final analysis, two-sided repeated confidence interval will be constructed using the partial likelihood estimate from stratified Cox proportional hazards model and the critical value based on the Lan-DeMets error-spending function that corresponds to the truncated O'brien-Fleming boundaries.

    Secondary Outcome Measures : Overall survival [ Time Frame: Time from randomization to death due to any cause, assessed up to 10 years ] A hierarchical testing strategy will be used. The analysis will be performed using the repeated confidence intervals methodology. At each interim or final analysis, two-sided repeated confidence interval will be constructed using the partial likelihood estimate from stratified Cox proportional hazards model and the critical value based on the Lan-DeMets error-spending function that corresponds to the truncated O'brien-Fleming boundaries.
    Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events version 5.0 [ Time Frame: Up to 10 years ]
    Other Outcome Measures: Quality of life (QOL) assessed using Functional Assessment of Cancer Therapy-General (FACT-G) and the leukemia sub-scale [ Time Frame: Baseline up to 10 years ] Linear mixed effects models will be used to perform repeated measures regression analysis. Will compare treatment toxicity-related QOL between the two arms. The entire FACT-Leukemia instrument (FACT-G and the leukemia subscale) at baseline will be analyzed using descriptive statistics to assess the impact of chronic lymphocytic leukemia on QOL independent of treatment.
    FACT-Leu Trial Outcome Index (TOI) score over time [ Time Frame: Baseline up to 10 years ] Will use linear mixed effects models will be used to perform repeated measures regression analysis to examine the treatment effect and time effect on FACT-Leu TOI score.
    Adherence defined as patients taking 80% or more of their prescribed doses [ Time Frame: Baseline up to 10 years ] The ASK-12 Survey will be used to measure the likelihood that a patient will take prescribed medications for patients on both arms at baseline and on day 1 +/- 4 days of the following cycles 3, 7, 15, at the time of response evaluation (end of cycle 19), every 6 months for 2 years post response evaluation, at 48 months after randomization, and at time of disease progression. Descriptive statistics will be used to summarize trend in adherence to prescription.

    TRIAL NUMBER: AHEP1531

    Title: Pediatric Hepatic Malignancy International Therapeutic Trial (PHITT)

    Purpose: Primary Outcome Measures : Event-free survival (EFS) [ Time Frame: From date of randomization until progression of existing disease or occurrence of disease at new sites, death from any cause prior to disease progression, or diagnosis of a second malignant neoplasm, assessed up to 5 years ] Descriptive analysis for each non-randomized and randomized question (by treatment arm and overall) will include: the number (and proportion) of each failure event and in total, survival curves will be estimated by the method of Kaplan-Meier, EFS estimates at 3 and 5 years with 95% confidence intervals (CI), median EFS with CI will be reported if appropriate. A Cox proportional hazards model with EFS as an outcome measure and treatment and stratification factors as covariates will be constructed. This model will be used in the context of a Bayesian analysis and a log Hazard Ratio (HR) will be derived. Bayesian Normal-Normal conjugate analysis of the data will be used to compare treatments. The analysis will use non-informative prior to represent no information about prior beliefs regarding relative treatment difference.
    Response in hepatocellular carcinoma (HCC), defined as complete (CR) or partial (PR) response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria [ Time Frame: Up to 5 years ] The main analysis will be based on a log-binomial model for a Bernoulli response variable. This model will be used in the context of a Bayesian analysis. A non-informative null centered proper prior distributions for the parameters will be used. Response rate (RR) and 95% credible interval (CrI) will be presented. Posterior probabilities for the pre-specified values of interest will be provided. Additionally, the posterior probabilities of RR being larger than 0.7, 0.8, 0.9, 1, 1.1, 1.2 and 1.3 will be also provided.

    Secondary Outcome Measures : Failure free survival [ Time Frame: From date of randomization until the date of first documented progression, date of death from any cause, diagnosis of a second malignant neoplasm or failure to go to resection, whichever came first, assessed up to 5 years ] Descriptive analysis for each non-randomized and randomized question (by treatment arm and overall) will include: the number (and proportion) of each failure event and in total, survival curves will be estimated by the method of Kaplan-Meier. Bayesian Normal-Normal conjugate analysis of the data will be used to compare treatments. The analysis will use non-informative prior to represent no information about prior beliefs regarding relative treatment difference.
    Overall survival [ Time Frame: From date of randomization (or registration for non-randomized patients) until the date of death from any cause, assessed up to 5 years ] Incidence of adverse events [ Time Frame: Up to 5 years ] Will be categorized and graded using Common Terminology Criteria for Adverse Events (CTCAE).
    Chemotherapy-related cardiac, nephro- and oto-toxicity [ Time Frame: Up to 5 years ] Will be recorded in relation to each cycle of treatment and will be categorized and graded using Common Terminology Criteria for Adverse Events.
    Hearing loss measured according to the SIOP Boston Scale for oto-toxicity [ Time Frame: Up to 5 years ] Descriptive analysis for each non-randomized and randomized question (by treatment arm and overall) will include: the number (and proportion) of patients at each the SIOP Boston Scale for oto-toxicity category (i.e. grade 0 to grade 4) and the number (and proportion) of patients who are not assessable for this outcome, (i.e. because of early stopping of treatment, additional treatments to protocol treatment, progression prior to the response assessment or death). The number (and proportion) of patients experiencing any grade hearing loss. Grades 1 to grade 4 will be combined in this analysis. The above will be presented for each assessment time point (EOT and at least 1 year and 2 years of follow up).
    Best response defined as compete response (CR) or partial response (PR) based on radiological response (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) and AFP decline [ Time Frame: Up to 5 years ] Descriptive analysis for each non-randomized and randomized question (by treatment arm and overall) will include: best response will be calculated by taking best RECIST category (i.e. CR, PR, stable disease [SD], progressive disease [PD]) for each patient. CR and PR patients will then be grouped into responders. The number (and proportion) of patients at each best response RECIST category (i.e. CR, PR, SD, PD) and the number (and proportion) of patients who are not assessable for response, e.g. because of early stopping of treatment, progression prior to the response assessment or death. The number (and proportion) of responders (CR and PR) and non-responders.
    Surgical resectability defined as complete resection, partial resection or transplant following randomization (or enrollment for non-randomized patients) [ Time Frame: Up to 5 years ] Descriptive analysis for each non-randomized and randomized question (by treatment arm and overall) will include: The number (and proportion) of patients undergoing complete resection, partial resection or transplant. Time to complete resection, partial resection or transplant following randomization (or enrollment for non-randomized patients) will be analyzed using the Kaplan-Meier method.
    Adherence to surgical guidelines defined as the local clinician?s surgical decision to resect or not compared to the current SIOPEL surgical guidelines [ Time Frame: Up to 5 years ] Descriptive analysis for each non-randomized and randomized question (by treatment arm and overall) will include: The number (and proportion) of patients at each combination of SIOPEL surgical guideline (to resect or not) and local clinician?s surgical decision. The degree of agreement will be measured by Cohen?s kappa with CI.

    TRIAL NUMBER: R1112

    Title: RANDOMIZED PHASE III STUDY OF SORAFENIB VERSUS STEREOTACTIC BODY RADIATION THERAPY FOLLOWED BY SORAFENIB IN HEPATOCELLULAR CARCINOMA

    Purpose: PRIMARY OBJECTIVES:
    I. To determine if stereotactic body radiation therapy (SBRT) improves overall survival in hepatocellular carcinoma (HCC) patients treated with sorafenib (sorafenib tosylate).
    SECONDARY OBJECTIVES:
    I. To determine the difference in time to progression (TTP) and progression- free survival (PFS) in HCC patients treated with sorafenib compared to SBRT followed by sorafenib.
    II. To measure differences in toxicity in HCC patients treated with sorafenib versus SBRT followed by sorafenib.
    III. To measure vascular thrombosis response post sorafenib versus SBRT followed by sorafenib.
    IV. To measure differences in health related quality of life (QOL) and quality- adjusted survival in HCC patients treated with sorafenib compared to SBRT followed by sorafenib.
    V. Collection of biospecimens for future correlative studies to investigate differences in potential biomarkers in patients treated with sorafenib versus SBRT followed by sorafenib.
    OUTLINE: Patients are randomized to 1 of 2 treatment arms.
    ARM 1: Patients receive sorafenib tosylate orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.
    ARM 2: Patients undergo SBRT every 24-72 hours for a total of 5 fractions over 5 to 15 days. Within 1-5 days post-SBRT, patients receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.
    Patients are followed weekly during SBRT, monthly during sorafenib tosylate and on the following schedule as a whole from study entry: every 3 months for 3 years, then every 6 months for 2 years and then annually.

    TRIAL NUMBER: A151216

    Title: Genetic Testing For Patients with Resectable or Resected Lung Cancer: Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST)

    Purpose: PRIMARY OBJECTIVES:
    I. To centrally genotype resected lung adenocarcinomas for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements to facilitate accrual to randomized adjuvant studies.
    II. To obtain clinically annotated tumor tissue and patient-matched non-malignant deoxyribonucleic acid (DNA) from peripheral blood, as well as detailed epidemiologic and clinical follow-up data, to allow clinically annotated advanced genomic analyses in concert with the National Cancer Institute (NCI) Center for Cancer Genomics (CCG).
    SECONDARY OBJECTIVES:
    I. To characterize the natural history of EGFR and ALK wild-type lung cancers to allow subsequent development of targeted therapies against genotype-defined sub-populations in the adjuvant and recurrent settings.
    II. To cross-validate local genotyping assays for EGFR and ALK with a central reference standard.
    TERTIARY OBJECTIVES:
    I. To study the genomic evolution of lung cancers by comparing genomic characteristics at resection and at recurrence.
    OUTLINE:
    Patients undergo collection of blood and tissue samples for EGFR and ALK testing via direct sequencing and fluorescence in situ hybridization (FISH). Patients that have had surgery prior to pre-registration will submit samples from the previous surgery for testing.
    After completion of study, patients that are not enrolled on either A081105 or E4512 are followed up every 6 months for 5 years.

    TRIAL NUMBER: E4512

    Title: A Phase III Double-Blind Trial for Surgically Resected Early Stage Non-Small Cell Lung Cancer: Crizotinib versus Placebo for Patients with Tumors Harboring the Anaplastic Lymphoma Kinase (ALK) Fusion Protein

    Purpose: PRIMARY OBJECTIVES:
    I. To evaluate whether adjuvant therapy with crizotinib will result in improved overall survival (OS) over placebo for patients with stage IB >= 4 cm, II and IIIA, anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) following surgical resection.
    SECONDARY OBJECTIVES:
    I. To evaluate and compare disease-free survival (DFS) associated with crizotinib and placebo.
    II. To evaluate the safety profile of crizotinib when given in the adjuvant therapy setting.
    III. To collect tumor tissue and blood specimens for future research.
    OUTLINE: Patients are randomized to 1 of 2 treatment arms.
    ARM A: Patients receive crizotinib orally (PO) twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
    ARM B: Patients receive placebo PO BID on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
    After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly for 5 years.

    TRIAL NUMBER: EA5163

    Title: EA5163/S1709 INSIGNA : A Randomized, Phase III Study of Firstline Immunotherapy Alone or in Combination with Chemotherapy in Induction/Maintenance or Postprogression in Advanced Nonsquamous Non-Small Cell Lung Cancer (NSCLC) with Immunobiomarker SIGNature-Driven Analysis

    Purpose: Primary Outcome Measures : Overall survival (OS) [ Time Frame: From randomization to death from any cause, assessed up to 5 years post treatment ] OS distributions will be estimated using the Kaplan-Meier method.

    Secondary Outcome Measures : Progression-free survival (PFS) [ Time Frame: From randomization to documented disease progression or death from any cause, assessed up to 5 years post treatment ] PFS distributions will be estimated using the Kaplan-Meier method.
    Best objective response [ Time Frame: Up to 5 years post treatment ] Best objective response will be evaluated via Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
    Incidence of adverse events [ Time Frame: Up to 30 days post treatment ] Toxicities will be reported via the Common Terminology Criteria for Adverse Events (CTCAE) criteria version 5.0. Toxicity rates between arms in the overall population will be compared using Fisher's exact tests with a one-sided type I error rate of 1.25%; multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes.
    PD-L1 positivity [ Time Frame: At baseline ] PD-L1 positivity will be defined as >= 1% Tumor Proportion Score (TPS) for the purpose of enrollment onto the trial. Strongly PD-L1 positive is defined as >= 50% TPS; weakly positive is defined as 1% - 49% TPS.

    TRIAL NUMBER: LungMAP

    Title: LungMAP: A MASTER PROTOCOL TO EVALUATE BIOMARKER-DRIVEN THERAPIES AND IMMUNOTHERAPIES IN PREVIOUSLY-TREATED NON-SMALL CELL LUNG CANCER (Lung-MAP Screening Study)

    Purpose: 1.1 Primary Objective of the Master Protocol (LungMAP) The primary objective of this screening study is to test patient specimens to determine eligibility for participation in the biomarker-driven and non-matched sub-studies included within the Lung-MAP umbrella protocol. 1.2 Secondary Objectives a. Screening Success Rate Objective To evaluate the screen success rate defined as the percentage of screened patients that register for a therapeutic sub-study. Screen success rates will be evaluated for the total screened population and by the subset of patients screened following progression on previous therapy or pre-screened on current therapy. b. Translational Medicine Objectives 1. To evaluate circulating tumor DNA (ctDNA) and compare to the FMI Foundation tissue molecular profiling results in patients who submit a new biopsy for screening. 2. To establish a tissue/blood repository

    TRIAL NUMBER: NRG-LU005

    Title: Limited Stage Small Cell Lung Cancer (LS-SCLC): A Phase II/III Randomized Study of Chemoradiation Versus Chemoradiation Plus Atezolizumab

    Purpose: Primary Outcome Measures :
    Progression-free survival (PFS) (Phase II) [ Time Frame: Time from randomization to any documented progression or death due to any cause, whichever occurs first, assessed up to 5 years ] Progressive disease (PD) will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will compare the distributions of PFS between treatment arms using a one-sided stratified log-rank test in all randomized eligible patients. The rates at various timepoints (e.g., every 6 months after randomization) and medians of PFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95% confidence interval (CI) will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Results from an unstratified analysis will also be provided.
    Overall survival (OS) (Phase III) [ Time Frame: Time from randomization to the date of death due to any cause, assessed up to 5 years ] The primary hypotheses for the phase II and III portions will be evaluated by comparing arm 1 to arm 2 based on PFS (phase II) and OS (phase III) using a stratified log-rank test. Hazard ratios will be estimated using a stratified Cox regression model. Event rates over time will be estimated within each treatment group using the Kaplan-Meier method.

    Secondary Outcome Measures :
    PFS (phase III) [ Time Frame: Time from randomization to any documented progression or death due to any cause, whichever occurs first, assessed up to 5 years ] The primary hypotheses for the phase II and III portions will be evaluated by comparing arm 1 to arm 2 based on PFS (phase II) and OS (phase III) using a stratified log-rank test. Hazard ratios will be estimated using a stratified Cox regression model. Event rates over time will be estimated within each treatment group using the Kaplan-Meier method.
    Incidence of adverse events [ Time Frame: Up to 5 years ] For each patient, the maximum severity reported for both immune mediated and non-immune mediated adverse events will be used in the summaries. Adverse events will be summarized regardless of relationship to protocol treatment as assessed by the investigator. All adverse events, adverse events leading to withdrawal, interruption or modification of protocol treatment, Grade >= 3 adverse events, and serious adverse events will be summarized. Deaths and cause of death will be summarized. The rate of treatment-related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE, v.5.0) will be reported with the frequency and severity (e.g., type, grade, and attribution) by arm, the analysis will be performed at the time of both phase II and phase III (if applicable) primary endpoint analyses. All adverse events will be classified as either immune or non-immune mediated.
    Objective response rate (ORR) [ Time Frame: Up to 5 years ] Will be defined as the proportion of all randomized subjects whose best overall response (BOR) is either a complete response (CR) or partial response (PR) per RECIST 1.1 criteria. ORR will be compared using a two-sided 5% level Cochran-Mantel Haenszel (CMH) test stratified by the same stratification factors used for randomization. An associated odds ratio and 95% CI will be calculated. The ORR and its corresponding 95% exact CI will also be calculated by Clopper-Pearson for each treatment arm. The difference in ORR between the two treatment arms along with the two-sided 95% CI will be estimated using the following CMH method of weighting, adjusting for the stratification factors.
    Local control [ Time Frame: Up to 5 years ] Will be defined as freedom from local progression, in which a failure is defined as intrathoracic tumor progression by RECIST 1.1 criteria. Local control will be analyzed as competing risks data based on cause-specific hazards approaches, where deaths without local failure will be considered as a competing event and analyzed as "censoring" of local failure. The rates at various timepoints (e.g., every 6 months after randomization) and medians of PFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95% CI will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Results from an unstratified analysis will also be provided.
    Distant metastases-free survival (DMFS) [ Time Frame: Time between the date of randomization and the first date of documented distant metastases or death due to any cause, whichever occurs first, assessed up to 5 years ] Will compare the distributions of DMFS between treatment arms using a one-sided stratified log-rank test in all randomized eligible patients. The rates at various timepoints (e.g., every 6 months after randomization) and medians of DMFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95% CI will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Results from an unstratified analysis will also be provided.
    Quality of life (QoL) [ Time Frame: Up to 15 months after the end of the 4th cycle of chemotherapy ] Will be measured by the Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI). Fisher's exact test will be used to compare the proportions of patients experiencing clinically meaningful deterioration (CMD) between the two arms. FACT-TOI deterioration rates and associated 95% confidence interval will be calculated for each treatment group, based on all randomized subjects. Clopper-Pearson method will be used for calculating 95% CI. The deterioration rates of each arm will also be compared using the CMH test, stratified by histology. FACT-TOI at baseline and at each subsequent assessment, as well as their change from baseline will be summarized using descriptive statistics by treatment group as randomized. The scores at baseline and subsequent time points, as well the changes from baseline at each time point for each treatment group will be compared using the two-sample t-test.
    Quality-adjusted survival [ Time Frame: Up to 2 years ] Assessed using score from the 5-level EuroQol 5-dimensional questionnaire (EQ-5D-5L). Defined as the weighted sum of different time episodes added up to a total quality-adjusted life-year. Subjects' overall health state on a visual analog scale (VAS) at each assessment time point will be summarized using descriptive statistics by treatment group, as randomized. Proportion of subjects reporting problems for the five EQ-5D-5L dimensions at each assessment time point will be summarized by level of problem and by treatment group, as randomized. Percentages will be based on number subjects assessed at assessment time point. Subjects' overall health state on a visual analog scale (EQ-VAS) at each assessment time point will be summarized using descriptive statistics by treatment group, as randomized. Proportion of subjects reporting problems for the five EQ-5D dimensions at each assessment time point will be summarized by level of problem and by treatment group, as randomized.
    Level of fatigue [ Time Frame: Up to 2 years ] Will be measured by the Patient-Reported Outcomes Measurement Information System (PROMIS). Baseline and PROMIS at each subsequent assessment, as well as their change from baseline will be summarized using descriptive statistics by treatment group as randomized. The change from baseline to subsequent timepoints may be compared between treatment arms using a t-test, or Wilcoxon test if the data is non-normal.
    Blood based tumor mutational burden (bTMB) and tissue-based tumor mutational burden (tTMB) [ Time Frame: Up to 5 years ] Correlation with clinical outcomes will be done by summarizing the statistical power to detect interaction effects (ratio of hazard ratios) of 0.33 when the marker positive prevalence is 20%, at 2-sided significance level of 0.05.

    Other Outcome Measures:
    Patient-reported symptomatic toxicities [ Time Frame: Up to 15 months after completion of chemoradiation therapy ] Will be measured by Patient Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE). For each symptom and each domain (i.e., frequency, severity, and interference), counts and frequencies will be summarized for the worst score experienced by the patient by treatment arm.

    TRIAL NUMBER: S1800A

    Title: Ramucirumab and Pembrolizumab Versus Standard of Care in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer (A Lung-MAP Non-Match Treatment Trial)

    Purpose: This phase II Lung-MAP non-Match treatment trial studies how well ramucirumab and pembrolizumab work versus standard of care in treating patients with non-small cell lung cancer that is stage IV or has come back. Immunotherapy with monoclonal antibodies, such as ramucirumab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in standard of care chemotherapy for non-small cell lung cancer, such as docetaxel, gemcitabine hydrochloride, and pemetrexed, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ramucirumab and pembrolizumab together may work better in treating patients with non-small lung cancer compared to standard of care.

    TRIAL NUMBER: AALL1731

    Title: A Phase 3 Trial Investigating Blinatumomab (IND# 117467, NSC# 765986) in Combination with Chemotherapy in Patients with Newly Diagnosed Standard Risk or Down syndrome B-Lymphoblastic Leukemia (B-ALL) and the Treatment of Patients with Localized B-Lymphoblastic Lymphoma (B-LLy)

    Purpose:

    Primary Outcome Measures :
    1. Post-Consolidation disease free survival (DFS) with addition of 2 cycle of blinatumomab in patients with standard risk (SR) B-lymphoblastic leukemia (B-ALL) and higher risk features, and patients with standard risk average (SR-Avg) B-ALL [ Time Frame: 5 years ]
      Efficacy design and standard survival analysis methods used to detect improvement in post-Consolidation DFS due to the addition of 2 cycles of blinatumomab to standard therapy in patients with SR B-ALL and higher risk features, and patients with SR-Avg B-ALL who are negative for minimal residual disease (MRD) by flow cytometry but have detectable or indeterminate MRD as measured by high-throughput sequencing (HTS) at end of induction (EOI), and patients with double trisomy of chromosomes 4 and 10 (DT) with MRD (flow) 0.01% - <0.1%.

    2. DFS in boys in the SR-favorable subset of SR B-ALL [ Time Frame: 5 years ]
      Time from end of consolidation to first event (relapse, second malignant neoplasm, remission, death) or censored at date of last contact for those who are disease-free.


    Secondary Outcome Measures :
    1. DFS for patients with SR-Avg B-ALL who are negative for MRD measured by flow cytometry and HTS at EOI when treated with standard chemotherapy with a treatment duration of 2 years from the start of interim maintenance (IM)1, regardless of sex [ Time Frame: 5 years ]
      Time from end of consolidation to first event (relapse, second malignant neoplasm, remission, death) or censored at date of last contact for those who are disease-free.

    2. DFS for patients with standard-risk favorable (SR-Fav) B-ALL [ Time Frame: 5 years ]
      Time from end of consolidation to first event (relapse, second malignant neoplasm, remission, death) or censored at date of last contact for those who are disease-free.

    3. Treatment-related mortality in Down syndrome high risk (DS-high) patients after replacement of intensive elements of standard chemotherapy (omission of anthracyclines in induction, omission of the second month of DI) with 3 cycles of blinatumomab [ Time Frame: 5 years ]
    4. DFS of DS-High B-ALL patients when intensive elements of chemotherapy are replaced with 3 cycles of blinatumomab [ Time Frame: 5 years ]
      Time from end of consolidation to first event (relapse, second malignant neoplasm, remission, death) or censored at date of last contact for those who are disease-free.

    5. DFS of patients with localized B-lymphoblastic lymphoma receiving standard risk acute lymphoblastic leukemia therapy [ Time Frame: 5 years ]
      Time from end of consolidation to first event (relapse, second malignant neoplasm, remission, death) or censored at date of last contact for those who are disease-free.

    6. Neurocognitive functioning [ Time Frame: Baseline to 2 years after IM1 ]
      Compare the change in neurocognitive functioning, as measured by the CogState Cognitive Composite, from baseline to end-of-therapy among patients with ALL ages 4-< 10 years at the time of diagnosis between children from poor families (defined as presence of household material hardship (HMH), including either food, housing or energy insecurity) and non-poor families (absence of HMH).

    7. Caregiver burden and patient/proxy-reported symptoms among those enrolled in HMH [ Time Frame: Baseline to 2 years after IM1 ]
      Compare the demands and work limitations on caregivers of children with ALL receiving chemotherapy versus chemotherapy with the addition of blinatumomab and to compare the change in the demands and work limitations over time, measured by the Care of My Child with Cancer questionnaire and the Caregiver Work Limitations questionnaire during post-Induction therapy. Patient/proxy reported symptoms measured by Memorial Symptom Assessment Scale.


    Other Outcome Measures:
    1. Adaptive and innate immune functions and host genetic factors associated with severe infectious complications in children with DS B-ALL [ Time Frame: 5 years ]
      FlowSom high resolution clustering approach to identify cellular subsets and/or activation states (endophenotypes) that distinguish cases from controls. Conduct a genome-wide assessment using a case-control approach comparing those who develop grade 4-5 microbiologically documented infections (cases) compared to those who do not (controls).

    2. Neurocognitive, functional, and quality of life outcomes in patients with DS and ALL [ Time Frame: 5 years ]
      Measured by caregiver (parent/legal guardian) questionnaires.

    3. Prevalence of minimal marrow disease (MMD) in B-LLy [ Time Frame: 5 years ]
      Correlate MMD at diagnosis with outcome in patients with B-LLy.

    TRIAL NUMBER: S1608

    Title: RANDOMIZED PHASE II TRIAL IN EARLY RELAPSING OR REFRACTORY FOLLICULAR LYMPHOMA

    Purpose: Primary Outcome Measures: Complete response (CR) [ Time Frame: Up to 6 courses ] Will be assessed.

    Secondary Outcome Measures: Duration of response (complete response, partial response) [ Time Frame: Up to 5 years ] Will be calculated using the method of Kaplan-Meier.
    Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 5 years ] Toxicity rates can be estimated to within at least ± 15% with 95% confidence.
    M7-LIPI model validation [ Time Frame: Up to 5 years ] The Cox proportional hazards model will be used to assess the association of the m7-FLIPI with to PFS.
    Non-invasive genotyping and circulating tumor deoxyribonucleic acid (DNA) assessment [ Time Frame: Up to 5 years ] Sensitivity, specificity, positive predictive value, negative predictive value, and kappa coefficient will be used to evaluate the concordance. Will evaluate the association of detection of active lymphoma by positron emission tomography-computed tomography and the detection of circulating tumor DNA in plasma at baseline, after 6 and 12 cycles, and at 30 months after initiation of study therapy. Chi-square test will be used to evaluate the association and odds ratio will be calculated.
    Overall survival [ Time Frame: Up to 5 years ] Will be calculated using the method of Kaplan-Meier. 95% confidence for the survival estimates will be constructed using the method of Brookmeyer-Crowley. With 45 eligible patients in each arm, overall survival (OS) at a particular time point, and the 30-month sustained response rate can be estimated to within at least ± 15% with 95% confidence
    Progression-free survival [ Time Frame: From date of registration to date of first observation of progressive disease, or death due to any cause, assessed up to 5 years ] Will be calculated using the method of Kaplan-Meier. 95% confidence for the survival estimates will be constructed using the method of Brookmeyer-Crowley. With 45 eligible patients in each arm, progression free survival (PFS) at a particular time point, and the 30-month sustained response rate can be estimated to within at least ± 15% with 95% confidence

    Estimated Enrollment: 150 Actual Study Start Date: August 10, 2017 Estimated Study Completion Date: December 31, 2022 Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

    TRIAL NUMBER: EA6134

    Title: A Randomized Phase III Trial of Dabrafenib + Trametinib Followed by Ipilimumab + Nivolumab at Progression vs. Ipilimumab + Nivolumab Followed by Dabrafenib + Trametinib at Progression in Patients With Advanced BRAFV600 Mutant Melanoma

    Purpose: This randomized phase III trial studies how well initial treatment with ipilimumab and nivolumab followed by dabrafenib and trametinib works and compares it to initial treatment with dabrafenib and trametinib followed by ipilimumab and nivolumab in treating patients with stage III-IV melanoma that contains a mutation known as v-raf murine sarcoma viral oncogene homolog B V600 (BRAFV600) and cannot be removed by surgery. Ipilimumab and nivolumab may block tumor growth by targeting certain cells. Dabrafenib and trametinib may block tumor growth by targeting the BRAFV600 gene. It is not yet known whether treating patients with ipilimumab and nivolumab followed by dabrafenib and trametinib is more effective than treatment with dabrafenib and trametinib followed by ipilimumab and nivolumab.

    TRIAL NUMBER: S1801

    Title: A PHASE II RANDOMIZED STUDY OF ADJUVANT VERSUS NEOADJUVANT MK-3475 (PEMBROLIZUMAB) FOR CLINICALLY DETECTABLE STAGE III-IV HIGH RISK MELANOMA

    Purpose: Primary Outcome Measures : Event-free survival (EFS) in patients with high-risk resectable melanoma randomized to neoadjuvant pembrolizumab with patients randomized to adjuvant pembrolizumab [ Time Frame: Date of randomization to date of first progression or death assessed up to 10 years ] We will use exponential-mixture cure models to describe EFS patterns in the arms.

    Secondary Outcome Measures : Overall survival (OS) [ Time Frame: Up to 10 years ] Will be estimated using the Kaplan-Meier method and compared between arms using log-rank tests and Cox regression models.
    Disease control [ Time Frame: At 24 weeks ] Will be estimated using the Kaplan-Meier method and compared between arms using log-rank tests and Cox regression models.
    Local/regional control in the surgical site(s) [ Time Frame: Up to 10 years ] Will be estimated using the Kaplan-Meier method and compared between arms using log-rank tests and Cox regression models.
    Total number of pembrolizumab doses [ Time Frame: Up to 10 years ] Will use Fisher's exact test to compare the number of pembrolizumab doses received by patients on each treatment arm.
    Pathologic response rate [ Time Frame: Up to 10 years ] Will be tabulated for the neoadjuvant arm and exact 95% confidence intervals will be constructed.
    Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 response rate [ Time Frame: Up to 10 years ] Will be tabulated for the neoadjuvant arm and exact 95% confidence intervals will be constructed.
    Immune-related (i)RECIST response rate [ Time Frame: Up to 10 years ] Will be tabulated for the neoadjuvant arm and exact 95% confidence intervals will be constructed.

    TRIAL NUMBER: A031102

    Title: A RANDOMIZED PHASE III TRIAL COMPARING CONVENTIONAL-DOSE CHEMOTHERAPY USING PACLITAXEL, IFOSFAMIDE, AND CISPLATIN (TIP) WITH HIGH-DOSE CHEMOTHERAPY USING MOBILIZING PACLITAXEL PLUS IFOSFAMIDE FOLLOWED BY HIGH-DOSE CARBOPLATIN AND ETOPOSIDE (TI-CE) AS FIRST SALVAGE TREATMENT IN RELAPSED OR REFRACTORY GERM CELL TUMORS

    Purpose: The study is an international collaboration with European sites. Collaborators on the study include the National Cancer Institute, the European Organization for Research and Treatment of Cancer and the Movember Foundation. Randomization will be stratified by region (North America and Europe) and by modified IPFSG (International Prognostic Factor Study Group) risk classification (low, intermediate and high). The primary and secondary objectives are described below.
    Primary Objective:
    1. To compare the overall survival in patients treated with conventional-dose chemotherapy using the TIP regimen with high-dose chemotherapy (HDCT) plus autologous stem cell transplant (ASCT) using the TI-CE regimen as initial salvage treatment of patients with relapsed or refractory germ cell tumors (GCT)
    Secondary Objectives: 1.To compare the progression-free survival (PFS) of patients treated with initial salvage HDCT with TI-CE versus initial salvage CDCT with TIP 2.To compare the favorable response rate (FRR) of patients treated with initial salvage HDCT with TI-CE versus initial salvage CDCT with TIP 3.To compare the toxicity, including treatment-related mortality, associated with high-dose chemotherapy and ASCT using TI-CE compared with conventional-dose chemotherapy using TIP as initial salvage treatment for patients with relapsed or refractory GCT 4.To prospectively evaluate the IPFSG scoring system as a predictor of outcome to initial salvage therapy in patients with relapsed or refractory GCT. In this trial, randomization will be stratified by a modification of their IPFSG category and we will prospectively evaluate whether or not actual outcomes vary by risk group in the appropriate manner (low risk patients have higher OS than high-risk group). 5.To evaluate the association between tumor marker decline rates of Alpha-Fetoprotein (AFP) and Human Chorionic Gonadotropin (HCG) with OS and PFS.
    Treatment is to continue until disease progression, unacceptable toxicity or completion of all protocol treatment.

    TRIAL NUMBER: ABTR04B1

    Title: ESTABLISHING CONTINUOUS CELL LINES AND XENOGRAFTS FROM PEDIATRIC CANCERS FOR BIOLOGICAL AND PRE-CLINICAL THERAPEUTIC STUDIES

    Purpose: OBJECTIVES: ?Establish and bank cell lines and/or xenografts from pediatric patients with cancer. ?Establish continuous cell lines, under carefully controlled conditions, from pediatric patients with cancer. ?Establish transplantable xenografts in immunocompromised mice from tumor cells that are difficult to establish as continuous cell lines in vitro. ?Create a bank of cell lines and generate sufficient vials of cryopreserved cells for distribution to investigators with approved COG biology protocols. ?Characterize cell lines from childhood cancers with respect to DNA short tandem repeat molecular profile as a "fingerprint" of original cell line identity. ?Characterize cell lines for the ability for sustained growth in tissue culture and/or as mouse xenografts. ?Characterize cell lines for mycoplasma contamination. ?Characterize cell lines for expression of molecular makers that confirm the tumor-type of the cell line and the immortal nature of the cells (telomerase) and the expression of molecular markers that may correlate with drug resistance.
    OUTLINE: This is a multicenter study. Specimens are stratified according to disease (acute lymphoblastic leukemia vs acute myeloid leukemia vs lymphoma vs osteogenic sarcoma vs Ewing family of tumors vs rhabdomyosarcoma vs primitive neuroectodermal tumor vs glioma vs astrocytoma vs rhabdoid tumors vs hepatoblastoma vs retinoblastoma vs Wilms tumor vs germ cell tumors vs other diagnoses).
    Leftover tissue from diagnostic procedures and/or surgery is cryopreserved and banked. Blood and/or bone marrow are also collected and banked.
    Cell lines are established and characterized via reverse-transcriptase polymerase chain reaction and/or flow cytometry for biomarkers and by DNA fingerprinting.
    Markers to be identified may include the following: ?Neuroblastoma: tyrosine hydroxylase, protein gene product (PGP) 9.5, GD2, HLA class I, and HSAN 1.2 antigens ?Ewing family of tumors: EWS-FLI1, EWS-ERG, and PGP 9.5 ?Retinoblastoma: interphotoreceptor retinoid-binding protein ?Acute lymphoblastic leukemia: immunophenotype ?Alveolar rhabdomyosarcoma: PAX3-FKHR, PAX7-FKHR, and MyoD1 ?All cell types: telomerase expression including hTR and hTERT Mutations of TP53 gene are detected by flow cytometry and/or immunocytochemistry.
    No results of these tests are provided to the patient, the patient's physician, or the patient's medical records.
    PROJECTED ACCRUAL: A total of 500 specimens per stratum will be accrued for this study.

    TRIAL NUMBER: AGCT1531

    Title: A PHASE 3 STUDY OF ACTIVE SURVEILLANCE FOR LOW RISK AND A RANDOMIZED TRIAL OF CARBOPLATIN VS. CISPLATIN FOR STANDARD RISK PEDIATRIC AND ADULT PATIENTS WITH GERM CELL TUMORS

    Purpose: Primary Outcome Measures:
    EFS [ Time Frame: The time from study entry to the date of death, date of disease progression or recurrence, date of second malignant neoplasm or date of last contact and ascertained as alive, whichever comes first, assessed up to 5 years ] Overall survival (OS) [ Time Frame: The time from randomization to date of date of death or date of last follow-up and ascertained as alive, assessed up to 8 years ] A 1-sided lower 85% confidence limit for the 2-year survival will be constructed, and if this confidence limit is greater than 0.95, it will be concluded that the strategy provides sufficient OS.

    Secondary Outcome Measures:
    Content validity and understandability of AYA-Hearing Screen assessed by questionnaire [ Time Frame: Baseline ] Incidence of ototoxicity [ Time Frame: 4 weeks after the last dose of platin therapy ] Will compare the proportion of patients who demonstrate hearing loss according to the International Society of Pediatric Oncology criteria.
    Novel genetic variants associated with an increased risk of platinum-associated ototoxicity as determined by standard audiology [ Time Frame: Up to 10 years ] For each candidate gene, will perform an exact two-sided test for the equality of binomial proportions for the event - patient has the candidate gene. The two groups compared will be defined by the presence of SHL. Will use the Bonferroni correction to control experiment-wise error and designate the result as significant if the observed p-value is less than or equal to 0.0025.
    Utility of the 4-miRNA panel as markers diagnostic of MGCTs [ Time Frame: Up to 10 years ] Will use categorical data methods and estimate the probability of demonstrating an elevated miRNA value as the proportion of patients who have the particular miRNA elevated.
    Utility of the 4-miRNA panel as markers diagnostic of MGCTs [ Time Frame: Up to 10 years ] Will compare the diagnostic sensitivity of serum markers, particularly elevated alpha-fetoprotein, to that of elevated microRNA for each of the microRNAs, as well as the characteristic any microRNA elevated. Will perform McNemar's test. The result for each serum evaluation (elevated or not elevated) for each sample on which both serum marker and microRNA evaluation are obtained will be cross tabulated and the p-value associated with McNemar's test calculated. A p-value of 0.05 or less will be considered evidence of differential sensitivity.

    Other Outcome Measures:
    Activation of protein signaling pathway [ Time Frame: Up to 10 years ] Will assess the relationship between pathway activation, including EGFR, MAP Kinase and P3K and risk for disease progression. Tumor materials will be evaluated for the activation of specific pathways, including the three mentioned above. The effect of pathway activation, coded as yes vs. no, on the cause-specific hazard of EFS component disease progression will be estimated by relative risk regression considering other EFS events as censoring events. Will use the Benjamini and Hochberg procedure to control the false discovery rate.
    Binomial data [ Time Frame: Up to 10 years ] Will use repeated measures binomial data as the initial approach to investigating this exploratory aim. Each biomarker will be examined individually. The predictor variables will be the measured value of particular novel biomarker and randomized treatment regimen. The response variable will be the occurrence of grade 3 or higher nephrotoxicity during the next treatment cycle. Will use logistic regression with a shared random frailty for outcomes for the same individual, when the subject's biomarkers are evaluated more than once during protocol therapy and the particular toxicity type is revers
    Incidence of kidney dysfunction [ Time Frame: 12-16 weeks after the last dose of platin therapy ] Two patient characteristics will be used to measure kidney dysfunction: (1) the presence of Grade 1 or greater elevation of serum creatinine; and a second measure that is more sensitive for damage to the renal endothelium (2) albuminuria.
    Incidence of self-reported peripheral neuropathy assessed by the 11-item Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity scale [ Time Frame: Up to 12 months ] Will compare the characteristics obtained at the start of chemotherapy of patients from the relevant groups who contribute to the patient reported outcome analyses with those who do not to investigate whether the measured group may not be representative of the study population. Will also conduct other sensitivity analysis as appropriate to assess the effects of missing data on the analysis for this aim.
    Incidence of self-reported peripheral neuropathy assessed by the 11-item Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity scale [ Time Frame: Up to 12 months ] Will compare self-reported peripheral neuropathy and other patient-reported outcomes between children, adolescents and young adults with standard risk germ cell tumors treated with carboplatin-based chemotherapy as compared to cisplatin based chemotherapy.
    Prognostic effects of the marker defined by microRNA signature present or high values of alpha-fetoprotein or beta-HCG [ Time Frame: Up to 10 years ] Will be assessed using a proportional approach. EFS from time of enrollment will be used for markers that are obtained at enrollment. EFS post complete evaluation of marker decline will be used for markers where the characteristic is the change in a putative marker.
    Prognostic significance of the 4-miRNA panel [ Time Frame: Up to 10 years ] Will be assessed using time-dependent covariate analysis.

    TRIAL NUMBER: AGCT1532

    Title: Phase 3 Accelerated BEP Trial: A randomised phase 3 trial of accelerated versus standard BEP chemotherapy for patients with intermediate and poor-risk metastatic germ cell tumours

    Purpose: The purpose of this study is to determine whether accelerated BEP chemotherapy is more effective than standard BEP chemotherapy in males with intermediate and poor-risk metastatic germ cell tumours.
    Bleomycin, Etoposide, Cisplatin (BEP) administered 3-weekly x 4 remains standard 1st line chemotherapy for intermediate- and poor-risk metastatic germ cell tumours (GCTs). Cure rates are over 90% for good-risk disease, 85% with intermediate-risk, and about 70% for poor-risk disease. Previous strategies to improve first-line chemotherapy have failed to improve cure rates and were more toxic than BEP. New strategies are needed for patients with intermediate and poor-risk disease. BEP is accelerated by cycling Cisplatin and etoposide 2-weekly instead of 3-weekly. The Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) is conducting a trial comparing accelerated BEP with standard BEP. The aim of this study is to determine if accelerated BEP is superior to standard BEP as first-line chemotherapy for intermediate and poor risk metastatic GCTs.

    TRIAL NUMBER: ALTE05N1

    Title: Umbrella Long-Term Follow-Up Protocol

    Purpose: OBJECTIVES:
    ?To develop a mechanism for tracking and retaining patients enrolled on COG protocols. ?To maintain regular, lifetime contact with patients in order to obtain current identification and contact information, and self/parent-reported health status. ?To locate patients who are lost-to-follow-up for COG (or Legacy Group) protocols targeted for follow-up by the Long-Term Follow-Up Center (LTFC). ?To provide current patient contact information and self/parent-reported health status updates to the COG Statistics and Data Center (SDC) and to each patient's COG institution. ?To facilitate collection of protocol-specific outcome data through collaboration with the COG Late Effects Committee, the SDC, and the member institutions. ?To collect cumulative therapeutic exposure data (via therapeutic summaries completed online by treating institutions) on patients completing active therapy. OUTLINE: This is an umbrella protocol for all long-term follow-up at COG institutions. Approximately 6 months after completion of therapy patients receive a mailed packet introducing the Long-Term Follow-Up Center (LTFC) and containing information related to their individualized, protocol-specific follow-up guidelines. Patients are asked to complete a patient response form, verify information provided in packet, update contact information, and complete a Health Status Update Form. The Health Status Update Form is a brief document including questions about current health status, disease status, and cancer therapy received since the last mailing. Patients receive protocol-specific automatic reminders, and may respond by use of postage prepaid envelopes, email, or 24-hour toll-free telephone.

    TRIAL NUMBER: APEC1621A

    Title: Pediatric MATCH: Trk Inhibitor LOXO-101 in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions

    Purpose: This phase II trial studies Trk inhibitor LOXO-101 in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with NTRK fusions that have spread to other places in the body and have come back or do not respond to treatment. Trk inhibitor LOXO-101 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth

    TRIAL NUMBER: APEC1621B

    Title: Pediatric MATCH: Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations

    Purpose: This phase II trial studies how well erdafitinib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders that have spread to other places in the body and have come back or do not respond to treatment with FGFR mutations. Erdafitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621C

    Title: Pediatric MATCH: Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations

    Purpose: This phase II trial studies how well tazemetostat works in treating patients with solid tumors, non-hodgkin lymphoma, or histiocytic disorders that have spread to other places in the body and have come back or do not respond to treatment and have EZH2, SMARCB1, or SMARCA4 gene mutations. Tazemetostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621D

    Title: Pediatric MATCH: PI3K/mTOR Inhibitor LY3023414 in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations

    Purpose: This phase II trial studies how well PI3K/mTOR inhibitor LY3023414 works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with TSC or PI3K/MTOR mutations that have spread to other places in the body and have come back or do not respond to treatment. PI3K/mTOR inhibitor LY3023414 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621E

    Title: Pediatric MATCH: Selumetinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating MAPK Pathway Mutations

    Purpose: This phase II trial studies how well selumetinib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with MAPK pathway activation mutations that have spread to other places in the body and have come back or do not respond to treatment. Selumetinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621F

    Title: Pediatric MATCH: Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations

    Purpose: This phase II trial studies how well ensartinib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with ALK or ROS1 genomic alterations that have come back or do not respond to treatment and have spread to other places in the body. Ensartinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621G

    Title: Pediatric MATCH: Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations

    Purpose: This phase II trial studies how well vemurafenib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with BRAF V600 mutations that have spread to other places in the body and have come back or do not respond to treatment. Vemurafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621H

    Title: Pediatric MATCH: Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes

    Purpose: This phase II trial studies how well olaparib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with defects in deoxyribonucleic acid (DNA) damage repair genes that have spread to other places in the body and have come back or do not respond to treatment. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621SC

    Title: Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders

    Purpose: This screening and multi-sub-study phase II trial studies how well treatment that is directed by genetic testing works in pediatric patients with solid tumors, non-Hodgkin lymphomas, or histiocytic disorders that have progressed following at least one line of standard systemic therapy and/or for which no standard treatment exists that has been shown to prolong survival. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic changes or abnormalities (mutations) may benefit more from treatment which targets their tumor's particular genetic mutation, and may help doctors plan better treatment for patients with solid tumors or non-Hodgkin lymphomas.

    TRIAL NUMBER: EAY131

    Title: EAY131: Molecular Analysis for Therapy Choice (NCI-MATCH)

    Purpose: This phase II trial studies how well treatment that is directed by genetic testing works in patients with solid tumors or lymphomas that have progressed following at least one line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment which targets their tumor's particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors or lymphomas.

    TRIAL NUMBER: S1609

    Title: SWOG 1609: DART: Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors Treatment with Ipilimumab and Nivolumab for Rare Cancers

    Purpose: Both Ipilimumab and Nivolumab have already been FDA-approved to treat other cancers. However, Ipilimumab and Nivolumab are investigational and not FDA-approved for use in combination in treating rare cancers or cancers of unknown primary origin.

    TRIAL NUMBER: EAA173

    Title: DARATUMUMAB TO ENHANCE THERAPEUTIC EFFECTIVENESS OF REVLIMID IN SMOLDERING MYELOMA (DETER-SMM)

    Purpose: Primary Outcome Measures :
    Overall survival (OS) [ Time Frame: From randomization to death due to any cause, or censored at date last known alive, assessed up to 15 years ] Will be estimated using the Kaplan-Meier (KM) method and compared using a stratified log-rank test. Stratified cox proportional hazards regression will produce a treatment hazard ratio estimate.
    Functional Assessment of Cancer Therapy-General (FACT-G) score [ Time Frame: Baseline to 24 cycles of treatment (each cycle is 28 days) ] A general effect size measure of half standard deviation will be used to establish the minimally important difference. Descriptive statistics (mean, standard deviation [SD], median, range) will be used to evaluate the distribution of levels and changes for the set of health-related quality of life (QOL) evaluations. Levels and changes will also be assessed graphically. Changes from baseline will be analyzed using linear mixed models based on restricted maximum likelihood estimation with covariance matrix maximizing Akaike information criteria. Models with treatment, assessment time, and treatment by assessment time interaction with and without other predictors will be fit. If there is substantial missingness, will analyze the data according to the methods described in Schluchter and Schluchter, Greene and Beck.

    Secondary Outcome Measures :
    Progression-free survival (PFS) [ Time Frame: From randomization until disease progression or death due to any cause, or censored at date of last disease evaluation, assessed up to 15 years ] Will be estimated using the KM method and compared using a stratified log-rank test. Stratified cox proportional hazards regression will produce a treatment hazard ratio estimate.
    Best response on treatment based on International Myeloma Working Group (IMWG) criteria [ Time Frame: At 12 and 24 months ] Response will be tabulated by category. Response rates of very good partial response (VGPR) or better and partial response (PR) or better will be compared using the Fisher's exact test. Ineligible patients are excluded from the analysis and unevaluable patients are counted in the denominator.
    Incidence of adverse events by worst grade and type for treated patients determined using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: Up to 28 days post-treatment ] Will monitor the toxicities experienced by all treated patients. Will compare rates of worst grade 3 or higher non-hematologic treatment-related events using the Fisher's exact test.
    Incidence of grade 3 or higher infusion-related reactions over course 1 determined based on CTCAE [ Time Frame: During cycle 1 of treatment (each cycle is 28 days) ] Will monitor the toxicities experienced by all treated patients. Will compare rates of worst grade 3 or higher non-hematologic treatment-related events using the Fisher's exact test.
    Stem cell (SC) mobilization failure [ Time Frame: After 4 to 6 cycles of treatment (each cycle is 28 days) ] Defined as not collecting a minimum of 5x10^6 CD34 cells per kilogram weight. SC mobilization and type of growth factor support will be summarized overall and by treatment arm with descriptive statistics.
    Early SC mobilization feasibility [ Time Frame: Up to 6 cycles of treatment (each cycle is 28 days) ] Defined as the proportion of patients less than 65 years of age treated for 6 courses who opt for SC mobilization. SC mobilization and type of growth factor support will be summarized overall and by treatment arm with descriptive statistics.
    Type of growth factor support [ Time Frame: During 4 to 6 cycles of treatment (each cycle is 28 days) ] SC mobilization and type of growth factor support will be summarized overall and by treatment arm with descriptive statistics.
    Change in FACT-G score [ Time Frame: From treatment end to 6 months post-treatment ] A general effect size measure of half standard deviation will be used to establish the minimally important difference. Descriptive statistics (mean, SD, median, range) will be used to evaluate the distribution of levels and changes for the set of health-related QOL evaluations. Levels and changes will also be assessed graphically. Changes from baseline will be analyzed using linear mixed models based on restricted maximum likelihood estimation with covariance matrix maximizing Akaike information criteria. Models with treatment, assessment time, and treatment by assessment time interaction with and without other predictors will be fit. If there is substantial missingness, will analyze the data according to the methods described in Schluchter and Schluchter, Greene and Beck.
    Levels of FACT-G score at each assessment time point [ Time Frame: From baseline, at 3, f7, 13, 19 cycles of treatment, and early discontinuation of treatment, assessed up to 24 cycles of treatment (each cycle is 28 days) ] A general effect size measure of half standard deviation will be used to establish the minimally important difference. Descriptive statistics (mean, SD, median, range) will be used to evaluate the distribution of levels and changes for the set of health-related QOL evaluations. Levels and changes will also be assessed graphically. Changes from baseline will be analyzed using linear mixed models based on restricted maximum likelihood estimation with covariance matrix maximizing Akaike information criteria. Models with treatment, assessment time, and treatment by assessment time interaction with and without other predictors will be fit. If there is substantial missingness, will analyze the data according to the methods described in Schluchter and Schluchter, Greene and Beck.
    Time to worsening of FACT-G [ Time Frame: From baseline until a decrease of 9 points, or censored at date of last assessment, assessed up to 6 months post-treatment ] Will be analyzed with Kaplan-Meier methods and Cox regression with the related treatment arm as the only factor. Correlation between time to worsening of symptoms with PFS and OS will be assessed with Kendall's Tau adjusted for censored observations.

    Other Outcome Measures:
    Cumulative dose calculated as the sum of all doses taken across all cycles [ Time Frame: Up to 24 months ] Cumulative dose will be calculated overall and by cycle. Data will be summarized by treatment arm with descriptive statistics and graphically over time. Patients will be classified into dichotomous groups based on a 75% relative dose intensity cutoff (< 75% versus [vs] >= 75% represents poor vs good treatment adherence). The proportion of patients with poor lenalidomide treatment adherence will be compared between arms using the Fisher's exact test. In addition, multi-variable logistic regression analysis will be conducted to identify the baseline factors associated with calculated good treatment adherence.
    Dose intensity calculated as cumulative dose received divided by treatment duration [ Time Frame: Up to 24 months ] Dose intensity will be calculated overall and by cycle. Data will be summarized by treatment arm with descriptive statistics and graphically over time. Patients will be classified into dichotomous groups based on a 75% relative dose intensity cutoff (< 75% vs >= 75% represents poor vs good treatment adherence). The proportion of patients with poor lenalidomide treatment adherence will be compared between arms using the Fisher's exact test. In addition, multi-variable logistic regression analysis will be conducted to identify the baseline factors associated with calculated good treatment adherence.
    Relative dose intensity calculated as the dose intensity divided by planned dose intensity [ Time Frame: Up to 24 months ] Dose intensity will be calculated overall and by cycle. Data will be summarized by treatment arm with descriptive statistics and graphically over time. Patients will be classified into dichotomous groups based on a 75% relative dose intensity cutoff (< 75% vs >= 75% represents poor vs good treatment adherence). The proportion of patients with poor lenalidomide treatment adherence will be compared between arms using the Fisher's exact test. In addition, multi-variable logistic regression analysis will be conducted to identify the baseline factors associated with calculated good treatment adherence.
    Duration of treatment [ Time Frame: From randomization to date off treatment, or censored at the date of last treatment, assessed up to 24 months ] Treatment duration in each arm will be estimated using Kaplan-Meier methods and compared between arms with the log-rank test.
    Time to progression [ Time Frame: From randomization to progression, or censored at date of last disease evaluation, assessed up to 15 years ] Will be estimated using the Kaplan-Meier method.
    Presence, frequency, interference, amount and/or severity of select patient reported outcomes (PRO)-CTCAEs [ Time Frame: Assessed at each treatment cycle, from cycle 1 of treatment to end of treatment, up to 24 cycles of treatment (each cycle is 28 days) ] Descriptive statistics (mean, standard deviation, median, range) will be used to summarize selected PRO-CTCAEs tabulated at each cycle overall and by arm. Will map PRO-CTCAEs with provider reported adverse events (AEs) and evaluate differences in incidence and worst severity. Items correspond to 5 attributes measured [frequency (F), severity (S), interference (I), presence/absence (P) and amount (A)] based on multiple choice questions. Response for each attribute except P which is binary is on a 5-point Likert scale with 5 indicating 'almost constantly' frequency, 'very severe' severity, 'very much' amount or 'very much' interference. An overall PRO-CTCAE score will be calculated at each time point.
    Overall PRO-CTCAE score [ Time Frame: Up to 15 years ] Defined as the sum of item scores on all symptomatic adverse events (AEs). Descriptive statistics will be used to summarize selected PRO-CTCAEs tabulated at each cycle overall and by arm. Will map PRO-CTCAEs with provider reported AEs and evaluate differences in incidence and worst severity. An overall PRO-CTCAE score will be calculated at each time point.
    Adherence Starts with Knowledge (ASK)-12 scores [ Time Frame: At 7, 13, and 19 cycles of treatment (each cycle is 28 days) ] Descriptive statistics will be used to summarize ASK-12 scores tabulated at cycles 7, 13 and 19 overall and by arm. Differences between arms will be evaluated based a t-test (or Wilcoxon rank sum test). Patients will also be classified into high versus low likelihood of medication adherence groups according to tertile distributions (lowest tertile vs second and top). Association between likelihood of medication adherence and calculated treatment adherence dichotomous groups will be evaluated in patients with both ASK-12 and treatment data at cycles 7, 13 and 19 post randomization. In addition, multivariable logistic regression analysis will be conducted to identify the baseline factors associated with low likelihood of medication adherence.
    PRO compliance rate [ Time Frame: Up to 15 years ] Defined as the proportion of patients who submit the given PRO instrument among those eligible at each time point which excludes those missing by design (due to death or disease progression, early treatment discontinuation).
    PRO completion rate [ Time Frame: Up to 15 years ] Defined as the proportion of patients who complete given PRO instrument based on the instrument's scoring system among those eligible at each time point.

    TRIAL NUMBER: ANBL1821

    Title: A PHASE 2 RANDOMIZED STUDY OF IRINOTECAN/TEMOZOLOMIDE/DINUTUXIMAB WITH OR WITHOUT EFLORNITHINE (DFMO) (IND#141913) IN CHILDREN WITH RELAPSED, REFRACTORY OR PROGRESSIVE NEUROBLASTOMA

    Purpose:

    Primary Outcome Measures :
    1. Response rate [ Time Frame: Up to the first 6 cycles of treatment ]
      Responders are defined as patients who achieve a >= minor response (MR) per the International Neuroblastoma Response Criteria (INRC) as their best overall response by the end of 6 cycles. The response rate to treatment will be calculated among all eligible patients, including placement of a 95% confidence interval on the response rate.


    Secondary Outcome Measures :
    1. Progression-free survival (PFS) [ Time Frame: Up to 5 years ]
      Kaplan-Meier method will be used to estimate progression-free survival (PFS). PFS time will be calculated from the time of randomization to the occurrence of relapse, progressive disease, or death. Patients without a PFS event will be censored at the time of last follow-up.

    2. Overall survival (OS) [ Time Frame: Up to 5 years ]
      Kaplan-Meier method will be used to estimate overall survival (OS). OS time will be calculated from the time of randomization to the occurrence of death. Patients still alive will be censored at the time of last follow-up.

    3. Incidence of adverse events >= Grade 3 (Regimen B) [ Time Frame: Up to 5 years ]
      The percentage of patients on Regimen B with at least one Grade 3 or higher toxicity will be calculated, assessed with Common Terminology Criteria for Adverse Events version 5.0.


    Other Outcome Measures:
    1. Immune and cytokine profiles [ Time Frame: Up to 6 cycles ]
      Will be assessed by exploring the relationship between response (responder versus [vs.] non-responder) after 6 cycles on Regimen B with serum cytokine levels (IL1, IL6, tumor necrosis factor [TNF]-alpha, IFN-gamma, etc.), tumor resident immune cells (natural killer [NK] cells, tumor-associated macrophages [TAMS], tumor infiltrating lymphocyte [TILS]), and critical immune cell suppressing proteins (B7H3, PDL-1) using Fisher's exact test for categorical and Wilcoxon rank-sum test for continuous factors.

    2. GD2 levels in tumor cells from bone marrow samples [ Time Frame: Up to 5 years ]
      Will be correlated with response (responder vs. non-responder) after 6 cycles using Fisher?s exact test for categorical and the Wilcoxon rank-sum test for continuous factors.

    3. Patient reported pain and opiate usage [ Time Frame: Up to 5 years ]
      The occurrence of pain on each regimen as reported by patient report and opiate use will be descriptively summarized. Descriptive and summary statistics will be used to describe the scores from the Faces Pain Scale-Revised during the dinutuximab infusion and on day 1 with irinotecan and temozolomide alone for each arm separately. Confidence intervals will be constructed for the mean and frequency estimates. The day 1 patient reported outcome data are expected to be similar between the 2 regimens, while differences during or after completion of treatment may be observed.

    TRIAL NUMBER: A191402CD

    Title: Decision Aids in Improving Knowledge in Patients With Newly Diagnosed Prostate Cancer

    Purpose: This randomized phase III trial studies how well decision aids work in improving knowledge in patients with newly diagnosed prostate cancer. Decision aids may improve patients' knowledge of their condition and options for treatment, and may also help when talking with their doctor.

    TRIAL NUMBER: NRG-GU002

    Title: NRG-GU002: PHASE II-III TRIAL OF ADJUVANT RADIOTHERAPY AND ANDROGEN DEPRIVATION FOLLOWING RADICAL PROSTATECTOMY WITH OR WITHOUT ADJUVANT DOCETAXEL

    Purpose: This randomized phase II/III trial studies docetaxel, antiandrogen therapy, and radiation therapy to see how well it works compared with antiandrogen therapy and radiation therapy alone in treating patients with prostate cancer that has been removed by surgery. Androgen can cause the growth of prostate cells. Antihormone therapy may lessen the amount of androgen made by the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving antiandrogen therapy and radiation therapy with or without docetaxel after surgery may kill any remaining tumor cells.

    TRIAL NUMBER: AREN1721

    Title: A RANDOMIZED PHASE 2 TRIAL OF AXITINIB/NIVOLUMAB COMBINATION THERAPY VS. SINGLE AGENT AXITINIB OR NIVOLUMAB FOR THE TREATMENT OF TFE/TRANSLOCATION RENAL CELL CARCINOMA (tRCC) ACROSS ALL AGE GROUPS

    Purpose:

    Primary Outcome Measures :
    1. Progression free survival [ Time Frame: From initiation of treatment assessed up to 4 years ]

    Other Outcome Measures:
    1. Translocation morphology renal cell carcinoma clinical behavior [ Time Frame: Up to 4 years ]
      Will list and summarize the frequency of site(s) of disease at presentation (including extent of lymph node involvement), site(s) of relapse, surgical practices on protocol therapy, and radiotherapy practices on protocol therapy.

    2. Type of antitumor immune response and stability of T cell activation [ Time Frame: Baseline up to 4 years ]
      Will summarize the levels of analytes and tumor expression before and after treatment and evaluate the changes due to treatment after logarithmic transformation using the paired t-test. Analytes include myeloid derived stem cells: CD45, CD11b, CD33, CD14, CD15, HLA-DR, viability, stain 1; regulatory T cells: viability, CD45, CE4, CD3, CD24, FoxP3; CD8 T cells (CD45, CD8, CD3); CD8 phenotype and activation and exhaustion (CD69, CD38, PD1, CD244, TIM3). Tumor expression of PDL-1, PD1, CD3, CD4 and CD8 will be assessed using TFE renal cell carcinoma samples from the study and scored for intensity (0 - 3).

    TRIAL NUMBER: S1400F

    Title: A PHASE II STUDY OF MEDI4736 (DURVALUMAB) PLUS TREMELIMUMAB AS THERAPY FOR PATIENTS WITH PREVIOUSLY TREATED ANTI-PD-1/PD-L1 RESISTANT STAGE IV SQUAMOUS CELL LUNG CANCER (LUNG-MAP NON-MATCH SUB-STUDY)

    Purpose: Primary Outcome Measures: Investigator-assessed progression-free survival as defined by Response Evaluation Criteria in Solid Tumors 1.1 (Design #1, Phase II) [ Time Frame: From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 18 months since completion of accrual ] A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to investigator-assessed progression-free survival, comparing the two treatment arms.
    Investigator-assessed progression-free survival in patients with advanced stage refractory squamous cell carcinoma of the lung randomized to receive investigational therapy vs standard therapy (Design #2,Phase III,Option for Biomarker-driven sub-studies) [ Time Frame: Up to 3 years ] Estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median investigator-assessed progression-free survival. A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to progression free survival comparing the two treatment arms at the levels specified.
    Less than 33% improvement in median investigator-assessed progression-free survival as defined as Response Evaluation Criteria in Solid Tumors 1.1 (Design #1, Phase III) [ Time Frame: From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 18 months since completion of accrual ] A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to investigator-assessed progression-free survival, comparing the two treatment arms. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.
    Objective response rate (confirmed and unconfirmed, complete and partial) (Design #2, Phase II, Option for Biomarker-driven Sub-studies) [ Time Frame: Up to 3 years ] The investigational therapy arm will be judged to have provided sufficient evidence to proceed to the Phase III component if the objective response rate is at least 25%. Response rates and associated confidence intervals will be calculated.
    Objective response rate (confirmed and unconfirmed, complete and partial) in patients treated with investigational non-match therapy with advanced stage refractory squamous cell carcinoma of the lung (Design #2, Option for Non-Match Sub-Studies) [ Time Frame: Up to 3 years ] Response rates and associated confidence intervals will be calculated.
    Overall survival (Design #1, Phase III) [ Time Frame: From date of sub-study registration (or date of screening registration if patient never enrolls in a sub-study) to date of death due to any cause, assessed up to 3 years ] A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to overall survival, comparing the two treatment arms. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.
    Overall survival in patients with advanced stage refractory squamous cell carcinoma of the lung randomized to receive investigational therapy versus standard therapy (Design #2, Phase III, Option for Biomarker-driven Sub-studies) [ Time Frame: Up to 3 years ] The Brookmeyer-Crowley method will be used to calculate confidence intervals for median overall survival. A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to overall survival comparing the two treatment arms at the levels specified.

    Secondary Outcome Measures: Duration of response among patients who achieve a complete response or partial response by Response Evaluation Criteria in Solid Tumors 1.1 (Design #2, Phase II, Option for Biomarker-driven Sub-studies and Design #2, Option for Non-Match Sub-studies) [ Time Frame: Up to 3 years ] Estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median duration of response.
    Frequency and severity of toxicities associated with investigational therapy versus standard therapy (Design #2, Phase III, Option for Biomarker-driven Sub-studies) [ Time Frame: Up to 3 years ] Analysis of toxicities will be performed using a chi-square or Fisher?s exact test, as appropriate.
    Investigator-assessed progression-free survival, censoring patients with symptomatic deterioration at the time of symptomatic deterioration (Design #1, Phase III) [ Time Frame: From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 3 years ] Descriptive data will be presented.
    Overall survival with investigational therapy (Design #2, Phase II, Option for Biomarker-driven Sub-studies and Design #2, Option for Non-Match Sub-studies) [ Time Frame: Up to 3 years ] A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to overall survival comparing the two treatment arms at the levels specified. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.
    Progression free survival with investigational therapy (Design #2, Phase II, Option for Biomarker-driven Sub-studies and Design #2, Option for Non-Match Sub-studies) [ Time Frame: Up to 3 years ] A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to progression free survival comparing the two treatment arms at the levels specified. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.
    Response rate (confirmed and unconfirmed) in patients with measurable disease as defined by Response Evaluation Criteria in Solid Tumors 1.1 (Design #1, Phase II and III) [ Time Frame: Up to 3 years ] Analysis will be performed using a chi squared or Fisher?s exact test, as appropriate. Response proportions will be compared using a 1-sided Fisher?s exact test at the 0.001 level.
    Response rates (confirmed and unconfirmed, complete and partial) among patients randomized to receive investigational therapy versus standard therapy (Design #2, Phase III, Option for Biomarker-driven Sub-studies) [ Time Frame: Up to 3 years ] Analysis of response rates will be performed using a chi-square or Fisher?s exact test, as appropriate.
    Severity of toxicities associated with investigational therapy versus standard therapy (Design #2, Phase II, Option for Biomarker-driven Sub-studies and Design #2, Option for Non-Match Sub-studies) [ Time Frame: Up to 3 years ] Analysis of toxicities will be performed using a chi-square or Fisher?s exact test, as appropriate.
    Toxicity frequencies, monitored using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Design #1, Phase II and III) [ Time Frame: Up to 3 years ] Analysis will be performed using a chi squared or Fisher?s exact test, as appropriate.

    Other Outcome Measures: Screen success rate, monitored by the percentage of screened patients that register to a therapeutic sub-study [ Time Frame: Up to 3 years ] Descriptive data will be presented.
    Treatment arm randomization acceptance rate, monitored by the percentage of patients that receive at least one dose of the treatment they are randomized to (Design #1) [ Time Frame: Up to 3 years ] Descriptive data will be presented.

    Estimated Enrollment: 10000 Actual Study Start Date: June 16, 2014 Estimated Study Completion Date: April 1, 2022 Estimated Primary Completion Date: April 1, 2022 (Final data collection date for primary outcome measure)

    TRIAL NUMBER: APEC1621 (Master)

    Title: NCI-COG PEDIATRIC MATCH (MOLECULAR ANALYSIS FOR THERAPY CHOICE) MASTER VERSION CONTROL PROTOCOL

    Purpose:

    TRIAL NUMBER: APEC1621J

    Title: NCI-COG PEDIATRIC MATCH (MOLECULAR ANALYSIS FOR THERAPY CHOICE)- PHASE 2 SUBPROTOCOL OF BVD-523FB (ULIXERTINIB) IN PATIENTS WITH TUMORS HARBORING ACTIVATING MAPK PATHWAY MUTATIONS

    Purpose: Primary Outcome Measures : Objective response rate (ORR = complete response [CR] + partial response [PR]) in pediatric patients treated with BVD-523FB (ulixertinib) [ Time Frame: Up to 2 years ] Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed using the Wilson score interval method

    Secondary Outcome Measures : Progression free survival (PFS) in pediatric patients treated with ulixertinib [ Time Frame: From initiation of treatment to disease progression, disease recurrence, or death from any cause assessed up to 2 years ] PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.
    Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events version 5.0 [ Time Frame: Up to 2 years ] Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. A patient will be counted only once for a given toxicity for the worst grade of that toxicity reported for that patient. Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen.
    Preliminary estimates of the pharmacokinetics of ulixertinib in children and adolescents with relapsed or refractory cancer [ Time Frame: Pre-dose and 1, 2, 4, and 6-8 hours after dose on course 1, day 1; and pre-dose on course 1, day 2, and course 1, day 15 ] Will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

    Other Outcome Measures: Other biomarkers as predictors of response to ulixertinib and whether tumors that harbor different mutations or fusions will demonstrate differential response to treatment [ Time Frame: Up to 2 years ] Will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.
    Profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA) [ Time Frame: Up to 2 years ] Will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.

    TRIAL NUMBER: A091605

    Title: A RANDOMIZED PHASE II STUDY OF ANTI-PD1 ANTIBODY [MK-3475 (PEMBROLIZUMAB)] ALONE VERSUS ANTI-PD1 ANTIBODY PLUS STEREOTACTIC BODY RADIATION THERAPY IN ADVANCED MERKEL CELL CARCINOMA

    Purpose: This randomized phase II trial studies how well pembrolizumab with or without stereotactic body radiation therapy works in treating patients with merkel cell cancer that has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy is a specialized radiation therapy that sends x-rays directly to the tumor using smaller doses over several days and may cause less damage to normal tissue. Giving pembrolizumab with stereotactic body radiation therapy may work better in treating patients with merkel cell cancer.

    TRIAL NUMBER: A031501

    Title: PHASE III RANDOMIZED ADJUVANT STUDY OF MK-3475 (PEMBROLIZUMAB) IN MUSCLE INVASIVE AND LOCALLY ADVANCED UROTHELIAL CARCINOMA (AMBASSADOR) VERSUS OBSERVATION

    Purpose: Primary Outcome Measures: Disease-free survival [ Time Frame: From randomization to the first metastatic recurrence (presence of any recurrent disease), or death, whichever occurs first, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.
    Overall survival [ Time Frame: From randomization to the date of death from any cause, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.

    Secondary Outcome Measures: Disease-free survival in PD-L1 positive and negative patients [ Time Frame: From randomization to the first metastatic recurrence (presence of any recurrent disease), or death, whichever occurs first, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.
    Overall survival in PD-L1 positive and negative patients [ Time Frame: From randomization to the date of death from any cause, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.

    Estimated Enrollment: 739 Actual Study Start Date: September 21, 2017 Estimated Study Completion Date: February 28, 2019 Estimated Primary Completion Date: February 28, 2019 (Final data collection date for primary outcome measure)

    • Ochsner Medical Center Jefferson
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    TRIAL NUMBER: ACNS1422

    Title: A Phase 2 Study of Reduced Therapy for Newly Diagnosed Average-Risk WNT-Driven Medulloblastoma Patients

    Purpose: Primary Outcome Measures: PFS [ Time Frame: From the initiation of protocol treatment to the occurrence of any of the following events: disease progression or disease recurrence or death from any cause, assessed up to 10 years ] PFS along with the confidence intervals will be estimated using the Kaplan-Meier method. PFS will also be reported based on central radiology review.

    Secondary Outcome Measures: Change in neurocognitive function (cognitive, social, emotional and behavioral) according to Children Oncology Group Standard Neuropsychological Battery [ Time Frame: Baseline to up to 60 months post-diagnosis ] Neurocognitive function will be measured at 9, 30 and 60 months post diagnosis and will be compared with the neurocognitive outcomes from an age and gender matched ACNS0331 cohort to the WNT patients treated on ACNS1422. Data for all assessments will be available as standardized t-scores. The change over time for each component of the neuropsychological testing will be estimated using the Generalized Estimating Equation (GEE) approach, with the standardized t-scores as the dependent variable and the assessment times as a covariate. Within the ACNS1422 cohort GEE models will also be used to exp
    DNA methylation profiling as real-time classification of WNT-driven medulloblastoma [ Time Frame: Within 32 days of definitive surgery ] Results will be compared to the results of the molecular screening tests. The sensitivity and specificity comparison between DNA methylation arrays and the standard methods (molecular screening tests for WNT using IHC and CTNNB1 sequencing) will be performed using McNemar's test.

    Other Outcome Measures: DNA methylation profiling of medulloblastoma real-time" predictive classification scheme for the SHH, group 3 and group 4 medulloblastoma subgroups according to the Heidelberg classifier [ Time Frame: Within 32 days of definitive surgery ] The proportion of patients classified into each medulloblastoma subgroup in "real time" will be reported.

    Estimated Enrollment: 45 Study Start Date: October 2016 Estimated Primary Completion Date: May 2025 (Final data collection date for primary outcome measure)

    TRIAL NUMBER: ANBL00B1

    Title: NEUROBLASTOMA BIOLOGY STUDIES

    Purpose:

    TRIAL NUMBER: ANBL1232

    Title: Utilizing Response- and Biology-Based Risk Factors to Guide Therapy in Patients with Non-High-Risk Neuroblastoma; A Groupwide Historically-Controlled Phase III Study

    Purpose: PRIMARY OBJECTIVES:
    I. To eliminate therapy as the initial approach for infants < 12 months of age with small International Neuroblastoma Risk Group (INRG) stage L1 neuroblastoma while maintaining an overall survival (OS) of 99%.
    II. To eliminate therapy as the initial approach for non-high-risk patients < 18 months of age with localized neuroblastoma and favorable biology (histologic and genomic features) while maintaining an OS of 99%.
    III. To achieve a 3-year OS of > 81% for infants < 18 months of age with INRG stage Ms neuroblastoma using objective criteria for early initiation of a response-based treatment algorithm.
    IV. To achieve a 3-year event free survival (EFS) of > 70% for non-high-risk infants < 12 months of age with INRG stage M neuroblastoma and unfavorable biology (histologic and/or genomic features) through the addition of isotretinoin therapy.
    SECONDARY OBJECTIVES:
    I. To describe the time to intervention or tumor progression, type of intervention and site of progression for patients with localized neuroblastoma who experience progression after an initial period of observation.
    II. To characterize the pharmacokinetic profile of the chemotherapeutic agents carboplatin and etoposide in patients with stage Ms disease.
    III. To define the genomic profile of tumors from patients with non-high-risk neuroblastoma both at initial biopsy and at the time of subsequent biopsy or surgical resection.
    IV. To describe the histology of tumor specimens obtained at the time of subsequent biopsy or surgical resection.
    V. To determine the salvage rate (OS) of patients with tumor relapse or disease progression.
    VI. To determine the procedural complication rate (initial biopsy, resection [intraoperative and postoperative], subsequent biopsy) and correlate with the degree of surgical resection.
    VII. To determine the rate of reduction in image defined risk factors (IDRF) in L2 tumors following observation or chemotherapy.
    VIII. To describe bone abnormalities on bilateral tibial radiographs obtained before and after isotretinoin therapy.
    IX. To determine the variability of isotretinoin pharmacokinetics and relationship to pharmacogenomic parameters and determine if these levels and/or genetic variations correlate with EFS or systemic toxicity.
    OUTLINE: Patients are assigned to 1 of 4 treatment groups.
    GROUP A: Patients undergo clinical observation for 96 weeks.
    GROUP B: Patients undergo clinical observation for 3 years in the absence of disease progression. Upon disease progression, patients undergo surgery or receive first-line chemotherapy comprising carboplatin intravenously (IV) over 1 hour on day 1 (courses 1, 2, 4, 6, and 7), etoposide IV over 1 hour on days 1-3 (courses 1, 3, 4, 5, and 7), cyclophosphamide IV over 1 hour on day 1 (courses 2, 3, 5, 6, and 8), and doxorubicin hydrochloride IV over 15 minutes on day 1 (courses 2, 4, 6 and 8). Treatment with chemotherapy repeats every 21 days for 2-8 courses in the absence of disease progression or unacceptable toxicity. Once a partial response (PR) or better is achieved, patients undergo clinical observation for 3 years.
    GROUP C: Patients at high risk for deterioration and a poor outcome immediately receive first-line chemotherapy as in Group B. All other patients undergo clinical observation for 3 years in the absence of disease progression. Upon disease progression, patients receive first-line chemotherapy as in Group B. Once a PR or better is achieved, patients undergo clinical observation for 3 years.
    GROUP D: Patients receive first-line chemotherapy as in Group B. Patients who achieve a complete response (CR) or very good partial response (VGPR) following first-line chemotherapy receive isotretinoin orally (PO) twice daily (BID) on days 1-14. Treatment with isotretinoin repeats every 28 days for 6 courses. Patients then undergo clinical observation for 3 years. Patients who achieve a PR or stable disease (SD) following first-line chemotherapy receive salvage chemotherapy comprising cyclophosphamide IV over 30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment with salvage chemotherapy repeats every 21 days for 2-6 courses. Patients then receive isotretinoin PO BID on days 1-14. Treatment with isotretinoin repeats every 28 days for 6 courses. Patients then undergo clinical observation for 3 years.
    After completion of study treatment, patients are followed up annually for 5 years.

    TRIAL NUMBER: A011202

    Title: A Randomized Phase III Trial Evaluating the Role of Axillary Lymph Node Dissection in Breast Cancer Patients (CT1-3 N1) Who Have Positive Sentinel Lymph Node Disease After Neoadjuvant Chemotherapy

    Purpose: Study Outline: All patients will undergo surgery to identify sentinel lymph node(s). If a lymph node (sentinel or non-sentinel) is determined to be positive on intra-operative pathology the patient will be registered/randomized intra-operatively. Patients who do not have a sentinel lymph node identified will not be registered/randomized to the study. Patients whose sentinel lymph node status is cannot be/is not determined intra- operatively, and have not undergone ALND, but had at least one lymph node (sentinel or non-sentinel) found to be positive on final pathology review will be registered/randomized post-operatively. Patients whose sentinel lymph node status is found to be negative intra-operatively and have not undergone ALND, but had at least one lymph node (sentinel or non-sentinel) found to be positive on final pathology review will be registered/randomized post-operatively. ALND is not to be performed prior to registration/randomization. Patients who are determined to have negative lymph nodes on final pathology will not be registered/randomized, but can be offered participation in another cooperative group trial. The primary and secondary objectives of the study are described below. Please see the "Arms" section for a detailed description of the treatment regimens. Primary Objective: To evaluate whether radiation to the undissected axilla and regional lymph nodes is not inferior to axillary lymph node dissection with radiation to the regional lymph nodes but not to the dissected axilla in terms of invasive breast cancer recurrence-free interval in patients with positive SLN(s) after completion of neoadjuvant chemotherapy Secondary Objectives: To evaluate whether radiation to the undissected axilla and regional lymph nodes is not inferior to axillary lymph node dissection with radiation to the regional lymph nodes but not to the dissected axilla in terms of the incidence of invasive loco-regional recurrences in patients with a positive SLN(s) after completion of neoadjuvant chemotherapy To obtain an estimate of the distribution of residual disease burden scores for each treatment arm To estimate the distribution of overall survival for each treatment arm Patients may receive adjuvant and ancillary therapy as appropriate per the protocol. Adjuvant Therapy: Adjuvant endocrine therapy: Patients with hormone receptor (ER and/or PR) positive disease should receive a minimum of 5 years of standard endocrine therapy (experimental agents/regimens are not permitted). Endocrine therapy should begin following completion of neoadjuvant chemotherapy and surgery, either before, during or after radiation therapy at the discretion of the oncologist. Selection of the agents is at the treating physician's discretion. Patients with HER 2 positive disease should complete a total of one year of trastuzumab therapy (over the neoadjuvant and adjuvant period). Chemotherapy, biologic therapy or vaccine therapy in the adjuvant setting is not allowed. Patients who wish to receive any of these therapies after surgery must go off study at the time of their initiation. Ancillary Therapy: Patients should receive full supportive care, including transfusions of blood and blood products, erythropoetin (unless otherwise specified in the protocol), antibiotics, antiemetics, etc. when appropriate. Patients are followed up for 5 years after completion of radiation therapy.

    TRIAL NUMBER: A011401

    Title: A011401: Study Title for Study Participants: Breast Cancer WEight Loss Study (BWEL Study) Official Study Title for Internet Search on http://www.ClinicalTrials.gov: Randomized Phase III Trial Evaluating the Role of Weight Loss in Adjuvant Treatment of Overweight and Obese Women with Early Breast Cancer

    Purpose: This study is being done to see if losing weight may help prevent breast cancer from coming back (recurring). Previous studies have found that women who are overweight or obese when their breast cancer is found (diagnosed) have a greater risk of their breast cancer recurring, as compared to women who were thinner when their cancer was diagnosed. At this time we do not know whether or not losing weight will reduce the risk of breast cancer returning. This study seeks to determine whether or not the higher risk for breast cancer recurrence in women who are overweight or obese when they are diagnosed with breast cancer could be reduced or eliminated if weight is lost. It is important to note that we do not know how much weight would need to be lost to lower the risk of breast cancer recurrence, or whether this strategy would work for all women. This study will help to show us whether weight loss programs should be a part of breast cancer treatment.

    TRIAL NUMBER: A221505

    Title: PHASE III RANDOMIZED TRIAL OF HYPOFRACTIONATED POST MASTECTOMY RADIATION WITH BREAST RECONSTRUCTION

    Purpose: 2.1 Primary Objective To evaluate whether the reconstruction complication rate at 24 months post radiation is non-inferior with hypofractionation. Complications will include those listed in Section 10.1. 2.2 Secondary Objectives 2.2.1 To evaluate the incidence of acute and late radiation complications based on CTCAE 4.0 toxicity. 2.2.2 To evaluate the local and local regional recurrence rate. 2.2.3 To compare reconstruction complication rates based on reconstruction method (autologous +/- implant vs implant only) and timing of reconstruction received (immediate vs. intent for delayed).

    TRIAL NUMBER: EA1131

    Title: A Randomized Phase III Post-Operative Trial of Platinum Based Chemotherapy Vs. Observation in Patients with Residual Triple-Negative Basal-Like Breast Cancer following Neoadjuvant Chemotherapy

    Purpose: The purpose of this study is to compare the IDFS in TNBC patients with residual basal-like disease after neoadjuvant chemotherapy who are randomized to post-preoperative platinum based chemotherapy with those who are randomized to observation. At present, upon completion of neoadjuvant therapy, the standard of care for patients with TNBC (who have no clinical evidence of metastatic disease after surgical excision of the cancer regardless of burden of residual disease) is observation, since there is no additional therapies available with proven impact. This study could provide a possible alternative treatment, which makes it appropriate for the population.

    TRIAL NUMBER: NRG-BR003

    Title: A Randomized Phase III Trial of Adjuvant Therapy Comparing Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel With or Without Carboplatin for Node-Positive or High-Risk Node-Negative Triple-Negative Invasive Breast Cancer

    Purpose: This randomized phase III trial studies how well doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel with or without carboplatin work in treating patients with triple-negative breast cancer. Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether doxorubicin hydrochloride and cyclophosphamide is more effective when followed by paclitaxel alone or paclitaxel and carboplatin in treating triple-negative breast cancer.

    TRIAL NUMBER: NSABP B-51

    Title: A Randomized Phase III Clinical Trial Evaluating Post-Mastectomy Chestwall and Regional Nodal XRT and Post-Lumpectomy Regional Nodal XRT in Patients With Positive Axillary Nodes Before Neoadjuvant Chemotherapy Who Convert to Pathologically Negative Axillary Nodes After Neoadjuvant Chemotherapy

    Purpose: This randomized phase III trial studies standard or comprehensive radiation therapy in treating patients with early-stage breast cancer who have undergone surgery. Radiation therapy uses high-energy x rays to kill tumor cells. It is not yet known whether comprehensive radiation therapy is more effective than standard radiation therapy in treating patients with breast cancer

    TRIAL NUMBER: S1418

    Title: A Randomized, Phase III Trial to Evaluate the Efficacy and Safety of MK-3475 (Pembrolizumab) as Adjuvant Therapy for Triple Receptor-Negative Breast Cancer With ? 1 cm Residual Invasive Cancer or Positive Lymph Nodes (ypN+) After Neoadjuvant Chemotherapy

    Purpose: This randomized phase III trial studies how well pembrolizumab works in treating triple-negative breast cancer. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

    TRIAL NUMBER: S1501

    Title: PROSPECTIVE EVALUATION OF CARVEDILOL IN PREVENTION OF CARDIAC TOXICITY IN PATIENTS WITH METASTATIC HER-2+ BREAST CANCER, PHASE III

    Purpose: Primary Objective To assess whether prophylactic beta blocker therapy with carvedilol compared with no intervention reduces the risk of subsequent cardiac dysfunction in patients with metastatic breast cancer receiving trastuzumab?based HER-2 targeted therapy. Secondary Objectives a. To assess whether prophylactic beta blocker therapy with carvedilol compared with no intervention reduces the risk of predefined subsequent cardiac events in patients with metastatic breast cancer receiving trastuzumab?based HER-2 targeted therapy. b. To evaluate if prophylactic carvedilol compared with no intervention results in a longer time to first interruption of trastuzumab?based HER-2 targeted therapy due to either cardiac dysfunction or events. c. To assess whether prophylactic beta blocker therapy with carvedilol compared with no intervention reduces the risk of subsequent cardiac dysfunction OR events in this population. d. To establish and prospectively collect a predefined panel of baseline core cardiovascular measures and develop a predictive model of cardiac dysfunction (see Section 11.2). e. To evaluate the rate of cardiac dysfunction in an observational arm consisting of individuals otherwise eligible for the study except for use of beta blockers, angiotensin receptor blocker (ARB), or angiotensin converting enzyme (ACE) inhibitors for other medical reasons.

    TRIAL NUMBER: ALTE11C2

    Title: HEALTH EFFECTS AFTER ANTHRACYCLINE AND RADIATION THERAPY (HEART): DEXRAZOXANE AND PREVENTION OF ANTHRACYCLINE-RELATED CARDIOMYOPATHY

    Purpose: Given the critical role anthracyclines have in many effective cancer treatments and the risk for subsequent cardiotoxicity associated with this class of agents, development of an effective cardioprotective strategy is of great importance. Although adult studies have shown that dexrazoxane (DRZ) is effective in minimizing cardiomyopathy/heart failure (CHF) after anthracycline therapy, short and long-term data in children are much more limited. Furthermore, concerns regarding DRZ's interaction with cancer therapies and possible association with an increased risk of second cancers have limited its use among children despite possible protection against premature CHF. To address these gaps in knowledge, using a cross-sectional study design, we propose to ascertain echocardiographic and serum biomarkers of cardiac injury in a cohort of long-term pediatric T-cell leukemia and Hodgkin lymphoma survivors enrolled on 3 front-line Children's Oncology Group (COG) clinical trials (POG 9404, 9425, 9426) between 1996-2001 that featured upfront DRZ randomization and a range of anthracycline exposures commonly used in contemporary therapy (100-360 mg/m2 doxorubicin). Our primary aim will be to determine whether patients randomized to the experimental DRZ arms have decreased markers of myocardial injury compared with patients treated without DRZ. Specifically, this will include a one-time measurement of an echocardiographic index of pathologic left ventricular (LV) remodeling (wall thickness-dimension ratio), complemented by serum biomarkers and a physical examination for signs and symptoms of CHF. We will also evaluate whether DRZ's cardioprotective effect is modified by anthracycline dose, chest radiation, and selected demographic factors (age at cancer diagnosis, current age, sex). In secondary analysis, we will also update the overall- and event-free survival rates between patients on the DRZ and non-DRZ arms. Finally, we will determine whether projected quality-adjusted life years differed by randomization status, accounting for premature cardiac disease, primary disease relapse, and second cancers.

    TRIAL NUMBER: DCP-001

    Title: DCP-001, Use of a Clinical Trial Screening Tool to Address Cancer Health Disparities in the NCI Community Oncology Research Program (NCORP)

    Purpose: The protocol is not a scientific study; rather, a method to implement the screening tool and allow the collection and analyses of expanded data with informed consent. Investigators also enroll patients into NCI-treatment trials. The tool, based on a screening log successfully used within the NCI Community Cancer Centers Program (NCCCP), has been streamlined and integrated into the sites’ workflow by using OPEN. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. Also missing from the existing data is the context of care, within the communities themselves where most cancer and at risk of cancer patients receive care which is the focus of NCORP. The profile of patients accrued to NCI-sponsored clinical trials lacks both racial/ethnic and socioeconomic diversity. Accrued patients tend to be insured, highly educated and of higher socioeconomic means. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. NCORP's clinical trials portfolio includes cancer control, prevention, screening, symptom science, and cancer care delivery research.

    TRIAL NUMBER: WF-10217

    Title: Work Ability in Young Adult Survivors (WAYS)

    Purpose: Brief Summary: To document levels of labor force participation, occupation, educational attainment, and financial toxicity following cancer treatment in YA cancer survivors aged 25-34 years.
    Detailed Description: This observational, cross-sectional study will recruit 200 YA survivors through the Wake Forest National Cancer Institute Community Oncology Research Program (NCORP) Research Base (WF NCORP RB). Data will be collected using a web-based interface and will capture physical, psychosocial and cognitive late effects; work ability; work-related outcomes, including labor force participation, occupation, work place characteristics, and educational attainment; survivor characteristics; and cancer diagnosis/treatment information (from clinical records). We will evaluate the relationships among these measures using the theoretical framework to guide statistical analysis.

    TRIAL NUMBER: A021502

    Title: Randomized Trial of Standard Chemotherapy Alone or Combined With Atezolizumab as Adjuvant Therapy for Patients With Stage III Colon Cancer and Deficient DNA Mismatch Repair

    Purpose: This randomized phase III trial studies combination chemotherapy and atezolizumab to see how well it works compared with combination chemotherapy alone in treating patients with stage III colon cancer and deficient deoxyribonucleic acid (DNA) mismatch repair. Drugs used in combination chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as atezolizumab, may interfere with the ability of tumor cells to grow and spread. Giving combination chemotherapy with atezolizumab may work better than combination chemotherapy alone in treating patients with colon cancer.

    TRIAL NUMBER: EA2174

    Title: A PHASE II/III STUDY OF PERI-OPERATIVE NIVOLUMAB AND IPILIMUMAB IN PATIENTS WITH LOCOREGIONAL ESOPHAGEAL AND GASTROESOPHAGEAL JUNCTION ADENOCARCINOMA

    Purpose: Primary Outcome Measures : Pathologic complete response (Step I) [ Time Frame: Up to 5 weeks ] The study with compare the pathologic complete response of Arm A and Arm B using a one-sided 0.10 level chi-squared test for proportions.
    Disease-free survival (DFS) (Step 2) [ Time Frame: From the adjuvant treatment randomization assessed for up to 7 years ] DFS measured from the adjuvant treatment randomization will be the endpoint of the adjuvant portion of the study and to achieve the desired power it is expected that patients will be followed for an additional year post completion of accrual to the adjuvant portion. The DFS comparison will be between patients randomized to Arm C (nivolumab) versus Arm D (nivolumab plus ipilimumab) using a one-sided 0.10 level stratified log rank test.

    Secondary Outcome Measures : Incidence of adverse events [ Time Frame: Up to 7 years ] Graded according to Common Terminology Criteria for Adverse Events version 5.0. Toxicity will be evaluated among all treated patients regardless of eligibility and interim analyses of toxicity are performed twice yearly. The study will have sufficient precision to provide 95% confidence intervals on toxicity
    Overall survival [ Time Frame: From the time of first randomization up to 7 years ] Analyses will be descriptive in nature and will not follow any formal interim monitoring.
    DFS [ Time Frame: From the time of first randomization up to 7 years ] The DFS comparison will be between patients randomized to Arm C (nivolumab) versus Arm D (nivolumab plus ipilimumab) using a one-sided 0.10 level stratified log rank test.

    Other Outcome Measures: Percent change in mean volumetric apparent diffusion coefficient (ADC) [ Time Frame: Baseline to mid-treatment ] The study will assess the area under the receiver operating characteristic curve of the changes of apparent diffusion coefficient (ADC) value.

    TRIAL NUMBER: S0820

    Title: A DOUBLE BLIND PLACEBO-CONTROLLED TRIAL OF EFLORNITHINE AND SULINDAC TO PREVENT RECURRENCE OF HIGH RISK ADENOMAS AND SECOND PRIMARY COLORECTAL CANCERS IN PATIENTS WITH STAGE 0-III COLON CANCER, PHASE III

    Purpose: The purpose of this study is to assess whether eflornithine 500 mg or sulindac 150 mg are effective in reducing the 3-year event rate of high risk adenoma or second primary colorectal cancer in Stage 0, I II and III colon cancer patients. The primary hypothesis will test the main effect of each agent, as well as the comparison of placebo alone to the combination of sulindac and eflornithine.

    TRIAL NUMBER: NRG-GY006

    Title: A Randomized Phase II Trial of Radiation Therapy and Cisplatin Alone or in Combination with Intravenous Triapine in Women with Newly Diagnosed Bulky Stage IB2, Stage II, IIIB, or IVA Cancer of the Uterine Cervix or Stage II-IVA Vaginal Cancer

    Purpose: This randomized phase II trial studies radiation therapy and cisplatin with triapine to see how well they work compared to the standard radiation therapy and cisplatin alone in treating patients with newly diagnosed stage IB2, II, or IIIB-IVA cervical cancer or stage II-IVA vaginal cancer. Radiation therapy uses high energy protons to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether radiation therapy and cisplatin are more effective with triapine in treating cervical or vaginal cancer.

    TRIAL NUMBER: A041701

    Title: A Randomized Phase II/III Study of Conventional Chemotherapy +/- Uproleselan (GMI-1271) in Older Adults With Acute Myeloid Leukemia Receiving Intensive Induction Chemotherapy

    Purpose: This phase II/III trial studies how well daunorubicin and cytarabine with or without uproleselan works in treating older adult patients with acute myeloid leukemia receiving intensive induction chemotherapy. Drugs used in chemotherapy, such as daunorubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Uproleselan may prevent cancer from returning or getting worse. Giving daunorubicin and cytarabine with uproleselan may work better in treating patients with acute myeloid leukemia compared to daunorubicin and cytarabine alone.

    TRIAL NUMBER: R1008

    Title: A RANDOMIZED PHASE II STUDY OF ADJUVANT CONCURRENT RADIATION AND CHEMOTHERAPY VERSUS RADIATION ALONE IN RESECTED HIGH-RISK MALIGNANT SALIVARY GLAND TUMORS

    Purpose: OBJECTIVES:
    Primary ?Determine the feasibility of conducting a cooperative group prospective clinical trial in patients with resected malignant salivary gland tumors. ?Acquire preliminary efficacy data comparing postoperative radiotherapy alone to concurrent chemotherapy and radiation using weekly cisplatin.
    Secondary ?Compare the acute toxicities of these 2 adjuvant treatments. ?Compare long-term efficacy results at 5 years and late treatment-related adverse events in patients receiving postoperative radiation to those receiving concurrent chemoradiation. ?Investigate quality of life and patient-reported outcomes in patients enrolled in the study. ?Identify the histopathology and tumor marker expression from patients enrolled on this trial and assemble a tissue bank for future correlative studies. ?Establish a Radiation Therapy Oncology Group (RTOG) baseline database for salivary gland malignancies to serve as a resource for future exploration of innovative and/or targeted approaches for this disease.
    OUTLINE: This is a multicenter study. Patients are stratified according to histology (high-grade mucoepidermoid carcinoma vs salivary duct carcinoma vs high-grade adenocarcinoma) and nodal status (N0 vs N1-3). Patients are randomized to 1 of 2 treatment arms. ?Arm I: Patients undergo 3-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) 5 days a week for 6-6.5 weeks. Patients also receive cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, 36, and 43 during radiotherapy. ?Arm II: Patients undergo 3D-CRT or IMRT as in arm I. Tissue and blood samples may be collected for translational research studies. Patients may complete quality-of-life assessments periodically.
    After completion of study treatment, patients are followed up at 3, 6, 9, 12, and 24 months, every 6 months for 2 years, and then annually thereafter.

    TRIAL NUMBER: RTOG-1008

    Title: A RANDOMIZED PHASE II/PHASE III STUDY OF ADJUVANT CONCURRENT RADIATION AND CHEMOTHERAPY VERSUS RADIATION ALONE IN RESECTED HIGH-RISK MALIGNANT SALIVARY GLAND TUMORS

    Purpose:

    Primary Outcome Measures :
    1. Progression-free survival (PFS), defined by the events of local-regional progression or recurrence, distant metastasis, or death from any cause, primarily at 2 years [ Time Frame: From randomization to 2 years. ]

    Secondary Outcome Measures :
    1. Overall survival (OS) rate at 2 years [ Time Frame: From randomization to 2 years. ]
    2. PFS rate at 5 years [ Time Frame: From randomization to 5 years. ]
    3. OS rate at 5 years [ Time Frame: From randomization to 5 years. ]
    4. Treatment-related toxicity, defined as any grade 3-4 adverse events (CTCAE v. 4) deemed to be definitely, probably, or possibly related to protocol treatment [ Time Frame: From start of treatment to last follow-up. ]
    5. Treatment-related mortality, defined as any death during or within 30 days of discontinuation of protocol treatment [ Time Frame: From start of treatment to 30 days after the end of treatment. ]
    6. Chemotherapy delivery as measured by percentage of protocol prescription given [ Time Frame: From start of treatment to end of treatment. ]
    7. Radiation delivery as measured by elapsed treatment days [ Time Frame: From start of treatment to end of treatment. ]
    8. Determine whether quality of life, fatigue and xerostomia differ as a function of treatment assignment at 3, 12, and 24 months after completing radiotherapy. [ Time Frame: From randomization to 2 years. ]

    TRIAL NUMBER: APEC14B1

    Title: Project: Every Child for Younger Patients With Cancer

    Purpose: This research trial studies the Project: Every Child for younger patients with cancer. Gathering health information over time from younger patients with cancer may help doctors find better methods of treatment and on-going care.

    TRIAL NUMBER: ARST1431

    Title: COG ARST1431, A Randomized Phase 3 Study of Vincristine, Dactinomycin, Cyclophosphamide (VAC) Alternating with Vincristine and Irinotecan (VI) Versus VAC/VI Plus Temsirolimus (TORI, Torisel, NSC# 683864, IND# 122782) in Patients with Intermediate Risk (IR) Rhabdomyosarcoma (RMS)

    Purpose: ARST1431, states that Unfortunately about 25% of patients with intermediate-risk (IR) embryonal rhabdomyosarcoma (ERMS) and 50% of those with IR alveolar rhabdomyosarcoma (ARMS) will experience disease recurrence with a resulting long-term event-free survival (EFS) of 65%. The mTOR pathway is important in RMS biology, and temsirolimus (TORI), an mTOR inhibitor, has demonstrated clinical activity in patients with relapsed RMS. In an attempt to improve long-term survival for patients with IR RMS, ARST1431 will compare the EFS of patients with newly diagnosed IR RMS randomly assigned to standard vincristine, dactinomycin, and cyclophosphamide (VAC) alternating with vincristine and irinotecan (VI) versus VAC/VI plus TORI. Radiotherapy will start at Week 13 of therapy for all patients. Correlative biology studies will be performed including a determination of the FOXO1 gene fusion status in the tumor and impact on patient outcome. Children’s Hospital/LSUHSC-NO sees several diagnosed patients with Intermediate Risk (IR) Rhabdomyosarcoma (RMS), We estimate seeing up to 5-10 patients per year.

    TRIAL NUMBER: AALL1331

    Title: Risk-Stratified Randomized Phase III Testing of Blinatumomab (IND #117467, NSC #765986) in First Relapse of Childhood B-Lymphoblastic Leukemia (B-ALL): A Groupwide Phase III Study

    Purpose: PRIMARY OBJECTIVES:
    I. To compare disease free survival (DFS) of high-risk (HR) and intermediate-risk (IR) relapse B-cell acute lymphoblastic leukemia (B-ALL) patients who are randomized following induction block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR randomization).
    II. To compare the DFS of low risk (LR) relapse B-ALL patients who are randomized following block 2 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR randomization).
    SECONDARY OBJECTIVES:
    I. To compare overall survival (OS) of HR and IR relapse B-ALL patients who are randomized following induction block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR randomization).
    II. To compare OS of LR relapse B-ALL patients who are randomized following block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR randomization).
    TERTIARY OBJECTIVES:
    I. To compare the rates of minimal residual disease (MRD) >= 0.01% at the end of block 2 and block 3 for HR and IR relapse B-ALL patients in HR/IR randomization.
    II. To estimate, for treatment failure (TF) patients not previously receiving blinatumomab, the hematologic complete remission rate (CR), rate of MRD < 0.01%, and proportion able to proceed to hematopoietic stem cell transplant (HSCT) in CR after treatment with blinatumomab.
    III. To assess the feasibility and safety of rapid taper of immune suppression for the subset of HSCT patients with MRD >= 0.01% pre- and/or post-HSCT with no acute graft versus host disease (aGVHD).
    OUTLINE:
    All patients receive Block 1 over 4 weeks.
    BLOCK 1: Patients receive dexamethasone orally (PO) twice daily (BID) or intravenously (IV) on days 1-5 and 15-19; vincristine sulfate IV over 1 minute on days 1, 8, 15, and 22; pegaspargase IV over 1-2 hours on days 3 and 17; and mitoxantrone hydrochloride IV over 15-30 minutes on days 1-2. Patients with central nervous system (CNS) 1 or CNS2 also receive methotrexate intrathecally (IT) on days 1 and 8. Patients with CNS3 or isolated CNS relapse also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 1, 8, 15, and 22. High risk and intermediate risk patients are then assigned to randomization R1. Low risk patients are assigned to randomization R2.
    RANDOMIZATION R1 (HR and IR patients): Patients are randomized to 1 of 2 treatment arms.
    ARM A: Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, and then undergo allogeneic HSCT.
    ARM B: Patients receive Blinatumomab Block 1 over 5 weeks, Blinatumomab Block 2 over 5 weeks, and then undergo allogeneic HSCT.
    RANDOMIZATION R2 (LR patients): Patients are then randomized to 1 of 2 treatment arms.
    ARM C: Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, Continuation 1 over 8 weeks, Continuation 2 over 8 weeks, and then Maintenance.
    ARM D: Patients receive Block 2 over 4 weeks, Blinatumomab Block 2 over 5 weeks, Continuation 1 over 8 weeks, Blinatumomab Block 3 over 5 weeks, Continuation 2 over 8 weeks, Blinatumomab Block 3 over 5 weeks, and then Maintenance.
    BLOCK 2: Patients receive dexamethasone PO BID or IV on days 1-5; vincristine sulfate IV over 1 minute on day 1; methotrexate IV over 36 hours on day 8; leucovorin calcium IV or PO on days 9-10; pegaspargase IV over 1-2 hours on day 9; cyclophosphamide IV over 15-30 minutes on days 15-19; and etoposide IV over 1-2 hours on days 15-19. Patients with CNS1 or CNS2 also receive methotrexate IT on day 8. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 8 and 22.
    BLOCK 3: Patients receive dexamethasone PO BID or IV on days 1-5; vincristine sulfate IV over 1 minute on day 1; cytarabine IV over 3 hours every 12 hours on days 1, 2, 8, and 9; asparaginase intramuscularly (IM) on days 2, 4, 9, 11, and 23; methotrexate IT on day 1 and IV over 36 hours on day 22; leucovorin calcium PO or IV on days 23-24. Patients with CNS1 or CNS2 also receive methotrexate IT on day 22. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 1 and 22.
    BLINATUMOMAB BLOCK 1: Patients blinatumomab IV continuously on days 1-28 and dexamethasone PO or IV on day 1. Patients with CNS1 or CNS2 also receive methotrexate IT on days 15 and 29. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 15 and 29.
    BLINATUMOMAB BLOCK 2: Patients blinatumomab IV continuously on days 1-28 and dexamethasone PO or IV on day 1. Patients with CNS1 or CNS2 also receive methotrexate IT on days 8 and 29. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 8 and 29.
    BLINATUMOMAB BLOCK 3: Patients blinatumomab IV continuously on days 1-28 and dexamethasone PO or IV on day 1.
    CONTINUATION 1 & 2: Patients receive dexamethasone PO BID or IV on days 1-5; vincristine sulfate IV over 1 minute on day 1; mercaptopurine tablet PO on days 1-42; methotrexate PO on days 8, 15, 29, and 36; leucovorin calcium PO or IV on days 23-24; cyclophosphamide IV over 15-30 minutes on days 42 and 49; etoposide IV over 1-2 hours on days 42 and 49; thioguanine PO once daily on days 42-48; and cytarabine IV or subcutaneously (SC) on days 43-46 and 50-53. Patients with CNS1 or CNS2 also receive methotrexate IT on days 1 and 43. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 1 and 43; methotrexate PO every 6 hours on day 22; and methotrexate IV over 36 hours on day 22.
    MAINTENANCE: Patients receive dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61; vincristine sulfate IV over 1 minute on days 1, 29, and 57; mercaptopurine tablet PO on days 1-84; and methotrexate PO on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Patients with CNS1 or CNS2 also receive methotrexate IT on day 1. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 1. Courses repeat every 12 weeks for up to 2 years since the beginning of treatment in the absence of disease progression or unacceptable toxicity.
    After completion of study treatment, patients are followed up annually for 10 years.

    TRIAL NUMBER: A031704

    Title: PD-Inhibitor (Nivolumab) and Ipilimumab Followed by Nivolumab Vs. VEGF TKI Cabozantinib with Nivolumab: A Phase III Trial in Metastatic Untreated REnal Cell CancEr [PDIGREE]

    Purpose: This phase III trial studies how well nivolumab and ipilimumab, followed by nivolumab versus cabozantinib and nivolumab, work in treating patients with renal cell cancer that is untreated and has spread to other parts of the body. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cabozantinib, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known how well cabozantinib and nivolumab work in treating patients with untreated renal cell cancer that has spread to other parts of the body.

    TRIAL NUMBER: AREN03B2

    Title: RENAL TUMORS CLASSIFICATION, BIOLOGY, AND BANKING STUDY

    Purpose: PRIMARY OBJECTIVES:
    I. Classify patients with renal tumors by histological categorization, surgico- pathological stage, presence of metastases, age at diagnosis, tumor weight, and loss of heterozygosity for chromosomes 1p and 16q, to define eligibility for a series of therapeutic studies.
    II. Maintain a biological samples bank to make specimens available to scientists to evaluate additional potential biological prognostic variables and for the conduct of other research by scientists.
    SECONDARY OBJECTIVES:
    I. Monitor outcome for those patients who are not eligible for a subsequent therapeutic study.
    II. Describe whether the pulmonary tumor burden correlates with outcome in patients with stage IV disease.
    III. Describe the sensitivity and specificity of abdominal computed tomography (CT) scan by comparing it with surgical and pathologic findings for identification of local tumor spread beyond the renal capsule to adjacent muscle and organs, lymph node involvement at the renal hilum and in the retroperitoneum, preoperative tumor rupture, and metastases to the liver.
    IV. Compare the sensitivity and specificity of pre-operative abdominal CT scan and MRI for the identification and differentiation of nephrogenic rests and Wilms' tumor in children with multiple renal lesions.
    V. Correlate the method of conception (natural vs assisted reproductive technology) with the development of Wilms' tumor.
    OUTLINE: This is a multicenter study.
    Tumor tissue, blood, and urine samples are collected for research studies, including immunohistochemistry. CT scans and magnetic resonance imaging (MRIs) are also performed. Loss of heterozygosity analyses (chromosome 1p and 16q) are performed by extraction of DNA. DNA polymorphisms are assayed by polymerase chain reaction using standard methodology. Leftover specimens are archived for future studies.
    Patients are followed periodically for 5 years.

    TRIAL NUMBER: A041501

    Title: A PHASE III TRIAL TO EVALUATE THE EFFICACY OF THE ADDITION OF INOTUZUMAB OZOGAMICIN (A CONJUGATED ANTI-CD22 MONOCLONAL ANTIBODY) TO FRONTLINE THERAPY IN YOUNG ADULTS (AGES 18-39 YEARS) WITH NEWLY DIAGNOSED PRECURSOR B-CELL ALL

    Purpose: Primary Outcome Measures : EFS [ Time Frame: Time from induction response to the time of progressive-disease, secondary malignancy, or death, assessed up to 3 years ] Will be compared using log-rank tests. EFS curves will be constructed using the Kaplan-Meier product limit method, and additional analyses will be done using the Cox proportional hazards model. The corresponding hazard ratio, 2- and 3-year EFS estimates will be assessed, and EFS medians along with their 95% confidence intervals for the two treatment arms.

    Secondary Outcome Measures : DFS [ Time Frame: Time from achievement of CR to the time of relapse and/or death, assessed up to 10 years ] OS [ Time Frame: Time from randomization to the time of death due to any cause, assessed up to 10 years ] Will be evaluated using Kaplan-Meier as well as Cox regression models.
    Proportion of patients who achieve CR or any response to induction therapy [ Time Frame: Up to 10 years ] Will be summarized as the proportion of patients who achieve any type of response to induction therapy divided by the number of all evaluable patients registered to this trial and who received at least one dose of induction therapy. Corresponding 95% binomial confidence intervals will also be calculated.
    Overall induction response rates [ Time Frame: Up to 10 years ] Will be summarized as the proportion of patients who achieve any type of response to induction therapy divided by the number of all evaluable patients registered to this trial and who received at least one dose of induction therapy. Corresponding 95% binomial confidence intervals will also be calculated.
    Incidence of adverse events as assessed by Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 10 years ] The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. In addition, all adverse event data that is graded as 3, 4, or 5 will be reviewed and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The incidence of severe (grade 3+) adverse events or toxicities will be described for each treatment arm, but will also be compared between the arms. Fisher's exact tests will be used to quantitatively compare the incidence of severe as well as specific toxicities of interest between the treatment arms and we will graphically assess differences in maximum grades observed for toxicities between the arms. Tolerability of the treatment arms will be assessed through assessing the number of patients who required dose modifications and/or dose delays.
    Proportion of patients who go off treatment due to adverse reactions [ Time Frame: Up to 10 years ] Will be assessed within each of the treatment arms and differences explores in these measures between the arms.
    Proportion of patients who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial [ Time Frame: Up to 10 years ] Will be assessed within each of the treatment arms and differences explores in these measures between the arms.

    TRIAL NUMBER: A041702

    Title: A RANDOMIZED PHASE III STUDY OF IBRUTINIB PLUS OBINUTUZUMAB VERSUS IBRUTINIB PLUS VENETOCLAX AND OBINUTUZUMAB IN UNTREATED OLDER PATIENTS (? 70 YEARS OF AGE) WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)

    Purpose: Primary Outcome Measures : Progression-free survival (PFS) [ Time Frame: From randomization date until the earlier of disease progression or death from any cause, assessed up to 10 years ] PFS will be compared between the experimental and control treatment strategy groups using a stratified log-rank test (stratified on Rai stage, intermediate versus [vs.] high, and del(17p13.1) by fluorescence in situ hybridization [FISH], present vs. absent). The Kaplan-Meier method will be used to estimate PFS distributions. Five-year PFS estimates, medians, and corresponding hazard ratios will be provided with 95% confidence intervals for each treatment strategy.

    Secondary Outcome Measures : Bone marrow (BM) minimal residual disease (MRD)- complete response (CR) rate [ Time Frame: Up to 10 years ] BM MRD- CR rate will be calculated and will be estimated using the number of patients meeting the BM MRD- CR criteria divided by the total number of patients randomized to each of the treatment arms. The stratified Cochran-Mantel-Haenszel test will be used to compare the BM MRD- CR rates between treatment arms (stratified on Rai stage, intermediate vs. high, and del(17p13.1) by FISH, present vs. absent).
    Overall survival (OS) [ Time Frame: From randomization date until death from any cause, assessed up to 10 years ] The Kaplan-Meier method will be used to estimate the OS distribution for each treatment strategy. Estimates at 5 years will be calculated with corresponding 95% confidence intervals, and differences in these estimates between the treatment strategies will be tested using a stratified chi-square test based on the complementary log-log transformation of the Kaplan-Meier estimates. Comparisons in OS curves between experimental and control treatment strategies will use a stratified log-rank test (stratified on Rai stage, intermediate vs. high, and del(17p13.1) by FISH, present vs. absent). Hazard ratios with 95% confidence intervals will be estimated from the corresponding, stratified proportional hazard model.
    Incidence of adverse events (AEs) defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment, graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 [ Time Frame: Up to 10 years ] Frequency and severity of adverse events and tolerability for each treatment strategy group will be summarized using descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. The incidence of severe (grade 3+) adverse events or toxicities will be described.

    TRIAL NUMBER: AALL15P1

    Title: A GROUPWIDE PILOT STUDY TO TEST THE TOLERABILITY AND BIOLOGIC ACTIVITY OF THE ADDITION OF AZACITIDINE TO CHEMOTHERAPY IN INFANTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) AND KMT2A (MLL) GENE REARRANGEMENT

    Purpose: Primary Outcome Measures: Incidence of adverse events of azacitidine and combination chemotherapy, graded according to Common Terminology Criteria for Adverse Events 4.0 [ Time Frame: From the first course of azacitidine administration up to fourth course of azacitidine administration ]
    Secondary Outcome Measures: Biologic activity, defined as global DNA methylation change in PBMCs [ Time Frame: Prior to first course of azacitidine up to day 5 of second course of azacitidine ] Will calculate the mean long interspersed nucleotide element-1 (LINE-1) methylation for all patients before and after azacitidine and perform paired t-test analysis to determine if there is significant demethylation in the study population for the tested dose level.

    Other Outcome Measures: EFS [ Time Frame: From time of enrollment up to 5 years ] Descriptive analysis will be conducted to correlate MRD with the EFS for the KMT2A-R patients. PD data for asparaginase activity following pegaspargase administration in infants will be collected and correlated with EFS for the KMT2A-R patients. Standard errors and confidence intervals for EFS will be calculated using Peto's method.
    Expansion of infant T lymphocytes by stimulation with artificial antigen presenting cells [ Time Frame: Up to the end of consolidation therapy, assessed up to 5 years ] Minimal residual disease [ Time Frame: Up to 5 years ] Descriptive analysis will be conducted to correlate MRD with the EFS for the KMT2A-R patients.
    PD data for asparaginase activity following pegaspargase administration [ Time Frame: From 7 days following pegaspargase administration during induction therapy up to 7 days following pegaspargase administration during delayed intensification part 2 ] Will be collected and correlated with EFS for the KMT2A-R patients
    PK parameters of azacitidine [ Time Frame: Pre-dose on days 3 and 4, at 5 and 30 minutes, and 1, 4, and 6 hours post-dose of azacitidine block I ]

    TRIAL NUMBER: AALL1631

    Title: INTERNATIONAL PHASE 3 TRIAL IN PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA (Ph+ ALL) TESTING IMATINIB IN COMBINATION WITH TWO DIFFERENT CYTOTOXIC CHEMOTHERAPY BACKBONES

    Purpose: Primary Outcome Measures : DFS [ Time Frame: Up to 3 years ] Will compare the DFS of standard risk Ph+ ALL patients treated continuous imatinib mesylate with high risk COG/BFM ALL chemotherapy backbone or more intensive EsPhALL chemotherapy backbone.

    Secondary Outcome Measures : DFS of high risk pediatric Ph+ ALL patients treated with EsPhALL chemotherapy, HSCT in first complete remission, and post-HSCT imatinib mesylate [ Time Frame: Up to 3 years ] The 3-year DFS for these patients will be estimated with a maximum standard error of 0.053.
    Imatinib mesylate administration after allogeneic HSCT in high risk Ph+ ALL patients [ Time Frame: Up to 2 years ] Feasibility of post-HSCT imatinib mesylate is determined based on the proportion of patients who receive at least 75% of intended doses.
    Incidence of grade 3 or higher infections in standard risk Ph+ ALL patients in the two randomized arms evaluated according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 3 years ] The rate of infections during the post IB/pre-maintenance phases of treatment will be compared accounting for follow-up time.

    Other Outcome Measures: Adherence to imatinib mesylate after allogeneic HSCT in high risk Ph+ ALL patients [ Time Frame: Up to 12 months post-HSCT ] Longitudinal binomial regression will be conducted using generalized estimating equation methods by modeling monthly adherence rate as an unstructured mean model using five indicator variables of time for the study months. Time in months will also be treated as a continuous variable to explore temporal trends in adherence rate. Compound symmetry will be assumed as the working correlation matrix over time. Covariates that will be considered for adjustment include those hypothesized to be predictors of adherence, annual household income, parental education, time since start of maintenance, risk
    Adherence to oral chemotherapeutic agents in standard risk Ph+ ALL patients [ Time Frame: Up to day 168 of maintenance phase ] Adherence to imatinib mesylate, 6-mercaptopurine, and methotrexate will be evaluated in COG-enrolled participants using an electronic monitoring device. Adherence rate will be computed for each month of adherence monitoring. Longitudinal binomial regression will be conducted using generalized estimating equation methods by modeling monthly adherence rate as an unstructured mean model using five indicator variables of time for the study months. Time in months will also be treated as a continuous variable to explore temporal trends in adherence rate. Compound symmetry will be assumed as the work
    Frequency of p210 BCR-ABL1 fusion variants [ Time Frame: Up to 2 years ] For both SR and HR risk groups, frequencies and prognostic significance (OS, DFS) will be explored for p210 BCR-ABL1 fusion variants in pediatric Ph+ ALL.
    IKZF1 gene aberrations and deletions [ Time Frame: Up to 2 years ] For both SR and HR risk groups, frequencies and prognostic significance (OS, DFS) will be explored for IKZF1 gene aberrations and deletions.
    Incidence of long-term toxicities in patients treated with chemotherapy plus imatinib mesylate (no transplant) in both arms evaluated according to NCI CTCAE version 4.0 [ Time Frame: Up to 3 years ] Frequencies of long-term toxicities will be described and differences between randomized arms will be explored. Specific long-term toxicities to be explored include cardiac (echocardiographic abnormalities, including decreased left ventricular (LV) function and decreased LV wall thickness), growth (linear height, bone age), and second malignant neoplasm.
    Incidence of toxicities associated with post-HSCT administration of imatinib mesylate evaluated according to NCI CTCAE version 4.0 [ Time Frame: Up to 1 year post-HSCT ] Frequencies of target toxicities in HR patients after the initiation of post-HSCT imatinib mesylate will be described. For the HR patients, the specific targeted toxicities will include grade 4 neutropenia, grade 4 thrombocytopenia, grade 3 or higher bilirubin, grade 4 or higher transaminitis, and grade 3 or higher infection.
    MRD assessments made by IGH-TCR PCR assay and NGS assay [ Time Frame: Up to 2 years ] Concordance of MRD assessments made by IGH-TCR PCR assay and NGS assay will be described and evaluated. Scatter plots and diagrams will be used to examine agreements and patterns of agreement or any differences found. Concordance will be explored both for the overall cohort, as well as by risk group. The increased sensitivity of the NGS will be closely examined to find cases where the MRD levels are detectable by NGS but undetectable by PCR, as well as cases in which one test yields results and the other does not (test failure). Prognostic relationships on outcomes for these subjects will be i
    MRD in HR patients measured by IGH-TCR PCR and NGS assay [ Time Frame: Up to 12 months post-HSCT ] The outcome of HR patients will be described, including proportion of patients who achieve MRD-negativity just prior to HSCT, and at regular intervals post-HSCT. Associations between these findings and long-term outcomes (e.g., OS, DFS) will be explored.
    MRD in SR patients measured by IGH-TCR PCR and NGS assay [ Time Frame: Up to 2 years ] The proportion of patients with detectable MRD will be described, and association between MRD levels at later time points and long-term outcomes (e.g., DFS and OS) will be explored. The proportion of SR patients in each of the randomized arms at each of the time points who are not MRD-negative (i.e., MRD non-detectable), or who revert to MRD-positive (i.e., MRD value >= 5 x 10^-4) after previously attaining MRD-negative status will also be explored. Odds ratio estimates comparing the rates of not being MRD-negative at start of delayed intensification phase or MRD-positive at any subsequent mon
    MRD measured by IGH-TCR PCR and NGS assay [ Time Frame: At the end of induction IA ] For both SR and HR risk groups, frequencies and prognostic significance (overall survival [OS], DFS) will be explored for MRD negativity (< 5 x 10^-4) at end of Induction IA.

    TRIAL NUMBER: AAML1531

    Title: RISK-STRATIFIED THERAPY FOR ACUTE MYELOID LEUKEMIA IN DOWN SYNDROME

    Purpose: PRIMARY OBJECTIVES:
    I. To determine the 2-year event-free-survival (EFS) for children with standard risk Down syndrome (DS) acute myeloid leukemia (AML) (minimal residual disease [MRD]-negative after one cycle of induction therapy) after elimination of high dose (HD) Ara-C (cytarabine) from the treatment regimen.
    II. To determine the 2-year EFS for children with high risk DS AML (MRD-positive after one cycle of induction therapy) after intensification of treatment equivalent to that used for high risk AML in children without DS.
    EXPLORATORY OBJECTIVES:
    I. To determine the extent to which elimination of HD Ara-C from the treatment of standard risk DS AML decreases adverse events and resource utilization.
    II. To determine if elimination of HD Ara-C from treatment of standard risk DS AML results in a significant decrease in the number of days per patient spent on protocol therapy compared to predecessor study AAML0431.
    III. To determine if elimination of HD Ara-C from treatment of standard risk DS AML results in a significant decrease in the average number of days of hospitalization per patient compared to predecessor studies AAML0431 and A2971.
    IV. To determine if elimination of HD Ara-C from treatment of standard risk DS AML results in a significant decrease in the number (per patient) and rate (per duration of treatment) of sterile site infections compared to the predecessor study AAML0431.
    V. To determine if elimination of HD Ara-C from treatment of standard risk DS AML results in a significant decrease of resource utilization by AML treatment compared to the predecessor study AAML0431.
    VI. To compare the feasibility and analytical characteristics of flow cytometry, polymerase chain reaction (PCR) and targeted error-corrected sequencing of GATA binding protein 1 (globin transcription factor 1) (GATA1) mutations as methods to detect MRD in DS AML.
    VII. To establish a DS AML cell bank of viably frozen bone marrow samples collected at the end of induction and corresponding non-tumor deoxyribonucleic acid (DNA) samples collected at end of Induction 1.
    OUTLINE:
    INDUCTION I: Patients receive cytarabine intrathecally (IT) on day 1 and intravenously (IV) continuously over 96 hours, daunorubicin hydrochloride IV over 1-15 minutes, and thioguanine orally (PO) twice daily (BID) on days 1-4. Induction I continues for a minimum of 28 days.
    Patients are assigned to 1 of 2 treatment arms based on their MRD status after completion of Induction I.
    ARM A (STANDARD RISK):
    INDUCTION II: Patients receive cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV over 1-15 minutes, and thioguanine PO BID on days 1-4. Induction II continues for a minimum of 28 days.
    INDUCTION III: Patients receive cytarabine, daunorubicin hydrochloride, and thioguanine as in Induction II. Induction III continues for a minimum of 28 days.
    INTENSIFICATION I: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 60-120 minutes on days 1-3. Intensification I continues for a minimum of 28 days.
    INTENSIFICATION II: Patients receive cytarabine and etoposide as in Intensification I. Intensification II continues for a minimum of 28 days.
    ARM B (HIGH RISK):
    INDUCTION II: Patients receive high dose cytarabine IV over 1-3 hours BID on days 1-4 and mitoxantrone hydrochloride IV over 15-30 minutes on days 3-6. Induction II continues for a minimum of 28 days.
    INTENSIFICATION I: Patients receive high dose cytarabine IV over 1-3 hours BID and etoposide IV over 60-120 minutes on days 1-5. Intensification I continues for a minimum of 28 days.
    INTENSIFICATION II: Patients receive high dose cytarabine IV over 3 hours BID on days 1, 2, 8, and 9. Patients also receive asparaginase or asparaginase Erwinia chrysanthemi (E. carotovora) intramuscularly (IM) or IV over 30 minutes on days 2 and 9. Intensification II continues for a minimum of 28 days.
    After completion of study treatment, patients are followed up at 1 month, monthly for 12 months, every 3 months for 12 months, every 6 months for 3 years, annually for 5 years, and then at relapse.

    TRIAL NUMBER: ACCL16N1CD

    Title: Documentation and Delivery of Guideline-Consistent Treatment in Adolescent and Young Adult (AYA) Acute Lymphoblastic Leukemia (ALL)

    Purpose: This research trial studies cancer care delivery in adolescent and young adult patients with acute lymphoblastic leukemia. Surveying institutions, evaluating delivery of care at the patient level and seeking input from healthcare providers may help doctors increase rates of adherence to National Comprehensive Cancer Network (NCCN) treatment guidelines. It may also improve care for adolescent and young adult patients with acute lymphoblastic leukemia.
    PRIMARY OBJECTIVES:
    I. To evaluate the proportion of adolescent and young adult (AYA) acute lymphoblastic leukemia (ALL) patients with a documented treatment plan consistent with NCCN guidelines for AYAs with ALL.
    II. To evaluate the proportion of AYA ALL patients whose delivered treatment during induction and post-induction therapy (PIT) is consistent with NCCN guidelines for AYAs with ALL.
    III. To determine the impact of treating physician specialty and facility type on likelihood of AYA ALL patients having a documented treatment plan concordant with NCCN guidelines when stratified by age group (15-17year[y], 18-21y, and 22-39y).
    IV. To determine the impact of treating physician specialty and facility type on the likelihood of AYA ALL patients receiving induction and post-induction therapy (PIT) concordant with NCCN guidelines when stratified by age group (15-17y, 18-21y, and 22-39y).
    V. To identify for AYAs with ALL, targetable structure- and process-level barriers and facilitators which will increase the proportion of patients having a documented treatment plan and receiving treatment according to NCCN guidelines.
    SECONDARY OBJECTIVES:
    I. To explore potential correlations with clinical and social demographic variables to the presence of a documented treatment plan and delivered treatment consistent with NCCN guidelines in AYAs with ALL.
    OUTLINE:
    CHART REVIEW: Patient medical record data is abstracted and treatment plans are reviewed for consistency to NCCN guidelines. For each patient, induction and post-induction care is recorded as either concordant with NCCN guidelines or non-concordant with NCCN guidelines.
    SITE QUESTIONNAIRE: Participating sites complete a questionnaire which is designed to capture facility-oriented data.
    FOCUS GROUPS: Healthcare providers participate in focus groups over 1-2 hours to discuss facilitators and barriers to AYA ALL guideline concordance. Participants provide responses via electronic handheld technology in order to maintain anonymity followed by discussion of the ideas for clarification.

    TRIAL NUMBER: E1910

    Title: A Phase III Randomized Trial of Blinatumomab for Newly Diagnosed BCR-ABL-Negative B Lineage Acute Lymphoblastic Leukemia in Adults

    Purpose: This randomized phase III trial studies combination chemotherapy with blinatumomab to see how well it works compared to induction chemotherapy alone in treating patients with newly diagnosed breakpoint cluster region (BCR)-c-abl oncogene 1, non-receptor tyrosine kinase (ABL)-negative B lineage acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as blinatumomab, may block cancer growth in different ways by targeting certain cells. It is not yet known whether combination chemotherapy is more effective with or without blinatumomab in treating newly diagnosed acute lymphoblastic leukemia.

    TRIAL NUMBER: EA9161

    Title: A RANDOMIZED PHASE III STUDY OF THE ADDITION OF VENETOCLAX TO IBRUTINIB AND OBINUTUZUMAB VERSUS IBRUTINIB AND OBINUTUZUMAB IN UNTREATED YOUNGER PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)

    Purpose: Primary Outcome Measures : Progression-free survival [ Time Frame: Time from randomization to progression or death without documented progression, assessed up to 10 years ] The analysis will be performed using the repeated confidence intervals methodology. At each interim or final analysis, two-sided repeated confidence interval will be constructed using the partial likelihood estimate from stratified Cox proportional hazards model and the critical value based on the Lan-DeMets error-spending function that corresponds to the truncated O'brien-Fleming boundaries.

    Secondary Outcome Measures : Overall survival [ Time Frame: Time from randomization to death due to any cause, assessed up to 10 years ] A hierarchical testing strategy will be used. The analysis will be performed using the repeated confidence intervals methodology. At each interim or final analysis, two-sided repeated confidence interval will be constructed using the partial likelihood estimate from stratified Cox proportional hazards model and the critical value based on the Lan-DeMets error-spending function that corresponds to the truncated O'brien-Fleming boundaries.
    Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events version 5.0 [ Time Frame: Up to 10 years ]
    Other Outcome Measures: Quality of life (QOL) assessed using Functional Assessment of Cancer Therapy-General (FACT-G) and the leukemia sub-scale [ Time Frame: Baseline up to 10 years ] Linear mixed effects models will be used to perform repeated measures regression analysis. Will compare treatment toxicity-related QOL between the two arms. The entire FACT-Leukemia instrument (FACT-G and the leukemia subscale) at baseline will be analyzed using descriptive statistics to assess the impact of chronic lymphocytic leukemia on QOL independent of treatment.
    FACT-Leu Trial Outcome Index (TOI) score over time [ Time Frame: Baseline up to 10 years ] Will use linear mixed effects models will be used to perform repeated measures regression analysis to examine the treatment effect and time effect on FACT-Leu TOI score.
    Adherence defined as patients taking 80% or more of their prescribed doses [ Time Frame: Baseline up to 10 years ] The ASK-12 Survey will be used to measure the likelihood that a patient will take prescribed medications for patients on both arms at baseline and on day 1 +/- 4 days of the following cycles 3, 7, 15, at the time of response evaluation (end of cycle 19), every 6 months for 2 years post response evaluation, at 48 months after randomization, and at time of disease progression. Descriptive statistics will be used to summarize trend in adherence to prescription.

    TRIAL NUMBER: AHEP1531

    Title: Pediatric Hepatic Malignancy International Therapeutic Trial (PHITT)

    Purpose: Primary Outcome Measures : Event-free survival (EFS) [ Time Frame: From date of randomization until progression of existing disease or occurrence of disease at new sites, death from any cause prior to disease progression, or diagnosis of a second malignant neoplasm, assessed up to 5 years ] Descriptive analysis for each non-randomized and randomized question (by treatment arm and overall) will include: the number (and proportion) of each failure event and in total, survival curves will be estimated by the method of Kaplan-Meier, EFS estimates at 3 and 5 years with 95% confidence intervals (CI), median EFS with CI will be reported if appropriate. A Cox proportional hazards model with EFS as an outcome measure and treatment and stratification factors as covariates will be constructed. This model will be used in the context of a Bayesian analysis and a log Hazard Ratio (HR) will be derived. Bayesian Normal-Normal conjugate analysis of the data will be used to compare treatments. The analysis will use non-informative prior to represent no information about prior beliefs regarding relative treatment difference.
    Response in hepatocellular carcinoma (HCC), defined as complete (CR) or partial (PR) response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria [ Time Frame: Up to 5 years ] The main analysis will be based on a log-binomial model for a Bernoulli response variable. This model will be used in the context of a Bayesian analysis. A non-informative null centered proper prior distributions for the parameters will be used. Response rate (RR) and 95% credible interval (CrI) will be presented. Posterior probabilities for the pre-specified values of interest will be provided. Additionally, the posterior probabilities of RR being larger than 0.7, 0.8, 0.9, 1, 1.1, 1.2 and 1.3 will be also provided.

    Secondary Outcome Measures : Failure free survival [ Time Frame: From date of randomization until the date of first documented progression, date of death from any cause, diagnosis of a second malignant neoplasm or failure to go to resection, whichever came first, assessed up to 5 years ] Descriptive analysis for each non-randomized and randomized question (by treatment arm and overall) will include: the number (and proportion) of each failure event and in total, survival curves will be estimated by the method of Kaplan-Meier. Bayesian Normal-Normal conjugate analysis of the data will be used to compare treatments. The analysis will use non-informative prior to represent no information about prior beliefs regarding relative treatment difference.
    Overall survival [ Time Frame: From date of randomization (or registration for non-randomized patients) until the date of death from any cause, assessed up to 5 years ] Incidence of adverse events [ Time Frame: Up to 5 years ] Will be categorized and graded using Common Terminology Criteria for Adverse Events (CTCAE).
    Chemotherapy-related cardiac, nephro- and oto-toxicity [ Time Frame: Up to 5 years ] Will be recorded in relation to each cycle of treatment and will be categorized and graded using Common Terminology Criteria for Adverse Events.
    Hearing loss measured according to the SIOP Boston Scale for oto-toxicity [ Time Frame: Up to 5 years ] Descriptive analysis for each non-randomized and randomized question (by treatment arm and overall) will include: the number (and proportion) of patients at each the SIOP Boston Scale for oto-toxicity category (i.e. grade 0 to grade 4) and the number (and proportion) of patients who are not assessable for this outcome, (i.e. because of early stopping of treatment, additional treatments to protocol treatment, progression prior to the response assessment or death). The number (and proportion) of patients experiencing any grade hearing loss. Grades 1 to grade 4 will be combined in this analysis. The above will be presented for each assessment time point (EOT and at least 1 year and 2 years of follow up).
    Best response defined as compete response (CR) or partial response (PR) based on radiological response (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) and AFP decline [ Time Frame: Up to 5 years ] Descriptive analysis for each non-randomized and randomized question (by treatment arm and overall) will include: best response will be calculated by taking best RECIST category (i.e. CR, PR, stable disease [SD], progressive disease [PD]) for each patient. CR and PR patients will then be grouped into responders. The number (and proportion) of patients at each best response RECIST category (i.e. CR, PR, SD, PD) and the number (and proportion) of patients who are not assessable for response, e.g. because of early stopping of treatment, progression prior to the response assessment or death. The number (and proportion) of responders (CR and PR) and non-responders.
    Surgical resectability defined as complete resection, partial resection or transplant following randomization (or enrollment for non-randomized patients) [ Time Frame: Up to 5 years ] Descriptive analysis for each non-randomized and randomized question (by treatment arm and overall) will include: The number (and proportion) of patients undergoing complete resection, partial resection or transplant. Time to complete resection, partial resection or transplant following randomization (or enrollment for non-randomized patients) will be analyzed using the Kaplan-Meier method.
    Adherence to surgical guidelines defined as the local clinician?s surgical decision to resect or not compared to the current SIOPEL surgical guidelines [ Time Frame: Up to 5 years ] Descriptive analysis for each non-randomized and randomized question (by treatment arm and overall) will include: The number (and proportion) of patients at each combination of SIOPEL surgical guideline (to resect or not) and local clinician?s surgical decision. The degree of agreement will be measured by Cohen?s kappa with CI.

    TRIAL NUMBER: R1112

    Title: RANDOMIZED PHASE III STUDY OF SORAFENIB VERSUS STEREOTACTIC BODY RADIATION THERAPY FOLLOWED BY SORAFENIB IN HEPATOCELLULAR CARCINOMA

    Purpose: PRIMARY OBJECTIVES:
    I. To determine if stereotactic body radiation therapy (SBRT) improves overall survival in hepatocellular carcinoma (HCC) patients treated with sorafenib (sorafenib tosylate).
    SECONDARY OBJECTIVES:
    I. To determine the difference in time to progression (TTP) and progression- free survival (PFS) in HCC patients treated with sorafenib compared to SBRT followed by sorafenib.
    II. To measure differences in toxicity in HCC patients treated with sorafenib versus SBRT followed by sorafenib.
    III. To measure vascular thrombosis response post sorafenib versus SBRT followed by sorafenib.
    IV. To measure differences in health related quality of life (QOL) and quality- adjusted survival in HCC patients treated with sorafenib compared to SBRT followed by sorafenib.
    V. Collection of biospecimens for future correlative studies to investigate differences in potential biomarkers in patients treated with sorafenib versus SBRT followed by sorafenib.
    OUTLINE: Patients are randomized to 1 of 2 treatment arms.
    ARM 1: Patients receive sorafenib tosylate orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.
    ARM 2: Patients undergo SBRT every 24-72 hours for a total of 5 fractions over 5 to 15 days. Within 1-5 days post-SBRT, patients receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.
    Patients are followed weekly during SBRT, monthly during sorafenib tosylate and on the following schedule as a whole from study entry: every 3 months for 3 years, then every 6 months for 2 years and then annually.

    TRIAL NUMBER: A151216

    Title: Genetic Testing For Patients with Resectable or Resected Lung Cancer: Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST)

    Purpose: PRIMARY OBJECTIVES:
    I. To centrally genotype resected lung adenocarcinomas for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements to facilitate accrual to randomized adjuvant studies.
    II. To obtain clinically annotated tumor tissue and patient-matched non-malignant deoxyribonucleic acid (DNA) from peripheral blood, as well as detailed epidemiologic and clinical follow-up data, to allow clinically annotated advanced genomic analyses in concert with the National Cancer Institute (NCI) Center for Cancer Genomics (CCG).
    SECONDARY OBJECTIVES:
    I. To characterize the natural history of EGFR and ALK wild-type lung cancers to allow subsequent development of targeted therapies against genotype-defined sub-populations in the adjuvant and recurrent settings.
    II. To cross-validate local genotyping assays for EGFR and ALK with a central reference standard.
    TERTIARY OBJECTIVES:
    I. To study the genomic evolution of lung cancers by comparing genomic characteristics at resection and at recurrence.
    OUTLINE:
    Patients undergo collection of blood and tissue samples for EGFR and ALK testing via direct sequencing and fluorescence in situ hybridization (FISH). Patients that have had surgery prior to pre-registration will submit samples from the previous surgery for testing.
    After completion of study, patients that are not enrolled on either A081105 or E4512 are followed up every 6 months for 5 years.

    TRIAL NUMBER: E4512

    Title: A Phase III Double-Blind Trial for Surgically Resected Early Stage Non-Small Cell Lung Cancer: Crizotinib versus Placebo for Patients with Tumors Harboring the Anaplastic Lymphoma Kinase (ALK) Fusion Protein

    Purpose: PRIMARY OBJECTIVES:
    I. To evaluate whether adjuvant therapy with crizotinib will result in improved overall survival (OS) over placebo for patients with stage IB >= 4 cm, II and IIIA, anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) following surgical resection.
    SECONDARY OBJECTIVES:
    I. To evaluate and compare disease-free survival (DFS) associated with crizotinib and placebo.
    II. To evaluate the safety profile of crizotinib when given in the adjuvant therapy setting.
    III. To collect tumor tissue and blood specimens for future research.
    OUTLINE: Patients are randomized to 1 of 2 treatment arms.
    ARM A: Patients receive crizotinib orally (PO) twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
    ARM B: Patients receive placebo PO BID on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
    After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly for 5 years.

    TRIAL NUMBER: LungMAP

    Title: LungMAP: A MASTER PROTOCOL TO EVALUATE BIOMARKER-DRIVEN THERAPIES AND IMMUNOTHERAPIES IN PREVIOUSLY-TREATED NON-SMALL CELL LUNG CANCER (Lung-MAP Screening Study)

    Purpose: 1.1 Primary Objective of the Master Protocol (LungMAP) The primary objective of this screening study is to test patient specimens to determine eligibility for participation in the biomarker-driven and non-matched sub-studies included within the Lung-MAP umbrella protocol. 1.2 Secondary Objectives a. Screening Success Rate Objective To evaluate the screen success rate defined as the percentage of screened patients that register for a therapeutic sub-study. Screen success rates will be evaluated for the total screened population and by the subset of patients screened following progression on previous therapy or pre-screened on current therapy. b. Translational Medicine Objectives 1. To evaluate circulating tumor DNA (ctDNA) and compare to the FMI Foundation tissue molecular profiling results in patients who submit a new biopsy for screening. 2. To establish a tissue/blood repository

    TRIAL NUMBER: NRG-LU005

    Title: Limited Stage Small Cell Lung Cancer (LS-SCLC): A Phase II/III Randomized Study of Chemoradiation Versus Chemoradiation Plus Atezolizumab

    Purpose: Primary Outcome Measures :
    Progression-free survival (PFS) (Phase II) [ Time Frame: Time from randomization to any documented progression or death due to any cause, whichever occurs first, assessed up to 5 years ] Progressive disease (PD) will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will compare the distributions of PFS between treatment arms using a one-sided stratified log-rank test in all randomized eligible patients. The rates at various timepoints (e.g., every 6 months after randomization) and medians of PFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95% confidence interval (CI) will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Results from an unstratified analysis will also be provided.
    Overall survival (OS) (Phase III) [ Time Frame: Time from randomization to the date of death due to any cause, assessed up to 5 years ] The primary hypotheses for the phase II and III portions will be evaluated by comparing arm 1 to arm 2 based on PFS (phase II) and OS (phase III) using a stratified log-rank test. Hazard ratios will be estimated using a stratified Cox regression model. Event rates over time will be estimated within each treatment group using the Kaplan-Meier method.

    Secondary Outcome Measures :
    PFS (phase III) [ Time Frame: Time from randomization to any documented progression or death due to any cause, whichever occurs first, assessed up to 5 years ] The primary hypotheses for the phase II and III portions will be evaluated by comparing arm 1 to arm 2 based on PFS (phase II) and OS (phase III) using a stratified log-rank test. Hazard ratios will be estimated using a stratified Cox regression model. Event rates over time will be estimated within each treatment group using the Kaplan-Meier method.
    Incidence of adverse events [ Time Frame: Up to 5 years ] For each patient, the maximum severity reported for both immune mediated and non-immune mediated adverse events will be used in the summaries. Adverse events will be summarized regardless of relationship to protocol treatment as assessed by the investigator. All adverse events, adverse events leading to withdrawal, interruption or modification of protocol treatment, Grade >= 3 adverse events, and serious adverse events will be summarized. Deaths and cause of death will be summarized. The rate of treatment-related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE, v.5.0) will be reported with the frequency and severity (e.g., type, grade, and attribution) by arm, the analysis will be performed at the time of both phase II and phase III (if applicable) primary endpoint analyses. All adverse events will be classified as either immune or non-immune mediated.
    Objective response rate (ORR) [ Time Frame: Up to 5 years ] Will be defined as the proportion of all randomized subjects whose best overall response (BOR) is either a complete response (CR) or partial response (PR) per RECIST 1.1 criteria. ORR will be compared using a two-sided 5% level Cochran-Mantel Haenszel (CMH) test stratified by the same stratification factors used for randomization. An associated odds ratio and 95% CI will be calculated. The ORR and its corresponding 95% exact CI will also be calculated by Clopper-Pearson for each treatment arm. The difference in ORR between the two treatment arms along with the two-sided 95% CI will be estimated using the following CMH method of weighting, adjusting for the stratification factors.
    Local control [ Time Frame: Up to 5 years ] Will be defined as freedom from local progression, in which a failure is defined as intrathoracic tumor progression by RECIST 1.1 criteria. Local control will be analyzed as competing risks data based on cause-specific hazards approaches, where deaths without local failure will be considered as a competing event and analyzed as "censoring" of local failure. The rates at various timepoints (e.g., every 6 months after randomization) and medians of PFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95% CI will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Results from an unstratified analysis will also be provided.
    Distant metastases-free survival (DMFS) [ Time Frame: Time between the date of randomization and the first date of documented distant metastases or death due to any cause, whichever occurs first, assessed up to 5 years ] Will compare the distributions of DMFS between treatment arms using a one-sided stratified log-rank test in all randomized eligible patients. The rates at various timepoints (e.g., every 6 months after randomization) and medians of DMFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95% CI will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Results from an unstratified analysis will also be provided.
    Quality of life (QoL) [ Time Frame: Up to 15 months after the end of the 4th cycle of chemotherapy ] Will be measured by the Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI). Fisher's exact test will be used to compare the proportions of patients experiencing clinically meaningful deterioration (CMD) between the two arms. FACT-TOI deterioration rates and associated 95% confidence interval will be calculated for each treatment group, based on all randomized subjects. Clopper-Pearson method will be used for calculating 95% CI. The deterioration rates of each arm will also be compared using the CMH test, stratified by histology. FACT-TOI at baseline and at each subsequent assessment, as well as their change from baseline will be summarized using descriptive statistics by treatment group as randomized. The scores at baseline and subsequent time points, as well the changes from baseline at each time point for each treatment group will be compared using the two-sample t-test.
    Quality-adjusted survival [ Time Frame: Up to 2 years ] Assessed using score from the 5-level EuroQol 5-dimensional questionnaire (EQ-5D-5L). Defined as the weighted sum of different time episodes added up to a total quality-adjusted life-year. Subjects' overall health state on a visual analog scale (VAS) at each assessment time point will be summarized using descriptive statistics by treatment group, as randomized. Proportion of subjects reporting problems for the five EQ-5D-5L dimensions at each assessment time point will be summarized by level of problem and by treatment group, as randomized. Percentages will be based on number subjects assessed at assessment time point. Subjects' overall health state on a visual analog scale (EQ-VAS) at each assessment time point will be summarized using descriptive statistics by treatment group, as randomized. Proportion of subjects reporting problems for the five EQ-5D dimensions at each assessment time point will be summarized by level of problem and by treatment group, as randomized.
    Level of fatigue [ Time Frame: Up to 2 years ] Will be measured by the Patient-Reported Outcomes Measurement Information System (PROMIS). Baseline and PROMIS at each subsequent assessment, as well as their change from baseline will be summarized using descriptive statistics by treatment group as randomized. The change from baseline to subsequent timepoints may be compared between treatment arms using a t-test, or Wilcoxon test if the data is non-normal.
    Blood based tumor mutational burden (bTMB) and tissue-based tumor mutational burden (tTMB) [ Time Frame: Up to 5 years ] Correlation with clinical outcomes will be done by summarizing the statistical power to detect interaction effects (ratio of hazard ratios) of 0.33 when the marker positive prevalence is 20%, at 2-sided significance level of 0.05.

    Other Outcome Measures:
    Patient-reported symptomatic toxicities [ Time Frame: Up to 15 months after completion of chemoradiation therapy ] Will be measured by Patient Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE). For each symptom and each domain (i.e., frequency, severity, and interference), counts and frequencies will be summarized for the worst score experienced by the patient by treatment arm.

    TRIAL NUMBER: S1800A

    Title: Ramucirumab and Pembrolizumab Versus Standard of Care in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer (A Lung-MAP Non-Match Treatment Trial)

    Purpose: This phase II Lung-MAP non-Match treatment trial studies how well ramucirumab and pembrolizumab work versus standard of care in treating patients with non-small cell lung cancer that is stage IV or has come back. Immunotherapy with monoclonal antibodies, such as ramucirumab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in standard of care chemotherapy for non-small cell lung cancer, such as docetaxel, gemcitabine hydrochloride, and pemetrexed, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ramucirumab and pembrolizumab together may work better in treating patients with non-small lung cancer compared to standard of care.

    TRIAL NUMBER: EA4181

    Title: A RANDOMIZED 3-ARM PHASE II STUDY COMPARING 1.) BENDAMUSTINE, RITUXIMAB AND HIGH DOSE CYTARABINE (BR/CR) 2.) BENDAMUSTINE, RITUXIMABM HIGH DOSE CYTARABINE AND ACALABRUTINIB (BR/CR-A), AND 3.) BENDUMUSTINEM RITUXIMAB AND ACALABRUTINIB (BR0A) IN PATIENT

    Purpose:

    Primary Outcome Measures :
    1. Composite of positron emission tomography (PET)/computed tomography (CT) complete response (CR) and peripheral blood (PB) minimal residual disease (MRD) negative rate [ Time Frame: Up to 8 weeks post treatment ]
      MRD status is defined as positive, negative, or indeterminate as measured from PB specimens following completion of treatment. Measures of frequencies and proportion, and location and dispersion will be used to describe categorical, and continuous variables respectively; 90% confidence intervals around these estimates will be computed. Kaplan-Meier method will be used to describe time-to-event endpoints and log-rank test to assess difference in time-to-event endpoints by levels of a categorical predictor. Cox proportional hazards (PH) regression model would be used to model the impact of baseline and other relevant variables on time-to-event endpoints.


    Secondary Outcome Measures :
    1. Progression-free survival (PFS) [ Time Frame: From randomization to earliest of disease progression or death, assessed at 36 months ]
    2. Incidence of adverse events [ Time Frame: Up to 10 years post randomization ]
      Assessed by Common Terminology Criteria for Adverse Events (CTCAE). The cumulative dose of high dose cytarabine and proportion of patients that discontinued treatment due to toxicity will be assessed.

    3. Objective response rate (ORR) [ Time Frame: Up to 10 years post randomization ]
      ORR is defined as the proportion of patients achieving a best response to treatment of complete response (CR) or partial response (PR). ORR and PET/CT CR will be estimated in each treatment arm in the efficacy population, as well as among all treated patients, regardless of informative tissue status.

    4. Overall survival (OS) [ Time Frame: From randomization to death, assessed at 36 months ]
      Patients that are alive will be censored at the time of last follow-up. OS will be described using the Kaplan-Meier method and log-rank test will be used to compare survival by treatment arm.

    5. Mobilization failure rate [ Time Frame: Up to 10 years post randomization ]
      Defined as a yield < 2 x10^6 CD34+ stem cells/kg with a maximum of 4 course of apheresis will be summarized as a categorical variable, and compared, between treatment arms using Z- test.


    Other Outcome Measures:
    1. PET/CT negative rate between the three arms [ Time Frame: Up to 10 years post randomization ]
    2. PET quantitative assessment (qPET) [ Time Frame: At end of treatment (within 6 months after the "8 weeks post treatment" timeframe) ]
      Will evaluate the association between baseline qPET and MRD status.

    3. Change of qPET parameters [ Time Frame: Baseline to end of treatment (within 6 months after the "8 weeks post treatment" timeframe) ]
      Will evaluate the association between the change of qPET parameters and MRD and compare this association across all 3 arms.

    4. Incremental prognostic value of baseline qPET to standard risk markers (Mantle Cell Lymphoma International Prognostic Index [MIPI]) [ Time Frame: At end of treatment (within 6 months after the "8 weeks post treatment" timeframe) ]
      Will assess the incremental prognostic value of baseline to standard risk markers (MIPI) in predicting MRD status.

    5. Interim PET status [ Time Frame: At end of treatment (within 6 months after the "8 weeks post treatment" timeframe) ]
      Interim PET status both qualitatively (Deauville) and quantitatively will be correlated with MRD status. Will fit a logistic regression model to evaluate this aim with binary MRD status at end of treatment (EOT) as the response variable and interim PET status as the predictor.

    6. Incremental prognostic value of interim qPET to standard risk markers (MIPI) [ Time Frame: At end of treatment (within 6 months after the "8 weeks post treatment" timeframe) ]
      Will assess the incremental prognostic value of interim qPET to standard risk markers (MIPI) in predicting MRD status.

    7. Incremental prognostic value of interim qPET to Ki67 [ Time Frame: At end of treatment (within 6 months after the "8 weeks post treatment" timeframe) ]
      Will assess the incremental prognostic value of interim qPET to Ki67 in predicting MRD status.

    8. Incremental prognostic value of baseline qPET to Ki67 [ Time Frame: At end of treatment (within 6 months after the "8 weeks post treatment" timeframe) ]
      Will assess the incremental prognostic value of baseline qPET to Ki67 in predicting MRD status.

    TRIAL NUMBER: S1608

    Title: RANDOMIZED PHASE II TRIAL IN EARLY RELAPSING OR REFRACTORY FOLLICULAR LYMPHOMA

    Purpose: Primary Outcome Measures: Complete response (CR) [ Time Frame: Up to 6 courses ] Will be assessed.

    Secondary Outcome Measures: Duration of response (complete response, partial response) [ Time Frame: Up to 5 years ] Will be calculated using the method of Kaplan-Meier.
    Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 5 years ] Toxicity rates can be estimated to within at least ± 15% with 95% confidence.
    M7-LIPI model validation [ Time Frame: Up to 5 years ] The Cox proportional hazards model will be used to assess the association of the m7-FLIPI with to PFS.
    Non-invasive genotyping and circulating tumor deoxyribonucleic acid (DNA) assessment [ Time Frame: Up to 5 years ] Sensitivity, specificity, positive predictive value, negative predictive value, and kappa coefficient will be used to evaluate the concordance. Will evaluate the association of detection of active lymphoma by positron emission tomography-computed tomography and the detection of circulating tumor DNA in plasma at baseline, after 6 and 12 cycles, and at 30 months after initiation of study therapy. Chi-square test will be used to evaluate the association and odds ratio will be calculated.
    Overall survival [ Time Frame: Up to 5 years ] Will be calculated using the method of Kaplan-Meier. 95% confidence for the survival estimates will be constructed using the method of Brookmeyer-Crowley. With 45 eligible patients in each arm, overall survival (OS) at a particular time point, and the 30-month sustained response rate can be estimated to within at least ± 15% with 95% confidence
    Progression-free survival [ Time Frame: From date of registration to date of first observation of progressive disease, or death due to any cause, assessed up to 5 years ] Will be calculated using the method of Kaplan-Meier. 95% confidence for the survival estimates will be constructed using the method of Brookmeyer-Crowley. With 45 eligible patients in each arm, progression free survival (PFS) at a particular time point, and the 30-month sustained response rate can be estimated to within at least ± 15% with 95% confidence

    Estimated Enrollment: 150 Actual Study Start Date: August 10, 2017 Estimated Study Completion Date: December 31, 2022 Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

    TRIAL NUMBER: EA6134

    Title: A Randomized Phase III Trial of Dabrafenib + Trametinib Followed by Ipilimumab + Nivolumab at Progression vs. Ipilimumab + Nivolumab Followed by Dabrafenib + Trametinib at Progression in Patients With Advanced BRAFV600 Mutant Melanoma

    Purpose: This randomized phase III trial studies how well initial treatment with ipilimumab and nivolumab followed by dabrafenib and trametinib works and compares it to initial treatment with dabrafenib and trametinib followed by ipilimumab and nivolumab in treating patients with stage III-IV melanoma that contains a mutation known as v-raf murine sarcoma viral oncogene homolog B V600 (BRAFV600) and cannot be removed by surgery. Ipilimumab and nivolumab may block tumor growth by targeting certain cells. Dabrafenib and trametinib may block tumor growth by targeting the BRAFV600 gene. It is not yet known whether treating patients with ipilimumab and nivolumab followed by dabrafenib and trametinib is more effective than treatment with dabrafenib and trametinib followed by ipilimumab and nivolumab.

    TRIAL NUMBER: A031102

    Title: A RANDOMIZED PHASE III TRIAL COMPARING CONVENTIONAL-DOSE CHEMOTHERAPY USING PACLITAXEL, IFOSFAMIDE, AND CISPLATIN (TIP) WITH HIGH-DOSE CHEMOTHERAPY USING MOBILIZING PACLITAXEL PLUS IFOSFAMIDE FOLLOWED BY HIGH-DOSE CARBOPLATIN AND ETOPOSIDE (TI-CE) AS FIRST SALVAGE TREATMENT IN RELAPSED OR REFRACTORY GERM CELL TUMORS

    Purpose: The study is an international collaboration with European sites. Collaborators on the study include the National Cancer Institute, the European Organization for Research and Treatment of Cancer and the Movember Foundation. Randomization will be stratified by region (North America and Europe) and by modified IPFSG (International Prognostic Factor Study Group) risk classification (low, intermediate and high). The primary and secondary objectives are described below.
    Primary Objective:
    1. To compare the overall survival in patients treated with conventional-dose chemotherapy using the TIP regimen with high-dose chemotherapy (HDCT) plus autologous stem cell transplant (ASCT) using the TI-CE regimen as initial salvage treatment of patients with relapsed or refractory germ cell tumors (GCT)
    Secondary Objectives: 1.To compare the progression-free survival (PFS) of patients treated with initial salvage HDCT with TI-CE versus initial salvage CDCT with TIP 2.To compare the favorable response rate (FRR) of patients treated with initial salvage HDCT with TI-CE versus initial salvage CDCT with TIP 3.To compare the toxicity, including treatment-related mortality, associated with high-dose chemotherapy and ASCT using TI-CE compared with conventional-dose chemotherapy using TIP as initial salvage treatment for patients with relapsed or refractory GCT 4.To prospectively evaluate the IPFSG scoring system as a predictor of outcome to initial salvage therapy in patients with relapsed or refractory GCT. In this trial, randomization will be stratified by a modification of their IPFSG category and we will prospectively evaluate whether or not actual outcomes vary by risk group in the appropriate manner (low risk patients have higher OS than high-risk group). 5.To evaluate the association between tumor marker decline rates of Alpha-Fetoprotein (AFP) and Human Chorionic Gonadotropin (HCG) with OS and PFS.
    Treatment is to continue until disease progression, unacceptable toxicity or completion of all protocol treatment.

    TRIAL NUMBER: ABTR04B1

    Title: ESTABLISHING CONTINUOUS CELL LINES AND XENOGRAFTS FROM PEDIATRIC CANCERS FOR BIOLOGICAL AND PRE-CLINICAL THERAPEUTIC STUDIES

    Purpose: OBJECTIVES: ?Establish and bank cell lines and/or xenografts from pediatric patients with cancer. ?Establish continuous cell lines, under carefully controlled conditions, from pediatric patients with cancer. ?Establish transplantable xenografts in immunocompromised mice from tumor cells that are difficult to establish as continuous cell lines in vitro. ?Create a bank of cell lines and generate sufficient vials of cryopreserved cells for distribution to investigators with approved COG biology protocols. ?Characterize cell lines from childhood cancers with respect to DNA short tandem repeat molecular profile as a "fingerprint" of original cell line identity. ?Characterize cell lines for the ability for sustained growth in tissue culture and/or as mouse xenografts. ?Characterize cell lines for mycoplasma contamination. ?Characterize cell lines for expression of molecular makers that confirm the tumor-type of the cell line and the immortal nature of the cells (telomerase) and the expression of molecular markers that may correlate with drug resistance.
    OUTLINE: This is a multicenter study. Specimens are stratified according to disease (acute lymphoblastic leukemia vs acute myeloid leukemia vs lymphoma vs osteogenic sarcoma vs Ewing family of tumors vs rhabdomyosarcoma vs primitive neuroectodermal tumor vs glioma vs astrocytoma vs rhabdoid tumors vs hepatoblastoma vs retinoblastoma vs Wilms tumor vs germ cell tumors vs other diagnoses).
    Leftover tissue from diagnostic procedures and/or surgery is cryopreserved and banked. Blood and/or bone marrow are also collected and banked.
    Cell lines are established and characterized via reverse-transcriptase polymerase chain reaction and/or flow cytometry for biomarkers and by DNA fingerprinting.
    Markers to be identified may include the following: ?Neuroblastoma: tyrosine hydroxylase, protein gene product (PGP) 9.5, GD2, HLA class I, and HSAN 1.2 antigens ?Ewing family of tumors: EWS-FLI1, EWS-ERG, and PGP 9.5 ?Retinoblastoma: interphotoreceptor retinoid-binding protein ?Acute lymphoblastic leukemia: immunophenotype ?Alveolar rhabdomyosarcoma: PAX3-FKHR, PAX7-FKHR, and MyoD1 ?All cell types: telomerase expression including hTR and hTERT Mutations of TP53 gene are detected by flow cytometry and/or immunocytochemistry.
    No results of these tests are provided to the patient, the patient's physician, or the patient's medical records.
    PROJECTED ACCRUAL: A total of 500 specimens per stratum will be accrued for this study.

    TRIAL NUMBER: AGCT1531

    Title: A PHASE 3 STUDY OF ACTIVE SURVEILLANCE FOR LOW RISK AND A RANDOMIZED TRIAL OF CARBOPLATIN VS. CISPLATIN FOR STANDARD RISK PEDIATRIC AND ADULT PATIENTS WITH GERM CELL TUMORS

    Purpose: Primary Outcome Measures:
    EFS [ Time Frame: The time from study entry to the date of death, date of disease progression or recurrence, date of second malignant neoplasm or date of last contact and ascertained as alive, whichever comes first, assessed up to 5 years ] Overall survival (OS) [ Time Frame: The time from randomization to date of date of death or date of last follow-up and ascertained as alive, assessed up to 8 years ] A 1-sided lower 85% confidence limit for the 2-year survival will be constructed, and if this confidence limit is greater than 0.95, it will be concluded that the strategy provides sufficient OS.

    Secondary Outcome Measures:
    Content validity and understandability of AYA-Hearing Screen assessed by questionnaire [ Time Frame: Baseline ] Incidence of ototoxicity [ Time Frame: 4 weeks after the last dose of platin therapy ] Will compare the proportion of patients who demonstrate hearing loss according to the International Society of Pediatric Oncology criteria.
    Novel genetic variants associated with an increased risk of platinum-associated ototoxicity as determined by standard audiology [ Time Frame: Up to 10 years ] For each candidate gene, will perform an exact two-sided test for the equality of binomial proportions for the event - patient has the candidate gene. The two groups compared will be defined by the presence of SHL. Will use the Bonferroni correction to control experiment-wise error and designate the result as significant if the observed p-value is less than or equal to 0.0025.
    Utility of the 4-miRNA panel as markers diagnostic of MGCTs [ Time Frame: Up to 10 years ] Will use categorical data methods and estimate the probability of demonstrating an elevated miRNA value as the proportion of patients who have the particular miRNA elevated.
    Utility of the 4-miRNA panel as markers diagnostic of MGCTs [ Time Frame: Up to 10 years ] Will compare the diagnostic sensitivity of serum markers, particularly elevated alpha-fetoprotein, to that of elevated microRNA for each of the microRNAs, as well as the characteristic any microRNA elevated. Will perform McNemar's test. The result for each serum evaluation (elevated or not elevated) for each sample on which both serum marker and microRNA evaluation are obtained will be cross tabulated and the p-value associated with McNemar's test calculated. A p-value of 0.05 or less will be considered evidence of differential sensitivity.

    Other Outcome Measures:
    Activation of protein signaling pathway [ Time Frame: Up to 10 years ] Will assess the relationship between pathway activation, including EGFR, MAP Kinase and P3K and risk for disease progression. Tumor materials will be evaluated for the activation of specific pathways, including the three mentioned above. The effect of pathway activation, coded as yes vs. no, on the cause-specific hazard of EFS component disease progression will be estimated by relative risk regression considering other EFS events as censoring events. Will use the Benjamini and Hochberg procedure to control the false discovery rate.
    Binomial data [ Time Frame: Up to 10 years ] Will use repeated measures binomial data as the initial approach to investigating this exploratory aim. Each biomarker will be examined individually. The predictor variables will be the measured value of particular novel biomarker and randomized treatment regimen. The response variable will be the occurrence of grade 3 or higher nephrotoxicity during the next treatment cycle. Will use logistic regression with a shared random frailty for outcomes for the same individual, when the subject's biomarkers are evaluated more than once during protocol therapy and the particular toxicity type is revers
    Incidence of kidney dysfunction [ Time Frame: 12-16 weeks after the last dose of platin therapy ] Two patient characteristics will be used to measure kidney dysfunction: (1) the presence of Grade 1 or greater elevation of serum creatinine; and a second measure that is more sensitive for damage to the renal endothelium (2) albuminuria.
    Incidence of self-reported peripheral neuropathy assessed by the 11-item Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity scale [ Time Frame: Up to 12 months ] Will compare the characteristics obtained at the start of chemotherapy of patients from the relevant groups who contribute to the patient reported outcome analyses with those who do not to investigate whether the measured group may not be representative of the study population. Will also conduct other sensitivity analysis as appropriate to assess the effects of missing data on the analysis for this aim.
    Incidence of self-reported peripheral neuropathy assessed by the 11-item Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity scale [ Time Frame: Up to 12 months ] Will compare self-reported peripheral neuropathy and other patient-reported outcomes between children, adolescents and young adults with standard risk germ cell tumors treated with carboplatin-based chemotherapy as compared to cisplatin based chemotherapy.
    Prognostic effects of the marker defined by microRNA signature present or high values of alpha-fetoprotein or beta-HCG [ Time Frame: Up to 10 years ] Will be assessed using a proportional approach. EFS from time of enrollment will be used for markers that are obtained at enrollment. EFS post complete evaluation of marker decline will be used for markers where the characteristic is the change in a putative marker.
    Prognostic significance of the 4-miRNA panel [ Time Frame: Up to 10 years ] Will be assessed using time-dependent covariate analysis.

    TRIAL NUMBER: AGCT1532

    Title: Phase 3 Accelerated BEP Trial: A randomised phase 3 trial of accelerated versus standard BEP chemotherapy for patients with intermediate and poor-risk metastatic germ cell tumours

    Purpose: The purpose of this study is to determine whether accelerated BEP chemotherapy is more effective than standard BEP chemotherapy in males with intermediate and poor-risk metastatic germ cell tumours.
    Bleomycin, Etoposide, Cisplatin (BEP) administered 3-weekly x 4 remains standard 1st line chemotherapy for intermediate- and poor-risk metastatic germ cell tumours (GCTs). Cure rates are over 90% for good-risk disease, 85% with intermediate-risk, and about 70% for poor-risk disease. Previous strategies to improve first-line chemotherapy have failed to improve cure rates and were more toxic than BEP. New strategies are needed for patients with intermediate and poor-risk disease. BEP is accelerated by cycling Cisplatin and etoposide 2-weekly instead of 3-weekly. The Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) is conducting a trial comparing accelerated BEP with standard BEP. The aim of this study is to determine if accelerated BEP is superior to standard BEP as first-line chemotherapy for intermediate and poor risk metastatic GCTs.

    TRIAL NUMBER: ALTE05N1

    Title: Umbrella Long-Term Follow-Up Protocol

    Purpose: OBJECTIVES:
    ?To develop a mechanism for tracking and retaining patients enrolled on COG protocols. ?To maintain regular, lifetime contact with patients in order to obtain current identification and contact information, and self/parent-reported health status. ?To locate patients who are lost-to-follow-up for COG (or Legacy Group) protocols targeted for follow-up by the Long-Term Follow-Up Center (LTFC). ?To provide current patient contact information and self/parent-reported health status updates to the COG Statistics and Data Center (SDC) and to each patient's COG institution. ?To facilitate collection of protocol-specific outcome data through collaboration with the COG Late Effects Committee, the SDC, and the member institutions. ?To collect cumulative therapeutic exposure data (via therapeutic summaries completed online by treating institutions) on patients completing active therapy. OUTLINE: This is an umbrella protocol for all long-term follow-up at COG institutions. Approximately 6 months after completion of therapy patients receive a mailed packet introducing the Long-Term Follow-Up Center (LTFC) and containing information related to their individualized, protocol-specific follow-up guidelines. Patients are asked to complete a patient response form, verify information provided in packet, update contact information, and complete a Health Status Update Form. The Health Status Update Form is a brief document including questions about current health status, disease status, and cancer therapy received since the last mailing. Patients receive protocol-specific automatic reminders, and may respond by use of postage prepaid envelopes, email, or 24-hour toll-free telephone.

    TRIAL NUMBER: APEC1621A

    Title: Pediatric MATCH: Trk Inhibitor LOXO-101 in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions

    Purpose: This phase II trial studies Trk inhibitor LOXO-101 in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with NTRK fusions that have spread to other places in the body and have come back or do not respond to treatment. Trk inhibitor LOXO-101 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth

    TRIAL NUMBER: APEC1621B

    Title: Pediatric MATCH: Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations

    Purpose: This phase II trial studies how well erdafitinib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders that have spread to other places in the body and have come back or do not respond to treatment with FGFR mutations. Erdafitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621C

    Title: Pediatric MATCH: Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations

    Purpose: This phase II trial studies how well tazemetostat works in treating patients with solid tumors, non-hodgkin lymphoma, or histiocytic disorders that have spread to other places in the body and have come back or do not respond to treatment and have EZH2, SMARCB1, or SMARCA4 gene mutations. Tazemetostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621D

    Title: Pediatric MATCH: PI3K/mTOR Inhibitor LY3023414 in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations

    Purpose: This phase II trial studies how well PI3K/mTOR inhibitor LY3023414 works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with TSC or PI3K/MTOR mutations that have spread to other places in the body and have come back or do not respond to treatment. PI3K/mTOR inhibitor LY3023414 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621E

    Title: Pediatric MATCH: Selumetinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating MAPK Pathway Mutations

    Purpose: This phase II trial studies how well selumetinib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with MAPK pathway activation mutations that have spread to other places in the body and have come back or do not respond to treatment. Selumetinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621F

    Title: Pediatric MATCH: Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations

    Purpose: This phase II trial studies how well ensartinib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with ALK or ROS1 genomic alterations that have come back or do not respond to treatment and have spread to other places in the body. Ensartinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621G

    Title: Pediatric MATCH: Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations

    Purpose: This phase II trial studies how well vemurafenib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with BRAF V600 mutations that have spread to other places in the body and have come back or do not respond to treatment. Vemurafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621H

    Title: Pediatric MATCH: Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes

    Purpose: This phase II trial studies how well olaparib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with defects in deoxyribonucleic acid (DNA) damage repair genes that have spread to other places in the body and have come back or do not respond to treatment. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    TRIAL NUMBER: APEC1621SC

    Title: Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders

    Purpose: This screening and multi-sub-study phase II trial studies how well treatment that is directed by genetic testing works in pediatric patients with solid tumors, non-Hodgkin lymphomas, or histiocytic disorders that have progressed following at least one line of standard systemic therapy and/or for which no standard treatment exists that has been shown to prolong survival. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic changes or abnormalities (mutations) may benefit more from treatment which targets their tumor's particular genetic mutation, and may help doctors plan better treatment for patients with solid tumors or non-Hodgkin lymphomas.

    TRIAL NUMBER: EAY131

    Title: EAY131: Molecular Analysis for Therapy Choice (NCI-MATCH)

    Purpose: This phase II trial studies how well treatment that is directed by genetic testing works in patients with solid tumors or lymphomas that have progressed following at least one line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment which targets their tumor's particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors or lymphomas.

    TRIAL NUMBER: S1609

    Title: SWOG 1609: DART: Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors Treatment with Ipilimumab and Nivolumab for Rare Cancers

    Purpose: Both Ipilimumab and Nivolumab have already been FDA-approved to treat other cancers. However, Ipilimumab and Nivolumab are investigational and not FDA-approved for use in combination in treating rare cancers or cancers of unknown primary origin.

    TRIAL NUMBER: EAA173

    Title: DARATUMUMAB TO ENHANCE THERAPEUTIC EFFECTIVENESS OF REVLIMID IN SMOLDERING MYELOMA (DETER-SMM)

    Purpose: Primary Outcome Measures :
    Overall survival (OS) [ Time Frame: From randomization to death due to any cause, or censored at date last known alive, assessed up to 15 years ] Will be estimated using the Kaplan-Meier (KM) method and compared using a stratified log-rank test. Stratified cox proportional hazards regression will produce a treatment hazard ratio estimate.
    Functional Assessment of Cancer Therapy-General (FACT-G) score [ Time Frame: Baseline to 24 cycles of treatment (each cycle is 28 days) ] A general effect size measure of half standard deviation will be used to establish the minimally important difference. Descriptive statistics (mean, standard deviation [SD], median, range) will be used to evaluate the distribution of levels and changes for the set of health-related quality of life (QOL) evaluations. Levels and changes will also be assessed graphically. Changes from baseline will be analyzed using linear mixed models based on restricted maximum likelihood estimation with covariance matrix maximizing Akaike information criteria. Models with treatment, assessment time, and treatment by assessment time interaction with and without other predictors will be fit. If there is substantial missingness, will analyze the data according to the methods described in Schluchter and Schluchter, Greene and Beck.

    Secondary Outcome Measures :
    Progression-free survival (PFS) [ Time Frame: From randomization until disease progression or death due to any cause, or censored at date of last disease evaluation, assessed up to 15 years ] Will be estimated using the KM method and compared using a stratified log-rank test. Stratified cox proportional hazards regression will produce a treatment hazard ratio estimate.
    Best response on treatment based on International Myeloma Working Group (IMWG) criteria [ Time Frame: At 12 and 24 months ] Response will be tabulated by category. Response rates of very good partial response (VGPR) or better and partial response (PR) or better will be compared using the Fisher's exact test. Ineligible patients are excluded from the analysis and unevaluable patients are counted in the denominator.
    Incidence of adverse events by worst grade and type for treated patients determined using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: Up to 28 days post-treatment ] Will monitor the toxicities experienced by all treated patients. Will compare rates of worst grade 3 or higher non-hematologic treatment-related events using the Fisher's exact test.
    Incidence of grade 3 or higher infusion-related reactions over course 1 determined based on CTCAE [ Time Frame: During cycle 1 of treatment (each cycle is 28 days) ] Will monitor the toxicities experienced by all treated patients. Will compare rates of worst grade 3 or higher non-hematologic treatment-related events using the Fisher's exact test.
    Stem cell (SC) mobilization failure [ Time Frame: After 4 to 6 cycles of treatment (each cycle is 28 days) ] Defined as not collecting a minimum of 5x10^6 CD34 cells per kilogram weight. SC mobilization and type of growth factor support will be summarized overall and by treatment arm with descriptive statistics.
    Early SC mobilization feasibility [ Time Frame: Up to 6 cycles of treatment (each cycle is 28 days) ] Defined as the proportion of patients less than 65 years of age treated for 6 courses who opt for SC mobilization. SC mobilization and type of growth factor support will be summarized overall and by treatment arm with descriptive statistics.
    Type of growth factor support [ Time Frame: During 4 to 6 cycles of treatment (each cycle is 28 days) ] SC mobilization and type of growth factor support will be summarized overall and by treatment arm with descriptive statistics.
    Change in FACT-G score [ Time Frame: From treatment end to 6 months post-treatment ] A general effect size measure of half standard deviation will be used to establish the minimally important difference. Descriptive statistics (mean, SD, median, range) will be used to evaluate the distribution of levels and changes for the set of health-related QOL evaluations. Levels and changes will also be assessed graphically. Changes from baseline will be analyzed using linear mixed models based on restricted maximum likelihood estimation with covariance matrix maximizing Akaike information criteria. Models with treatment, assessment time, and treatment by assessment time interaction with and without other predictors will be fit. If there is substantial missingness, will analyze the data according to the methods described in Schluchter and Schluchter, Greene and Beck.
    Levels of FACT-G score at each assessment time point [ Time Frame: From baseline, at 3, f7, 13, 19 cycles of treatment, and early discontinuation of treatment, assessed up to 24 cycles of treatment (each cycle is 28 days) ] A general effect size measure of half standard deviation will be used to establish the minimally important difference. Descriptive statistics (mean, SD, median, range) will be used to evaluate the distribution of levels and changes for the set of health-related QOL evaluations. Levels and changes will also be assessed graphically. Changes from baseline will be analyzed using linear mixed models based on restricted maximum likelihood estimation with covariance matrix maximizing Akaike information criteria. Models with treatment, assessment time, and treatment by assessment time interaction with and without other predictors will be fit. If there is substantial missingness, will analyze the data according to the methods described in Schluchter and Schluchter, Greene and Beck.
    Time to worsening of FACT-G [ Time Frame: From baseline until a decrease of 9 points, or censored at date of last assessment, assessed up to 6 months post-treatment ] Will be analyzed with Kaplan-Meier methods and Cox regression with the related treatment arm as the only factor. Correlation between time to worsening of symptoms with PFS and OS will be assessed with Kendall's Tau adjusted for censored observations.

    Other Outcome Measures:
    Cumulative dose calculated as the sum of all doses taken across all cycles [ Time Frame: Up to 24 months ] Cumulative dose will be calculated overall and by cycle. Data will be summarized by treatment arm with descriptive statistics and graphically over time. Patients will be classified into dichotomous groups based on a 75% relative dose intensity cutoff (< 75% versus [vs] >= 75% represents poor vs good treatment adherence). The proportion of patients with poor lenalidomide treatment adherence will be compared between arms using the Fisher's exact test. In addition, multi-variable logistic regression analysis will be conducted to identify the baseline factors associated with calculated good treatment adherence.
    Dose intensity calculated as cumulative dose received divided by treatment duration [ Time Frame: Up to 24 months ] Dose intensity will be calculated overall and by cycle. Data will be summarized by treatment arm with descriptive statistics and graphically over time. Patients will be classified into dichotomous groups based on a 75% relative dose intensity cutoff (< 75% vs >= 75% represents poor vs good treatment adherence). The proportion of patients with poor lenalidomide treatment adherence will be compared between arms using the Fisher's exact test. In addition, multi-variable logistic regression analysis will be conducted to identify the baseline factors associated with calculated good treatment adherence.
    Relative dose intensity calculated as the dose intensity divided by planned dose intensity [ Time Frame: Up to 24 months ] Dose intensity will be calculated overall and by cycle. Data will be summarized by treatment arm with descriptive statistics and graphically over time. Patients will be classified into dichotomous groups based on a 75% relative dose intensity cutoff (< 75% vs >= 75% represents poor vs good treatment adherence). The proportion of patients with poor lenalidomide treatment adherence will be compared between arms using the Fisher's exact test. In addition, multi-variable logistic regression analysis will be conducted to identify the baseline factors associated with calculated good treatment adherence.
    Duration of treatment [ Time Frame: From randomization to date off treatment, or censored at the date of last treatment, assessed up to 24 months ] Treatment duration in each arm will be estimated using Kaplan-Meier methods and compared between arms with the log-rank test.
    Time to progression [ Time Frame: From randomization to progression, or censored at date of last disease evaluation, assessed up to 15 years ] Will be estimated using the Kaplan-Meier method.
    Presence, frequency, interference, amount and/or severity of select patient reported outcomes (PRO)-CTCAEs [ Time Frame: Assessed at each treatment cycle, from cycle 1 of treatment to end of treatment, up to 24 cycles of treatment (each cycle is 28 days) ] Descriptive statistics (mean, standard deviation, median, range) will be used to summarize selected PRO-CTCAEs tabulated at each cycle overall and by arm. Will map PRO-CTCAEs with provider reported adverse events (AEs) and evaluate differences in incidence and worst severity. Items correspond to 5 attributes measured [frequency (F), severity (S), interference (I), presence/absence (P) and amount (A)] based on multiple choice questions. Response for each attribute except P which is binary is on a 5-point Likert scale with 5 indicating 'almost constantly' frequency, 'very severe' severity, 'very much' amount or 'very much' interference. An overall PRO-CTCAE score will be calculated at each time point.
    Overall PRO-CTCAE score [ Time Frame: Up to 15 years ] Defined as the sum of item scores on all symptomatic adverse events (AEs). Descriptive statistics will be used to summarize selected PRO-CTCAEs tabulated at each cycle overall and by arm. Will map PRO-CTCAEs with provider reported AEs and evaluate differences in incidence and worst severity. An overall PRO-CTCAE score will be calculated at each time point.
    Adherence Starts with Knowledge (ASK)-12 scores [ Time Frame: At 7, 13, and 19 cycles of treatment (each cycle is 28 days) ] Descriptive statistics will be used to summarize ASK-12 scores tabulated at cycles 7, 13 and 19 overall and by arm. Differences between arms will be evaluated based a t-test (or Wilcoxon rank sum test). Patients will also be classified into high versus low likelihood of medication adherence groups according to tertile distributions (lowest tertile vs second and top). Association between likelihood of medication adherence and calculated treatment adherence dichotomous groups will be evaluated in patients with both ASK-12 and treatment data at cycles 7, 13 and 19 post randomization. In addition, multivariable logistic regression analysis will be conducted to identify the baseline factors associated with low likelihood of medication adherence.
    PRO compliance rate [ Time Frame: Up to 15 years ] Defined as the proportion of patients who submit the given PRO instrument among those eligible at each time point which excludes those missing by design (due to death or disease progression, early treatment discontinuation).
    PRO completion rate [ Time Frame: Up to 15 years ] Defined as the proportion of patients who complete given PRO instrument based on the instrument's scoring system among those eligible at each time point.

    TRIAL NUMBER: ANBL1821

    Title: A PHASE 2 RANDOMIZED STUDY OF IRINOTECAN/TEMOZOLOMIDE/DINUTUXIMAB WITH OR WITHOUT EFLORNITHINE (DFMO) (IND#141913) IN CHILDREN WITH RELAPSED, REFRACTORY OR PROGRESSIVE NEUROBLASTOMA

    Purpose:

    Primary Outcome Measures :
    1. Response rate [ Time Frame: Up to the first 6 cycles of treatment ]
      Responders are defined as patients who achieve a >= minor response (MR) per the International Neuroblastoma Response Criteria (INRC) as their best overall response by the end of 6 cycles. The response rate to treatment will be calculated among all eligible patients, including placement of a 95% confidence interval on the response rate.


    Secondary Outcome Measures :
    1. Progression-free survival (PFS) [ Time Frame: Up to 5 years ]
      Kaplan-Meier method will be used to estimate progression-free survival (PFS). PFS time will be calculated from the time of randomization to the occurrence of relapse, progressive disease, or death. Patients without a PFS event will be censored at the time of last follow-up.

    2. Overall survival (OS) [ Time Frame: Up to 5 years ]
      Kaplan-Meier method will be used to estimate overall survival (OS). OS time will be calculated from the time of randomization to the occurrence of death. Patients still alive will be censored at the time of last follow-up.

    3. Incidence of adverse events >= Grade 3 (Regimen B) [ Time Frame: Up to 5 years ]
      The percentage of patients on Regimen B with at least one Grade 3 or higher toxicity will be calculated, assessed with Common Terminology Criteria for Adverse Events version 5.0.


    Other Outcome Measures:
    1. Immune and cytokine profiles [ Time Frame: Up to 6 cycles ]
      Will be assessed by exploring the relationship between response (responder versus [vs.] non-responder) after 6 cycles on Regimen B with serum cytokine levels (IL1, IL6, tumor necrosis factor [TNF]-alpha, IFN-gamma, etc.), tumor resident immune cells (natural killer [NK] cells, tumor-associated macrophages [TAMS], tumor infiltrating lymphocyte [TILS]), and critical immune cell suppressing proteins (B7H3, PDL-1) using Fisher's exact test for categorical and Wilcoxon rank-sum test for continuous factors.

    2. GD2 levels in tumor cells from bone marrow samples [ Time Frame: Up to 5 years ]
      Will be correlated with response (responder vs. non-responder) after 6 cycles using Fisher?s exact test for categorical and the Wilcoxon rank-sum test for continuous factors.

    3. Patient reported pain and opiate usage [ Time Frame: Up to 5 years ]
      The occurrence of pain on each regimen as reported by patient report and opiate use will be descriptively summarized. Descriptive and summary statistics will be used to describe the scores from the Faces Pain Scale-Revised during the dinutuximab infusion and on day 1 with irinotecan and temozolomide alone for each arm separately. Confidence intervals will be constructed for the mean and frequency estimates. The day 1 patient reported outcome data are expected to be similar between the 2 regimens, while differences during or after completion of treatment may be observed.

    TRIAL NUMBER: NRG-GU002

    Title: NRG-GU002: PHASE II-III TRIAL OF ADJUVANT RADIOTHERAPY AND ANDROGEN DEPRIVATION FOLLOWING RADICAL PROSTATECTOMY WITH OR WITHOUT ADJUVANT DOCETAXEL

    Purpose: This randomized phase II/III trial studies docetaxel, antiandrogen therapy, and radiation therapy to see how well it works compared with antiandrogen therapy and radiation therapy alone in treating patients with prostate cancer that has been removed by surgery. Androgen can cause the growth of prostate cells. Antihormone therapy may lessen the amount of androgen made by the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving antiandrogen therapy and radiation therapy with or without docetaxel after surgery may kill any remaining tumor cells.

    TRIAL NUMBER: AREN1721

    Title: A RANDOMIZED PHASE 2 TRIAL OF AXITINIB/NIVOLUMAB COMBINATION THERAPY VS. SINGLE AGENT AXITINIB OR NIVOLUMAB FOR THE TREATMENT OF TFE/TRANSLOCATION RENAL CELL CARCINOMA (tRCC) ACROSS ALL AGE GROUPS

    Purpose:

    Primary Outcome Measures :
    1. Progression free survival [ Time Frame: From initiation of treatment assessed up to 4 years ]

    Other Outcome Measures:
    1. Translocation morphology renal cell carcinoma clinical behavior [ Time Frame: Up to 4 years ]
      Will list and summarize the frequency of site(s) of disease at presentation (including extent of lymph node involvement), site(s) of relapse, surgical practices on protocol therapy, and radiotherapy practices on protocol therapy.

    2. Type of antitumor immune response and stability of T cell activation [ Time Frame: Baseline up to 4 years ]
      Will summarize the levels of analytes and tumor expression before and after treatment and evaluate the changes due to treatment after logarithmic transformation using the paired t-test. Analytes include myeloid derived stem cells: CD45, CD11b, CD33, CD14, CD15, HLA-DR, viability, stain 1; regulatory T cells: viability, CD45, CE4, CD3, CD24, FoxP3; CD8 T cells (CD45, CD8, CD3); CD8 phenotype and activation and exhaustion (CD69, CD38, PD1, CD244, TIM3). Tumor expression of PDL-1, PD1, CD3, CD4 and CD8 will be assessed using TFE renal cell carcinoma samples from the study and scored for intensity (0 - 3).

    TRIAL NUMBER: S1400F

    Title: A PHASE II STUDY OF MEDI4736 (DURVALUMAB) PLUS TREMELIMUMAB AS THERAPY FOR PATIENTS WITH PREVIOUSLY TREATED ANTI-PD-1/PD-L1 RESISTANT STAGE IV SQUAMOUS CELL LUNG CANCER (LUNG-MAP NON-MATCH SUB-STUDY)

    Purpose: Primary Outcome Measures: Investigator-assessed progression-free survival as defined by Response Evaluation Criteria in Solid Tumors 1.1 (Design #1, Phase II) [ Time Frame: From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 18 months since completion of accrual ] A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to investigator-assessed progression-free survival, comparing the two treatment arms.
    Investigator-assessed progression-free survival in patients with advanced stage refractory squamous cell carcinoma of the lung randomized to receive investigational therapy vs standard therapy (Design #2,Phase III,Option for Biomarker-driven sub-studies) [ Time Frame: Up to 3 years ] Estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median investigator-assessed progression-free survival. A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to progression free survival comparing the two treatment arms at the levels specified.
    Less than 33% improvement in median investigator-assessed progression-free survival as defined as Response Evaluation Criteria in Solid Tumors 1.1 (Design #1, Phase III) [ Time Frame: From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 18 months since completion of accrual ] A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to investigator-assessed progression-free survival, comparing the two treatment arms. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.
    Objective response rate (confirmed and unconfirmed, complete and partial) (Design #2, Phase II, Option for Biomarker-driven Sub-studies) [ Time Frame: Up to 3 years ] The investigational therapy arm will be judged to have provided sufficient evidence to proceed to the Phase III component if the objective response rate is at least 25%. Response rates and associated confidence intervals will be calculated.
    Objective response rate (confirmed and unconfirmed, complete and partial) in patients treated with investigational non-match therapy with advanced stage refractory squamous cell carcinoma of the lung (Design #2, Option for Non-Match Sub-Studies) [ Time Frame: Up to 3 years ] Response rates and associated confidence intervals will be calculated.
    Overall survival (Design #1, Phase III) [ Time Frame: From date of sub-study registration (or date of screening registration if patient never enrolls in a sub-study) to date of death due to any cause, assessed up to 3 years ] A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to overall survival, comparing the two treatment arms. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.
    Overall survival in patients with advanced stage refractory squamous cell carcinoma of the lung randomized to receive investigational therapy versus standard therapy (Design #2, Phase III, Option for Biomarker-driven Sub-studies) [ Time Frame: Up to 3 years ] The Brookmeyer-Crowley method will be used to calculate confidence intervals for median overall survival. A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to overall survival comparing the two treatment arms at the levels specified.

    Secondary Outcome Measures: Duration of response among patients who achieve a complete response or partial response by Response Evaluation Criteria in Solid Tumors 1.1 (Design #2, Phase II, Option for Biomarker-driven Sub-studies and Design #2, Option for Non-Match Sub-studies) [ Time Frame: Up to 3 years ] Estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median duration of response.
    Frequency and severity of toxicities associated with investigational therapy versus standard therapy (Design #2, Phase III, Option for Biomarker-driven Sub-studies) [ Time Frame: Up to 3 years ] Analysis of toxicities will be performed using a chi-square or Fisher?s exact test, as appropriate.
    Investigator-assessed progression-free survival, censoring patients with symptomatic deterioration at the time of symptomatic deterioration (Design #1, Phase III) [ Time Frame: From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 3 years ] Descriptive data will be presented.
    Overall survival with investigational therapy (Design #2, Phase II, Option for Biomarker-driven Sub-studies and Design #2, Option for Non-Match Sub-studies) [ Time Frame: Up to 3 years ] A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to overall survival comparing the two treatment arms at the levels specified. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.
    Progression free survival with investigational therapy (Design #2, Phase II, Option for Biomarker-driven Sub-studies and Design #2, Option for Non-Match Sub-studies) [ Time Frame: Up to 3 years ] A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to progression free survival comparing the two treatment arms at the levels specified. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.
    Response rate (confirmed and unconfirmed) in patients with measurable disease as defined by Response Evaluation Criteria in Solid Tumors 1.1 (Design #1, Phase II and III) [ Time Frame: Up to 3 years ] Analysis will be performed using a chi squared or Fisher?s exact test, as appropriate. Response proportions will be compared using a 1-sided Fisher?s exact test at the 0.001 level.
    Response rates (confirmed and unconfirmed, complete and partial) among patients randomized to receive investigational therapy versus standard therapy (Design #2, Phase III, Option for Biomarker-driven Sub-studies) [ Time Frame: Up to 3 years ] Analysis of response rates will be performed using a chi-square or Fisher?s exact test, as appropriate.
    Severity of toxicities associated with investigational therapy versus standard therapy (Design #2, Phase II, Option for Biomarker-driven Sub-studies and Design #2, Option for Non-Match Sub-studies) [ Time Frame: Up to 3 years ] Analysis of toxicities will be performed using a chi-square or Fisher?s exact test, as appropriate.
    Toxicity frequencies, monitored using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Design #1, Phase II and III) [ Time Frame: Up to 3 years ] Analysis will be performed using a chi squared or Fisher?s exact test, as appropriate.

    Other Outcome Measures: Screen success rate, monitored by the percentage of screened patients that register to a therapeutic sub-study [ Time Frame: Up to 3 years ] Descriptive data will be presented.
    Treatment arm randomization acceptance rate, monitored by the percentage of patients that receive at least one dose of the treatment they are randomized to (Design #1) [ Time Frame: Up to 3 years ] Descriptive data will be presented.

    Estimated Enrollment: 10000 Actual Study Start Date: June 16, 2014 Estimated Study Completion Date: April 1, 2022 Estimated Primary Completion Date: April 1, 2022 (Final data collection date for primary outcome measure)

    TRIAL NUMBER: APEC1621J

    Title: NCI-COG PEDIATRIC MATCH (MOLECULAR ANALYSIS FOR THERAPY CHOICE)- PHASE 2 SUBPROTOCOL OF BVD-523FB (ULIXERTINIB) IN PATIENTS WITH TUMORS HARBORING ACTIVATING MAPK PATHWAY MUTATIONS

    Purpose: Primary Outcome Measures : Objective response rate (ORR = complete response [CR] + partial response [PR]) in pediatric patients treated with BVD-523FB (ulixertinib) [ Time Frame: Up to 2 years ] Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed using the Wilson score interval method

    Secondary Outcome Measures : Progression free survival (PFS) in pediatric patients treated with ulixertinib [ Time Frame: From initiation of treatment to disease progression, disease recurrence, or death from any cause assessed up to 2 years ] PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.
    Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events version 5.0 [ Time Frame: Up to 2 years ] Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. A patient will be counted only once for a given toxicity for the worst grade of that toxicity reported for that patient. Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen.
    Preliminary estimates of the pharmacokinetics of ulixertinib in children and adolescents with relapsed or refractory cancer [ Time Frame: Pre-dose and 1, 2, 4, and 6-8 hours after dose on course 1, day 1; and pre-dose on course 1, day 2, and course 1, day 15 ] Will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

    Other Outcome Measures: Other biomarkers as predictors of response to ulixertinib and whether tumors that harbor different mutations or fusions will demonstrate differential response to treatment [ Time Frame: Up to 2 years ] Will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.
    Profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA) [ Time Frame: Up to 2 years ] Will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.

    TRIAL NUMBER: A091605

    Title: A RANDOMIZED PHASE II STUDY OF ANTI-PD1 ANTIBODY [MK-3475 (PEMBROLIZUMAB)] ALONE VERSUS ANTI-PD1 ANTIBODY PLUS STEREOTACTIC BODY RADIATION THERAPY IN ADVANCED MERKEL CELL CARCINOMA

    Purpose: This randomized phase II trial studies how well pembrolizumab with or without stereotactic body radiation therapy works in treating patients with merkel cell cancer that has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy is a specialized radiation therapy that sends x-rays directly to the tumor using smaller doses over several days and may cause less damage to normal tissue. Giving pembrolizumab with stereotactic body radiation therapy may work better in treating patients with merkel cell cancer.

    TRIAL NUMBER: A091802

    Title: Phase II Randomized Trial of Avelumab Plus Cetuximab Versus Avelumab Alone in Advanced Cutaneous Squamous Cell Carcinoma of the Skin (cSCC)

    Purpose: This phase II trial studies how well avelumab with or without cetuximab work in treating patients with skin squamous cell cancer that has spread to other places in the body. Immunotherapy with monoclonal antibodies, such as avelumab and cetuximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.


    TRIAL NUMBER: A031501

    Title: PHASE III RANDOMIZED ADJUVANT STUDY OF MK-3475 (PEMBROLIZUMAB) IN MUSCLE INVASIVE AND LOCALLY ADVANCED UROTHELIAL CARCINOMA (AMBASSADOR) VERSUS OBSERVATION

    Purpose: Primary Outcome Measures: Disease-free survival [ Time Frame: From randomization to the first metastatic recurrence (presence of any recurrent disease), or death, whichever occurs first, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.
    Overall survival [ Time Frame: From randomization to the date of death from any cause, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.

    Secondary Outcome Measures: Disease-free survival in PD-L1 positive and negative patients [ Time Frame: From randomization to the first metastatic recurrence (presence of any recurrent disease), or death, whichever occurs first, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.
    Overall survival in PD-L1 positive and negative patients [ Time Frame: From randomization to the date of death from any cause, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.

    Estimated Enrollment: 739 Actual Study Start Date: September 21, 2017 Estimated Study Completion Date: February 28, 2019 Estimated Primary Completion Date: February 28, 2019 (Final data collection date for primary outcome measure)

    • West Jefferson Medical Center
    • Jefferson
    • 5 Trials Available
    • CONTACT US

    TRIAL NUMBER: CG01 GBM

    Title: Standard Chemotherapy versus Chemotherapy Chosen by Cancer Stem Cell Chemosensitivity Testing in the Management of Patients with Recurrent Glioblastoma Multiforme (GBM)

    Purpose:

    The purpose of this clinical study is to confirm the utility of chemosensitivity tumor testing on cancer stem cells (ChemoID) as a predictor of clinical response in poor prognosis malignant brain tumors such as recurrent glioblastoma (GBM).

    This study is designed as a parallel group randomized controlled clinical trial to determine if recurrent Glioblastoma (GBM) patients treated with drugs predicted by the ChemoID assay will have better outcomes than patients treated with standard-of-care control therapy chosen by the Physician.

    Upon obtaining informed consent, all eligible participants affected by recurrent GBM will have a tumor biopsy to undergo ChemoID drug response testing with multiple FDA-approved chemotherapeutic agents.

    Eligible participants will be randomized to a standard treatment arm with control treatment (chemotherapy chosen by the Physician from a provided list), or to a study arm of FDA-approved drugs selected by the ChemoID drug response assay.

    TRIAL NUMBER: N0577

    Title: N0577 (CODEL): Phase III Intergroup Study of Radiotherapy with Concomitant and Adjuvant Temozolomide versus Radiotherapy with Adjuvant PCV Chemotherapy in Patients with 1p/19q Co-deleted Anaplastic Glioma or Low Grade Glioma

    Purpose: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving radiation with concomitant and adjuvant temozolomide versus radiation with adjuvant PCV is more effective in treating anaplastic glioma or low grade glioma.

    TRIAL NUMBER: Southeastern Study of Cancer and the Environment

    Title: Southeastern Study of Cancer and the Environment

    Purpose: STUDY PURPOSE - The purpose of the research is to provide new information on genetic and environmental risk factors for adult-onset glioma and meningioma. Such information is relevant to prevention and treatment. STUDY DESIGN – The study is a multi-institutional, clinic-based case-control study of genetic and environmental risk factors for adult-onset brain tumors (glioma and meningioma). Cases (brain tumor patients) will be identified at leading brain tumor treatment centers and several neurosurgical/neuro-oncology practices in the southeastern US. Community controls will be identified by a survey research firm (SDR Sampling Services - Atlanta, Georgia) with individual matching on age, gender, zipcode and season of enrollment. The second control group, consisting of friends, relatives and other associates of the case, will be matched on age and gender.

    TRIAL NUMBER: WF-1801

    Title: A Single Arm, Pilot Study of Ramipril for Preventing Radiation-Induced Cognitive Decline in Glioblastoma (GBM) Patients Receiving Brain Radiotherapy

    Purpose: This study is to determine if an oral drug called Ramipril can lower the chance of memory loss in patients with glioblastoma getting chemoradiation. Patients will take Ramipril during chemoradiation and continue until 4 months post-treatment. Memory loss will be assessed using several neurocognitive tests throughout the duration of the study.

    TRIAL NUMBER: DCP-001

    Title: DCP-001, Use of a Clinical Trial Screening Tool to Address Cancer Health Disparities in the NCI Community Oncology Research Program (NCORP)

    Purpose: The protocol is not a scientific study; rather, a method to implement the screening tool and allow the collection and analyses of expanded data with informed consent. Investigators also enroll patients into NCI-treatment trials. The tool, based on a screening log successfully used within the NCI Community Cancer Centers Program (NCCCP), has been streamlined and integrated into the sites’ workflow by using OPEN. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. Also missing from the existing data is the context of care, within the communities themselves where most cancer and at risk of cancer patients receive care which is the focus of NCORP. The profile of patients accrued to NCI-sponsored clinical trials lacks both racial/ethnic and socioeconomic diversity. Accrued patients tend to be insured, highly educated and of higher socioeconomic means. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. NCORP's clinical trials portfolio includes cancer control, prevention, screening, symptom science, and cancer care delivery research.

    • Culicchia Neurological Clinic LLC
    • Jefferson
    • 4 Trials Available
    • CONTACT US

    TRIAL NUMBER: CG01 GBM

    Title: Standard Chemotherapy versus Chemotherapy Chosen by Cancer Stem Cell Chemosensitivity Testing in the Management of Patients with Recurrent Glioblastoma Multiforme (GBM)

    Purpose:

    The purpose of this clinical study is to confirm the utility of chemosensitivity tumor testing on cancer stem cells (ChemoID) as a predictor of clinical response in poor prognosis malignant brain tumors such as recurrent glioblastoma (GBM).

    This study is designed as a parallel group randomized controlled clinical trial to determine if recurrent Glioblastoma (GBM) patients treated with drugs predicted by the ChemoID assay will have better outcomes than patients treated with standard-of-care control therapy chosen by the Physician.

    Upon obtaining informed consent, all eligible participants affected by recurrent GBM will have a tumor biopsy to undergo ChemoID drug response testing with multiple FDA-approved chemotherapeutic agents.

    Eligible participants will be randomized to a standard treatment arm with control treatment (chemotherapy chosen by the Physician from a provided list), or to a study arm of FDA-approved drugs selected by the ChemoID drug response assay.

    TRIAL NUMBER: Southeastern Study of Cancer and the Environment

    Title: Southeastern Study of Cancer and the Environment

    Purpose: STUDY PURPOSE - The purpose of the research is to provide new information on genetic and environmental risk factors for adult-onset glioma and meningioma. Such information is relevant to prevention and treatment. STUDY DESIGN – The study is a multi-institutional, clinic-based case-control study of genetic and environmental risk factors for adult-onset brain tumors (glioma and meningioma). Cases (brain tumor patients) will be identified at leading brain tumor treatment centers and several neurosurgical/neuro-oncology practices in the southeastern US. Community controls will be identified by a survey research firm (SDR Sampling Services - Atlanta, Georgia) with individual matching on age, gender, zipcode and season of enrollment. The second control group, consisting of friends, relatives and other associates of the case, will be matched on age and gender.

    TRIAL NUMBER: WF-1801

    Title: A Single Arm, Pilot Study of Ramipril for Preventing Radiation-Induced Cognitive Decline in Glioblastoma (GBM) Patients Receiving Brain Radiotherapy

    Purpose: This study is to determine if an oral drug called Ramipril can lower the chance of memory loss in patients with glioblastoma getting chemoradiation. Patients will take Ramipril during chemoradiation and continue until 4 months post-treatment. Memory loss will be assessed using several neurocognitive tests throughout the duration of the study.

    TRIAL NUMBER: DCP-001

    Title: DCP-001, Use of a Clinical Trial Screening Tool to Address Cancer Health Disparities in the NCI Community Oncology Research Program (NCORP)

    Purpose: The protocol is not a scientific study; rather, a method to implement the screening tool and allow the collection and analyses of expanded data with informed consent. Investigators also enroll patients into NCI-treatment trials. The tool, based on a screening log successfully used within the NCI Community Cancer Centers Program (NCCCP), has been streamlined and integrated into the sites’ workflow by using OPEN. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. Also missing from the existing data is the context of care, within the communities themselves where most cancer and at risk of cancer patients receive care which is the focus of NCORP. The profile of patients accrued to NCI-sponsored clinical trials lacks both racial/ethnic and socioeconomic diversity. Accrued patients tend to be insured, highly educated and of higher socioeconomic means. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. NCORP's clinical trials portfolio includes cancer control, prevention, screening, symptom science, and cancer care delivery research.

    • MBP Cancer Center
    • East Baton Rouge
    • 23 Trials Available
    • CONTACT US

    TRIAL NUMBER: A011202

    Title: A Randomized Phase III Trial Evaluating the Role of Axillary Lymph Node Dissection in Breast Cancer Patients (CT1-3 N1) Who Have Positive Sentinel Lymph Node Disease After Neoadjuvant Chemotherapy

    Purpose: Study Outline: All patients will undergo surgery to identify sentinel lymph node(s). If a lymph node (sentinel or non-sentinel) is determined to be positive on intra-operative pathology the patient will be registered/randomized intra-operatively. Patients who do not have a sentinel lymph node identified will not be registered/randomized to the study. Patients whose sentinel lymph node status is cannot be/is not determined intra- operatively, and have not undergone ALND, but had at least one lymph node (sentinel or non-sentinel) found to be positive on final pathology review will be registered/randomized post-operatively. Patients whose sentinel lymph node status is found to be negative intra-operatively and have not undergone ALND, but had at least one lymph node (sentinel or non-sentinel) found to be positive on final pathology review will be registered/randomized post-operatively. ALND is not to be performed prior to registration/randomization. Patients who are determined to have negative lymph nodes on final pathology will not be registered/randomized, but can be offered participation in another cooperative group trial. The primary and secondary objectives of the study are described below. Please see the "Arms" section for a detailed description of the treatment regimens. Primary Objective: To evaluate whether radiation to the undissected axilla and regional lymph nodes is not inferior to axillary lymph node dissection with radiation to the regional lymph nodes but not to the dissected axilla in terms of invasive breast cancer recurrence-free interval in patients with positive SLN(s) after completion of neoadjuvant chemotherapy Secondary Objectives: To evaluate whether radiation to the undissected axilla and regional lymph nodes is not inferior to axillary lymph node dissection with radiation to the regional lymph nodes but not to the dissected axilla in terms of the incidence of invasive loco-regional recurrences in patients with a positive SLN(s) after completion of neoadjuvant chemotherapy To obtain an estimate of the distribution of residual disease burden scores for each treatment arm To estimate the distribution of overall survival for each treatment arm Patients may receive adjuvant and ancillary therapy as appropriate per the protocol. Adjuvant Therapy: Adjuvant endocrine therapy: Patients with hormone receptor (ER and/or PR) positive disease should receive a minimum of 5 years of standard endocrine therapy (experimental agents/regimens are not permitted). Endocrine therapy should begin following completion of neoadjuvant chemotherapy and surgery, either before, during or after radiation therapy at the discretion of the oncologist. Selection of the agents is at the treating physician's discretion. Patients with HER 2 positive disease should complete a total of one year of trastuzumab therapy (over the neoadjuvant and adjuvant period). Chemotherapy, biologic therapy or vaccine therapy in the adjuvant setting is not allowed. Patients who wish to receive any of these therapies after surgery must go off study at the time of their initiation. Ancillary Therapy: Patients should receive full supportive care, including transfusions of blood and blood products, erythropoetin (unless otherwise specified in the protocol), antibiotics, antiemetics, etc. when appropriate. Patients are followed up for 5 years after completion of radiation therapy.

    TRIAL NUMBER: EA1131

    Title: A Randomized Phase III Post-Operative Trial of Platinum Based Chemotherapy Vs. Observation in Patients with Residual Triple-Negative Basal-Like Breast Cancer following Neoadjuvant Chemotherapy

    Purpose: The purpose of this study is to compare the IDFS in TNBC patients with residual basal-like disease after neoadjuvant chemotherapy who are randomized to post-preoperative platinum based chemotherapy with those who are randomized to observation. At present, upon completion of neoadjuvant therapy, the standard of care for patients with TNBC (who have no clinical evidence of metastatic disease after surgical excision of the cancer regardless of burden of residual disease) is observation, since there is no additional therapies available with proven impact. This study could provide a possible alternative treatment, which makes it appropriate for the population.

    TRIAL NUMBER: EA1151

    Title: Digital Tomosynthesis Mammography and Digital Mammography in Screening Patients for Breast Cancer

    Purpose: This randomized phase III trial studies digital tomosynthesis mammography and digital mammography in screening patients for breast cancer. Screening for breast cancer with tomosynthesis mammography may be superior to digital mammography for breast cancer screening and may help reduce the need for additional imaging or treatment.

    TRIAL NUMBER: NRG-BR003

    Title: A Randomized Phase III Trial of Adjuvant Therapy Comparing Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel With or Without Carboplatin for Node-Positive or High-Risk Node-Negative Triple-Negative Invasive Breast Cancer

    Purpose: This randomized phase III trial studies how well doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel with or without carboplatin work in treating patients with triple-negative breast cancer. Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether doxorubicin hydrochloride and cyclophosphamide is more effective when followed by paclitaxel alone or paclitaxel and carboplatin in treating triple-negative breast cancer.

    TRIAL NUMBER: NRG-BR004

    Title: A Randomized, Double-Blind, Phase III Trial of Paclitaxel/Trastuzumab/Pertuzumab With Atezolizumab or Placebo in First-Line HER2-Positive Metastatic Breast Cancer

    Purpose: his randomized phase III trial studies how well paclitaxel, trastuzumab, and pertuzumab with or without atezolizumab works in treating patients with breast cancer that has spread to other parts of the body. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as trastuzumab, pertuzumab, and atezolizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving paclitaxel, trastuzumab, and pertuzumab with or without atezolizumab may kill more tumor cells.

    TRIAL NUMBER: S1418

    Title: A Randomized, Phase III Trial to Evaluate the Efficacy and Safety of MK-3475 (Pembrolizumab) as Adjuvant Therapy for Triple Receptor-Negative Breast Cancer With ? 1 cm Residual Invasive Cancer or Positive Lymph Nodes (ypN+) After Neoadjuvant Chemotherapy

    Purpose: This randomized phase III trial studies how well pembrolizumab works in treating triple-negative breast cancer. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

    TRIAL NUMBER: URCC-18007

    Title: RANDOMIZED PLACEBO CONTROLLED TRIAL OF BUPROPION FOR CANCER RELATED FATIGUE

    Purpose: AIMS/OBJECTIVES 2.1 Primary Aim is to determine the efficacy of bupropion versus placebo in reducing fatigue in a double-blinded, placebo-controlled, randomized clinical trial of breast cancer survivors with fatigue Primary Hypothesis: Bupropion will be associated with greater improvements in fatigue than placebo. 2.2 Secondary Aim 1 is to assess the efficacy of bupropion versus placebo on depression and quality of life in breast cancer survivors with fatigue Secondary Hypothesis 1a: Bupropion will be associated with greater improvements in depression and quality of life than placebo. Secondary Hypothesis 1b: The beneficial effects of bupropion on fatigue will be independent of its effects on depression. 2.3 Secondary Aim 2 is to assess the tolerability of bupropion in breast cancer survivors with fatigue Secondary Hypothesis 2: Adherence, incidence of CTCAE grade 2 or above toxicity, self-reported insomnia, and early discontinuation will be similar between the bupropion and placebo groups. 2.4 Exploratory Aim 1 is to assess the efficacy of bupropion versus placebo on symptomatology and cognition in breast cancer survivors with fatigue Exploratory Hypothesis 1a: Bupropion will be associated with greater improvements in depression and quality of life than placebo. 2.5 Exploratory Aim 2 is to explore the effects of bupropion on putative mechanisms of cancer-related fatigue Exploratory Hypothesis 2a: The relationship between group assignment and reductions in fatigue will be mediated by cytokines and cortisol slope. Exploratory Hypothesis 2b: The relationship between bupropion metabolites and fatigue in the bupropion group will be mediated by cytokines and cortisol slope. 2.5 Exploratory Aim 3 is to explore associations of CYP2B6 genotype with bupropion metabolism and changes in fatigue Exploratory Hypothesis 3: Bupropion metabolism and improvements in fatigue will be greater in patients with no copies of the reduced-function *6 allele (i.e., normal metabolizers) compared to patients with one or two copies of the *6 allele (i.e., reduced metabolizers). We will also compare associations of CYP2B6 genotype and tolerability. Since little previous data exists on CYP2B6 genotype and bupropion tolerability, no hypotheses are offered.

    TRIAL NUMBER: WF 97116

    Title: Phase 3 Randomized Placebo Controlled Clinical Trial of Donepezil - WF 97116

    Purpose: This study is to compare the safety and effects of donepezil (Aricept) or if it decreases memory loss after receiving chemotherapy for breast cancer.

    TRIAL NUMBER: DCP-001

    Title: DCP-001, Use of a Clinical Trial Screening Tool to Address Cancer Health Disparities in the NCI Community Oncology Research Program (NCORP)

    Purpose: The protocol is not a scientific study; rather, a method to implement the screening tool and allow the collection and analyses of expanded data with informed consent. Investigators also enroll patients into NCI-treatment trials. The tool, based on a screening log successfully used within the NCI Community Cancer Centers Program (NCCCP), has been streamlined and integrated into the sites’ workflow by using OPEN. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. Also missing from the existing data is the context of care, within the communities themselves where most cancer and at risk of cancer patients receive care which is the focus of NCORP. The profile of patients accrued to NCI-sponsored clinical trials lacks both racial/ethnic and socioeconomic diversity. Accrued patients tend to be insured, highly educated and of higher socioeconomic means. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. NCORP's clinical trials portfolio includes cancer control, prevention, screening, symptom science, and cancer care delivery research.

    TRIAL NUMBER: A021502

    Title: Randomized Trial of Standard Chemotherapy Alone or Combined With Atezolizumab as Adjuvant Therapy for Patients With Stage III Colon Cancer and Deficient DNA Mismatch Repair

    Purpose: This randomized phase III trial studies combination chemotherapy and atezolizumab to see how well it works compared with combination chemotherapy alone in treating patients with stage III colon cancer and deficient deoxyribonucleic acid (DNA) mismatch repair. Drugs used in combination chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as atezolizumab, may interfere with the ability of tumor cells to grow and spread. Giving combination chemotherapy with atezolizumab may work better than combination chemotherapy alone in treating patients with colon cancer.

    TRIAL NUMBER: WF-1802

    Title: Influence of Primary Treatment for Prostate Cancer on Work Experience (PCW)

    Purpose: The objective of this study is to examine how adenocarcinoma of the prostate treatment differentially affects African American men's ability to work and to describe and compare changes in work ability (as measured through self-reported global work ability item) reported by African American and white adenocarcinoma of the prostate survivors before treatment and 6 months after treatment completion.

    TRIAL NUMBER: NRG GY003

    Title: Phase II Randomized Trial of Nivolumab With or Without Ipilimumab in Patients With Persistent or Recurrent Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancer

    Purpose: This phase II trial studies how well nivolumab works with or without ipilimumab in treating patients with epithelial ovarian, primary peritoneal, or fallopian tube cancer that has not responded after prior treatment (persistent) or has come back (recurrent). Monoclonal antibodies, such as nivolumab and ipilimumab, may block tumor growth in different ways by targeting certain cells.

    TRIAL NUMBER: NRG-GY009

    Title: RANDOMIZED, PHASE II/III STUDY OF PEGYLATED LIPOSOMAL DOXORUBICIN AND CTEP-SUPPLIED ATEZOLIZUMAB (IND #134427) VERSUS PEGYLATED LIPOSOMAL DOXORUBICIN/BEVACIZUMAB AND CTEP-SUPPLIED ATEZOLIZUMAB VERSUS PEGYLATED LIPOSOMAL DOXORUBICIN/BEVACIZUMAB IN PLATINUM RESISTANT OVARIAN CANCER

    Purpose: Primary Outcome Measures : Incidence of dose limiting toxicities (DLT) of experimental regimens graded using Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.0 [ Time Frame: Up to 28 days ] DLT will be assessed.
    Overall survival (OS) (Phase III) [ Time Frame: From study enrollment to the date of death regardless of the cause, assessed up to 5 years ] OS will be evaluated.
    Progression free survival (PFS) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v.) 1.1 criteria (Phase II) [ Time Frame: From study enrollment to the investigator determined date of progression or death due to any cause, whichever occurs first, assessed up to 5 years ] Estimated using Kaplan-Meier estimates of the treatment-specific cumulative distribution.

    Secondary Outcome Measures : Disease-related symptoms as assessed by the National Comprehensive Cancer Network (NCCN)- Functional Assessment of Cancer Therapy (FACT) ovarian symptom index (NFOSI)-disease-related symptoms (DRS) (Phase II) [ Time Frame: Up to 2 years ] A repeated measures model will be used to estimate and compare the mean DRS-physical (P) scores for the treatment groups. Model covariates will include the patients' randomly assigned study treatment, age at enrollment onto the study, initial performance status, pre-treatment DRS-P score, assessment time and treatment-by-time interaction. The primary analyses will include only those treatments selected at the end of the phase II study and all of the patients assigned to one of these treatments during either stage 2 of the safety lead-in, phase II or phase III component of the study regardless
    Disease-related symptoms as assessed by the National Comprehensive Cancer Network (NCCN)- Functional Assessment of Cancer Therapy (FACT) ovarian symptom index (NFOSI)-disease-related symptoms (DRS) (Phase III) [ Time Frame: Up to 2 years ] A repeated measures model will be used to estimate and compare the mean DRS-physical (P) scores for the treatment groups. Model covariates will include the patients' randomly assigned study treatment, age at enrollment onto the study, initial performance status, pre-treatment DRS-P score, assessment time and treatment-by-time interaction. The primary analyses will include only those treatments selected at the end of the phase II study and all of the patients assigned to one of these treatments during either stage 2 of the safety lead-in, phase II or phase III component of the study regardless
    Frequency and severity of adverse events assessed by CTCAE v. 4.0 (Phase II) [ Time Frame: Up to 5 years ] The maximum grade of each adverse event (AE) by system organ class and Common Toxicity Criteria (CTC) 4.0 specific term will be tabulated for those individuals who at least initiate study treatment. The number and percent of individuals will be tabulated by the maximum grade of their AE.
    Frequency and severity of adverse events assessed by CTCAE v. 4.0 (Phase III) [ Time Frame: Up to 5 years ] The maximum grade of each AE by system organ class and CTC 4.0 specific term will be tabulated for those individuals who at least initiate study treatment. The number and percent of individuals will be tabulated by the maximum grade of their AE.
    Objective response rate (ORR) (partial or complete response) assessed by RECIST version (v.) 1.1 criteria (Phase II) [ Time Frame: Up to 5 years ] Will be tabulated by treatment group, and 95% confidence intervals will be presented using Wilson's Score Method. Treatment arms will be compared using a likelihood ratio chi-square test.
    Objective response rate (ORR) (partial or complete response) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v.) 1.1 (Phase III) [ Time Frame: Up to 5 years ] Will be tabulated by treatment group, and 95% confidence intervals will be presented using Wilson's Score Method. Treatment arms will be compared using a likelihood ratio chi-square test.
    Patient reported outcomes (PRO) as measured by treatment side effects (TSE), function/well-being (FWB), fatigue and health status (Phase II) [ Time Frame: Up to 2 years ] Each of the other general PRO scales will be analyzed with repeated measures models. Exploratory analyses will include an assessment of the model residuals in order to evaluate the adequacy of modeling assumptions. Additional descriptive analyses will assess whether the differences in mean scores between groups vary systematically with time in a linear or quadratic fashion.
    Patient reported outcomes (PRO) as measured by treatment side effects (TSE), function/well-being (FWB), fatigue and health status (Phase III) [ Time Frame: Up to 2 years ] Each of the other general PRO scales will be analyzed with repeated measures models. Exploratory analyses will include an assessment of the model residuals in order to evaluate the adequacy of modeling assumptions. Additional descriptive analyses will assess whether the differences in mean scores between groups vary systematically with time in a linear or quadratic fashion.
    PD-L1 will be assessed in enrolled patients using immunohistochemistry on tumors embedded in paraffin [ Time Frame: Up to 5 years ] The proportion of patients expressing PD-L1 in this patient population will be estimated. A proportional hazards model will be used to estimate the hazard of death for patients who express PD-L1 relative to those who do not express PL-D1 for each treatment group. The homogeneity of these estimated hazard ratios will then be assessed. Its association with the duration of PFS or OS will be determined.
    Progression free survival (PFS) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v.) 1.1 criteria (Phase III) [ Time Frame: From study enrollment to the investigator determined date of progression or death due to any cause, whichever occurs first, assessed up to 5 years ] Estimated using Kaplan-Meier estimates of the treatment-specific cumulative distribution.

    Other Outcome Measures: Changes in quantitative biomarker parameters in tissue, blood, and stool [ Time Frame: Baseline up to 12 weeks ] Changes in quantitative biomarker parameters in tissue, blood, and stool will be assessed.

    TRIAL NUMBER: NRG-HN005

    Title: A RANDOMIZED PHASE II/III TRIAL OF DE-INTENSIFIED RADIATION THERAPY FOR PATIENTS WITH EARLY-STAGE, P16-POSITIVE, NON-SMOKING ASSOCIATED OROPHARYNGEAL CANCER

    Purpose:

    Primary Outcome Measures :
    1. Progression-free survival (PFS) (Phase II) [ Time Frame: Up to 6 years ]
      Will be estimated for all treatment arms using the Kaplan-Meier method (1958). The primary phase IIR endpoint will be tested using a confidence interval (CI) approach.

    2. PFS (Phase III) [ Time Frame: Up to 6 years ]
      Will be estimated for all treatment arms using the Kaplan-Meier method (1958). The co-primary phase III endpoint will be tested using a confidence interval (CI) approach.

    3. Quality of life [ Time Frame: Baseline up to 6 years ]
      Measured by the MD Anderson Dysphagia Inventory (MDADI) global quality of life (QOL) score. Will be compared between arms using a two-sample independent t-test at a one-sided significance level of 0.05 for each experimental arm comparison. MDADI global score and change from baseline will be summarized using mean and standard deviation at each time point for each arm.


    Secondary Outcome Measures :
    1. Locoregional failure [ Time Frame: From the time of randomization to the date of failure, date of precluding event, or last known follow-up date, assessed up to 6 years ]
      The cumulative incidence estimator will be used to estimate time to event distributions for locoregional failure between arm differences tested using cause-specific log-rank test.

    2. Distant failure [ Time Frame: Up to 6 years ]
    3. Overall survival [ Time Frame: From the date of randomization to the date of death or last known follow-up date, with patients alive at the last known follow-up time treated as censored, assessed up to 6 years ]
      Will be estimated using the Kaplan-Meier method and treatment arms compared using the log-rank test (Kaplan 1958).

    4. Incidence of adverse events [ Time Frame: Up to 6 years ]
      Measured by the Common Terminology Criteria for Adverse Events (CTCAE). Adverse events (AEs) will be graded using CTCAE version (v)5.0. Counts of all AEs by grade will be provided by treatment arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm. The number of patients with at least 1 grade 3 or higher AE will be compared between the treatment arms. A comparison between treatment arms of grade 3 and higher AEs related to treatment will also be tested. A comparison of grade 3 and higher events will be compared between treatment arms. All comparisons will be tested using a Chi-Square test, or Fisher's exact test if cell frequencies are < 5, with a significance level of 0.05.

    5. Hearing [ Time Frame: Baseline up to 24 months from end of radiation therapy (RT) ]
      Measured as Hearing Handicap Inventory for Adults-Screening (HHIA-S).

    6. Quality of life [ Time Frame: Baseline up to 24 months from end of RT ]
      Measured by the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire (QLQ)30.

    7. Fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) locoregional control [ Time Frame: Up to 6 years ]
      Will be associated with PFS.

    8. Negative predictive value of post-RT FDG-PET/CT for locoregional control [ Time Frame: At 1 and 2 years ]
      The negative predictive value of FDG-PET/CT for locoregional control will be estimated using binomial proportions and confidence intervals based on normal approximation.

    9. Negative predictive value of post-RT FDG-PET/CT for PFS [ Time Frame: At 1 and 2 years ]
      The negative predictive value of FDG-PET/CT PFS will be estimated using binomial proportions and confidence intervals based on normal approximation.

    10. Incidence of adverse events [ Time Frame: Up to 6 years ]
      Measured using Patient-Reported Outcomes (PRO)-CTCAE. For each symptom, counts and frequencies will be provided for the worst score experienced by the patient by treatment arm. The proportion of patients with scores >= 1 and >= 3 will be compared between groups using a Chi-square test, or Fisher's exact test if cell frequencies are < 5, using a significance level of 0.05. Analysis of changes in patient reported outcomes over time will analyzed by fitting generalized estimating equations (GEE) models using a logit link (dichotomizing the symptom scores as 0 vs. > 1 and 0-2 vs. 3-4) with time of assessment, treatment arm, and treatment-by-time interaction terms in the model.


    Other Outcome Measures:
    1. Quality of life [ Time Frame: Baseline up to 24 months from end of RT ]
      Measured by EuroQol-5 Dimensional- 5 Level (EQ-5D-5L).

    2. Swallowing physiology [ Time Frame: Up to 6 years ]
      Measured by a Modified Barium Swallow (MBS) test. The proportion of aspiration for each arm will be estimated assuming a binomial distribution and between arm comparison will be performed using a Fisher's exact test.

    3. Locoregional control for patients with post-RT FDG-PET/CT [ Time Frame: At 12-14 weeks post-RT ]
      Locoregional control rates will be compared between negative and positive/undetermined patients. Cox proportional hazards models will be used to determine whether there are differences between these two groups, while adjusting for treatment arm and other covariates (cause-specific Cox models for locoregional failure).

    4. PFS for patients with post-RT FDG-PET/CT [ Time Frame: At 12-14 weeks post-RT ]
      PFS rates will be compared between negative and positive/undetermined patients. Cox proportional hazards models will be used to determine whether there are differences between these two groups, while adjusting for treatment arm and other covariates (cause-specific Cox models for locoregional failure).

    TRIAL NUMBER: EA8143

    Title: EA8143:A Phase 3 RandOmized Study Comparing PERioperative Nivolumab vs. Observation in Patients with Localized Renal Cell Carcinoma Undergoing Nephrectomy (PROSPER RCC)

    Purpose: The purpose of this study is to compare any good and bad effects of using nivolumab (also known as OPDIVO®), before and after the kidney cancer surgery to using the usual approach of surgically removing the kidney cancer followed by standard post-operative follow-up and monitoring. Nivolumab is a drug that may help stimulate your immune system to attack any cancer cells that may remain after surgery. The addition of nivolumab to the usual surgery could prevent your cancer from returning but it could also cause side effects. This research study will allow researchers to find out whether this different treatment is better, the same, or worse than the usual treatment for kidney cancer that has been removed but is at risk for coming back The study drug, nivolumab, is already FDA-approved for patients who have kidney cancer that has spread outside of the kidney to other organs or lymph nodes. The use of nivolumab in this study is investigational (not approved by the FDA) for your early stage of cancer where we do not know for sure if the disease has spread outside of the kidney. This research study will allow the researchers to know whether this different approach is better, the same, or worse than the usual approach. To be better, the study drug should improve how long you are able to live without any signs or symptoms of your cancer compared to the usual approach

    TRIAL NUMBER: LungMAP

    Title: LungMAP: A MASTER PROTOCOL TO EVALUATE BIOMARKER-DRIVEN THERAPIES AND IMMUNOTHERAPIES IN PREVIOUSLY-TREATED NON-SMALL CELL LUNG CANCER (Lung-MAP Screening Study)

    Purpose: 1.1 Primary Objective of the Master Protocol (LungMAP) The primary objective of this screening study is to test patient specimens to determine eligibility for participation in the biomarker-driven and non-matched sub-studies included within the Lung-MAP umbrella protocol. 1.2 Secondary Objectives a. Screening Success Rate Objective To evaluate the screen success rate defined as the percentage of screened patients that register for a therapeutic sub-study. Screen success rates will be evaluated for the total screened population and by the subset of patients screened following progression on previous therapy or pre-screened on current therapy. b. Translational Medicine Objectives 1. To evaluate circulating tumor DNA (ctDNA) and compare to the FMI Foundation tissue molecular profiling results in patients who submit a new biopsy for screening. 2. To establish a tissue/blood repository

    TRIAL NUMBER: NRG-LU002

    Title: MAINTENANCE SYSTEMIC THERAPY VERSUS CONSOLIDATIVE STEREOTACTIC BODY RADIATION THERAPY (SBRT) PLUS MAINTENANCE SYSTEMIC THERAPY FOR LIMITED METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC): A RANDOMIZED PHASE II/III TRIAL

    Purpose: (Arm 1): Maintenance systemic therapy should begin within 2 weeks of randomization. (Arm 2): Radiation should begin within 2 weeks of randomization, and maintenance systemic therapy should begin within 2 weeks of the completion of radiation.

    TRIAL NUMBER: EA6134

    Title: A Randomized Phase III Trial of Dabrafenib + Trametinib Followed by Ipilimumab + Nivolumab at Progression vs. Ipilimumab + Nivolumab Followed by Dabrafenib + Trametinib at Progression in Patients With Advanced BRAFV600 Mutant Melanoma

    Purpose: This randomized phase III trial studies how well initial treatment with ipilimumab and nivolumab followed by dabrafenib and trametinib works and compares it to initial treatment with dabrafenib and trametinib followed by ipilimumab and nivolumab in treating patients with stage III-IV melanoma that contains a mutation known as v-raf murine sarcoma viral oncogene homolog B V600 (BRAFV600) and cannot be removed by surgery. Ipilimumab and nivolumab may block tumor growth by targeting certain cells. Dabrafenib and trametinib may block tumor growth by targeting the BRAFV600 gene. It is not yet known whether treating patients with ipilimumab and nivolumab followed by dabrafenib and trametinib is more effective than treatment with dabrafenib and trametinib followed by ipilimumab and nivolumab.

    TRIAL NUMBER: S1801

    Title: A PHASE II RANDOMIZED STUDY OF ADJUVANT VERSUS NEOADJUVANT MK-3475 (PEMBROLIZUMAB) FOR CLINICALLY DETECTABLE STAGE III-IV HIGH RISK MELANOMA

    Purpose: Primary Outcome Measures : Event-free survival (EFS) in patients with high-risk resectable melanoma randomized to neoadjuvant pembrolizumab with patients randomized to adjuvant pembrolizumab [ Time Frame: Date of randomization to date of first progression or death assessed up to 10 years ] We will use exponential-mixture cure models to describe EFS patterns in the arms.

    Secondary Outcome Measures : Overall survival (OS) [ Time Frame: Up to 10 years ] Will be estimated using the Kaplan-Meier method and compared between arms using log-rank tests and Cox regression models.
    Disease control [ Time Frame: At 24 weeks ] Will be estimated using the Kaplan-Meier method and compared between arms using log-rank tests and Cox regression models.
    Local/regional control in the surgical site(s) [ Time Frame: Up to 10 years ] Will be estimated using the Kaplan-Meier method and compared between arms using log-rank tests and Cox regression models.
    Total number of pembrolizumab doses [ Time Frame: Up to 10 years ] Will use Fisher's exact test to compare the number of pembrolizumab doses received by patients on each treatment arm.
    Pathologic response rate [ Time Frame: Up to 10 years ] Will be tabulated for the neoadjuvant arm and exact 95% confidence intervals will be constructed.
    Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 response rate [ Time Frame: Up to 10 years ] Will be tabulated for the neoadjuvant arm and exact 95% confidence intervals will be constructed.
    Immune-related (i)RECIST response rate [ Time Frame: Up to 10 years ] Will be tabulated for the neoadjuvant arm and exact 95% confidence intervals will be constructed.

    TRIAL NUMBER: EAY131

    Title: EAY131: Molecular Analysis for Therapy Choice (NCI-MATCH)

    Purpose: This phase II trial studies how well treatment that is directed by genetic testing works in patients with solid tumors or lymphomas that have progressed following at least one line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment which targets their tumor's particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors or lymphomas.

    TRIAL NUMBER: EAZ171

    Title: Prospective Validation Trial of Taxane Therapy (Docetaxel or Weekly Paclitaxel) and Risk of Chemotherapy-Induced Peripheral Neuropathy in African American Women

    Purpose:

    Primary Outcome Measures :
    1. Validation of a prior germline predictor of paclitaxel-induced peripheral neuropathy (Arm A) [ Time Frame: Baseline ]
      Patients will be coded as having the event as long as grade 2-4 neuropathy based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 occurred at any time during the observation period. Patients without neuropathy or with maximum of grade 1 neuropathy during the whole observation period will be coded as having no event.


    Secondary Outcome Measures :
    1. Grade 2-4 taxane-induced peripheral neuropathy (TIPN) [ Time Frame: Up to 3 years post-registration ]
      Will be based on CTCAE between both Arm A versus (vs.) Arm.

    2. Patient-related outcome (PRO)-based neurotoxicity [ Time Frame: Up to 3 years post-registration ]
      Will be assessed using the Functional Assessment of Cancer Therapy (FACT)/Gynecologic Oncology Group (GOG)-Neurotoxicity (NTX) questionnaire. The FACT/GOG-Ntx neurotoxicity total score will be analyzed as a continuous variable. Linear mixed effect models with random intercept (repeated measures within single patients with unstructured covariance matrices) will be fit to estimate the average difference in FACT/GOG-Ntx neurotoxicity total score between high versus (vs.) low risk genotype groups in the paclitaxel arm. Time and patient and disease characteristics will be included as covariates in the linear mixed effect model. Genotype group-by-time interaction will be tested to see whether the difference between the two genotype groups depends on time. For comparison between arm A and arm B, the FACT/GOG-Ntx neurotoxicity total score change between the baseline and at end of treatment will be compared using two sample t test.

    3. Health-related quality of life (HRQoL) between both arms [ Time Frame: Up to 3 years post-registration ]
      The HRQoL total score will be analyzed as a continuous variable and compared between low and high-risk genotypes groups of the paclitaxel arm, and between the paclitaxel arm and the docetaxel arm groups, using two-sample t tests. Multivariable linear mixed effect models will also be fit to evaluate the time trend of HRQoL and to estimate the average group difference in HRQoL after adjusting for other covariates. Group-by-time interaction will be tested to see whether the difference in HRQoL between groups depends on time.

    4. Physical function between both arms [ Time Frame: Up to 3 years post-registration ]
      Will be measured using the (PROMIS) Physical Function version (v)2.0 Short From 10a. The PROMIS Physical Function T score will be analyzed as a continuous variable, and it will be compared between the two treatment arms (A&B) and for the high risk vs. low risk genotypes (in arm A) using two-sample t tests

    5. Financial toxicity between both arms [ Time Frame: Up to 6 months post-registration ]
      Will be assessed using the Comprehensive Score for Financial Toxicity (COST) scores and compared using a two-sample t tests.

    6. PRO-CTCAE scores of numbness, tingling, and general pain between both arms [ Time Frame: Up to 3 years post-registration ]
      Will present PRO-CTCAE scores for each attribute (frequency, severity and/or interference) separately and compare PRO-CTCAE severity (coded 0-4) with CTCAE grades for the corresponding time period.


    Other Outcome Measures:
    1. Association between Social economic determinants of health and treatment completion [ Time Frame: Baseline ]
      Social determinants of health (zip code, marital status, education, income & insurance status) will be associated with treatment completion per protocol

    2. Social economic determinants of health and FACT-Ntx neurotoxicity scores [ Time Frame: Baseline ]
      Social determinants of health (zip code, marital status, education, income & insurance status) will be associated with FACT-Ntx neurotoxicity scores

    3. Association between social determinants of health and FACT-Ntx HRQoL scores [ Time Frame: Baseline ]
      Social determinants of health (zip code, marital status, education, income & insurance status) will be associated with FACT-Ntx HRQoL scores

    TRIAL NUMBER: A221602

    Title: OLANZAPINEWITH ORWITHOUT FOSAPREPITANT FOR THE PREVENTION OF CHEMOTHERAPY INDUCED NAUSEA AND VOMITING (CINV) IN PATIENTS RECEIVING HIGHLY EMETOGENIC CHEMOTHERAPY (HEC): A PHASE III RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

    Purpose: Primary Outcome Measures : No nausea rate defined as a response of 0 in the nausea item of Nausea and Vomiting Daily Diary/Questionnaire in the overall (0-120 hours), acute (0-24 hours), and delayed (24-120 hours) periods [ Time Frame: Up to 120 hours ] The specific measure will be based on the proportion of patients with a value of 0, as measured by the single nausea item (scale 0-10, 0 is no symptoms, 10 is worst symptoms) of the Questionnaire. A modified intent-to-treat principle will be applied for statistical analysis of efficacy in evaluable patients. The proportions of patients with no nausea during the overall, the acute, and the delayed period will be summarized by treatment arm. They will be tested in a sequential manner, using a Simes gatekeeping procedure to maintain the overall significance level at the specified by the Lan-DeMets family of alpha spending function. The difference in no nausea proportions between arms will be estimated along with a one-sided 95% confidence interval. The tests and the confidence intervals will be constructed using normal approximation of the binomial distribution adjusted for the non-inferiority margin.

    Secondary Outcome Measures : Complete response (CR) (no emetic episodes and no use of rescue medication) during the acute, delayed and the overall periods as measured by the Nausea and Vomiting Daily Diary/Questionnaire [ Time Frame: Up to 120 hours ] The specific measure will be based on the proportion of patients who answered "None" to both questions concerning Vomiting episode(None, Once, Twice, More than twice) and number of extra nausea/vomiting pills taken (None, One, Two, More than two) in the Nausea and Vomiting Daily Diary/Questionnaire. The CR rate for the overall, the acute, and the delayed period will be summarized by treatment arm and will be compared using a Chi-squared test. The difference in CR rates between arms will be estimated along with a 95% confidence interval.
    Potential toxicities as ascribed to olanzapine as measured by the Nausea and Vomiting Daily Diary/Questionnaire [ Time Frame: Up to 1 year ] Potential toxicities includes nausea, undesired sedation, and undesired appetite, measured by three individual items ( nausea, undesired sedation, undesired appetite) of the Nausea and Vomiting Daily Dairy/Questionnaire(scale 0-10, 0 is no symptoms, 10 is worst symptoms). Incidences of toxicities will be summarized by type and by treatment arm. Incidences of toxicities will be compared between arms using a Chi-squared test or the Fisher's exact test as appropriate. In addition, undesired sedation and appetite increase as collected in the Nausea and Vomiting Daily Diary/Questionnaire will be analyzed by repeated measures analyses including descriptive statistics, graphical approaches, and growth curve models to account for the factor of day and time trend.
    Nausea scores (0-10) repeatedly measured by the Nausea and Vomiting Daily Diary/Questionnaire [ Time Frame: Up to 1 year ] The specific measure will be based on the by the single nausea item (scale 0-10, 0 is no symptoms, 10 is worst symptoms) of the Nausea and Vomiting Daily Diary/Questionnaire. Nausea scores (0-10) repeatedly measured by the Nausea and Vomiting Daily Diary/Questionnaire will be analyzed using the repeated measures analyses and growth curve models as described above for undesired sedation and increase in appetite.
    Frequency of rescue medication as measured by the Nausea and Vomiting Daily Diary/Questionnaire [ Time Frame: Up to 1 year ] The specific measure will be based on the single item : number of extra nausea/vomiting pills taken (None, One , Twice, More than twice) of the Nausea and Vomiting Daily Diary/Questionnaire. The proportion of patients taking any rescue medication as reported in the Nausea and Vomiting Daily Diary/Questionnaire will be summarized by treatment arm and will be compared between arms using a Chi-squared test or the Fisher's exact test as appropriate. In addition, the number of pills taken will be analyzed using the repeated measures analyses and growth curve models.

    TRIAL NUMBER: A031501

    Title: PHASE III RANDOMIZED ADJUVANT STUDY OF MK-3475 (PEMBROLIZUMAB) IN MUSCLE INVASIVE AND LOCALLY ADVANCED UROTHELIAL CARCINOMA (AMBASSADOR) VERSUS OBSERVATION

    Purpose: Primary Outcome Measures: Disease-free survival [ Time Frame: From randomization to the first metastatic recurrence (presence of any recurrent disease), or death, whichever occurs first, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.
    Overall survival [ Time Frame: From randomization to the date of death from any cause, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.

    Secondary Outcome Measures: Disease-free survival in PD-L1 positive and negative patients [ Time Frame: From randomization to the first metastatic recurrence (presence of any recurrent disease), or death, whichever occurs first, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.
    Overall survival in PD-L1 positive and negative patients [ Time Frame: From randomization to the date of death from any cause, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.

    Estimated Enrollment: 739 Actual Study Start Date: September 21, 2017 Estimated Study Completion Date: February 28, 2019 Estimated Primary Completion Date: February 28, 2019 (Final data collection date for primary outcome measure)

    • CHRISTUS Highland Medical Center
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    TRIAL NUMBER: A011401

    Title: A011401: Study Title for Study Participants: Breast Cancer WEight Loss Study (BWEL Study) Official Study Title for Internet Search on http://www.ClinicalTrials.gov: Randomized Phase III Trial Evaluating the Role of Weight Loss in Adjuvant Treatment of Overweight and Obese Women with Early Breast Cancer

    Purpose: This study is being done to see if losing weight may help prevent breast cancer from coming back (recurring). Previous studies have found that women who are overweight or obese when their breast cancer is found (diagnosed) have a greater risk of their breast cancer recurring, as compared to women who were thinner when their cancer was diagnosed. At this time we do not know whether or not losing weight will reduce the risk of breast cancer returning. This study seeks to determine whether or not the higher risk for breast cancer recurrence in women who are overweight or obese when they are diagnosed with breast cancer could be reduced or eliminated if weight is lost. It is important to note that we do not know how much weight would need to be lost to lower the risk of breast cancer recurrence, or whether this strategy would work for all women. This study will help to show us whether weight loss programs should be a part of breast cancer treatment.

    TRIAL NUMBER: EA1131

    Title: A Randomized Phase III Post-Operative Trial of Platinum Based Chemotherapy Vs. Observation in Patients with Residual Triple-Negative Basal-Like Breast Cancer following Neoadjuvant Chemotherapy

    Purpose: The purpose of this study is to compare the IDFS in TNBC patients with residual basal-like disease after neoadjuvant chemotherapy who are randomized to post-preoperative platinum based chemotherapy with those who are randomized to observation. At present, upon completion of neoadjuvant therapy, the standard of care for patients with TNBC (who have no clinical evidence of metastatic disease after surgical excision of the cancer regardless of burden of residual disease) is observation, since there is no additional therapies available with proven impact. This study could provide a possible alternative treatment, which makes it appropriate for the population.

    TRIAL NUMBER: NRG-BR003

    Title: A Randomized Phase III Trial of Adjuvant Therapy Comparing Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel With or Without Carboplatin for Node-Positive or High-Risk Node-Negative Triple-Negative Invasive Breast Cancer

    Purpose: This randomized phase III trial studies how well doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel with or without carboplatin work in treating patients with triple-negative breast cancer. Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether doxorubicin hydrochloride and cyclophosphamide is more effective when followed by paclitaxel alone or paclitaxel and carboplatin in treating triple-negative breast cancer.

    TRIAL NUMBER: WF 97116

    Title: Phase 3 Randomized Placebo Controlled Clinical Trial of Donepezil - WF 97116

    Purpose: This study is to compare the safety and effects of donepezil (Aricept) or if it decreases memory loss after receiving chemotherapy for breast cancer.

    TRIAL NUMBER: A151216

    Title: Genetic Testing For Patients with Resectable or Resected Lung Cancer: Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST)

    Purpose: PRIMARY OBJECTIVES:
    I. To centrally genotype resected lung adenocarcinomas for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements to facilitate accrual to randomized adjuvant studies.
    II. To obtain clinically annotated tumor tissue and patient-matched non-malignant deoxyribonucleic acid (DNA) from peripheral blood, as well as detailed epidemiologic and clinical follow-up data, to allow clinically annotated advanced genomic analyses in concert with the National Cancer Institute (NCI) Center for Cancer Genomics (CCG).
    SECONDARY OBJECTIVES:
    I. To characterize the natural history of EGFR and ALK wild-type lung cancers to allow subsequent development of targeted therapies against genotype-defined sub-populations in the adjuvant and recurrent settings.
    II. To cross-validate local genotyping assays for EGFR and ALK with a central reference standard.
    TERTIARY OBJECTIVES:
    I. To study the genomic evolution of lung cancers by comparing genomic characteristics at resection and at recurrence.
    OUTLINE:
    Patients undergo collection of blood and tissue samples for EGFR and ALK testing via direct sequencing and fluorescence in situ hybridization (FISH). Patients that have had surgery prior to pre-registration will submit samples from the previous surgery for testing.
    After completion of study, patients that are not enrolled on either A081105 or E4512 are followed up every 6 months for 5 years.

    TRIAL NUMBER: E4512

    Title: A Phase III Double-Blind Trial for Surgically Resected Early Stage Non-Small Cell Lung Cancer: Crizotinib versus Placebo for Patients with Tumors Harboring the Anaplastic Lymphoma Kinase (ALK) Fusion Protein

    Purpose: PRIMARY OBJECTIVES:
    I. To evaluate whether adjuvant therapy with crizotinib will result in improved overall survival (OS) over placebo for patients with stage IB >= 4 cm, II and IIIA, anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) following surgical resection.
    SECONDARY OBJECTIVES:
    I. To evaluate and compare disease-free survival (DFS) associated with crizotinib and placebo.
    II. To evaluate the safety profile of crizotinib when given in the adjuvant therapy setting.
    III. To collect tumor tissue and blood specimens for future research.
    OUTLINE: Patients are randomized to 1 of 2 treatment arms.
    ARM A: Patients receive crizotinib orally (PO) twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
    ARM B: Patients receive placebo PO BID on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
    After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly for 5 years.

    TRIAL NUMBER: A031501

    Title: PHASE III RANDOMIZED ADJUVANT STUDY OF MK-3475 (PEMBROLIZUMAB) IN MUSCLE INVASIVE AND LOCALLY ADVANCED UROTHELIAL CARCINOMA (AMBASSADOR) VERSUS OBSERVATION

    Purpose: Primary Outcome Measures: Disease-free survival [ Time Frame: From randomization to the first metastatic recurrence (presence of any recurrent disease), or death, whichever occurs first, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.
    Overall survival [ Time Frame: From randomization to the date of death from any cause, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.

    Secondary Outcome Measures: Disease-free survival in PD-L1 positive and negative patients [ Time Frame: From randomization to the first metastatic recurrence (presence of any recurrent disease), or death, whichever occurs first, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.
    Overall survival in PD-L1 positive and negative patients [ Time Frame: From randomization to the date of death from any cause, assessed up to 5 years ] The stratified proportional hazards model will be the primary analysis. The hazard ratio and its 95% confidence interval from the stratified Cox model with a single treatment covariate will be reported. The unstratified hazard ratio will also be presented.

    Estimated Enrollment: 739 Actual Study Start Date: September 21, 2017 Estimated Study Completion Date: February 28, 2019 Estimated Primary Completion Date: February 28, 2019 (Final data collection date for primary outcome measure)

    • Ochsner Medical Center Kenner
    • 16 Trials Available
    • CONTACT US

    TRIAL NUMBER: A011401

    Title: A011401: Study Title for Study Participants: Breast Cancer WEight Loss Study (BWEL Study) Official Study Title for Internet Search on http://www.ClinicalTrials.gov: Randomized Phase III Trial Evaluating the Role of Weight Loss in Adjuvant Treatment of Overweight and Obese Women with Early Breast Cancer

    Purpose: This study is being done to see if losing weight may help prevent breast cancer from coming back (recurring). Previous studies have found that women who are overweight or obese when their breast cancer is found (diagnosed) have a greater risk of their breast cancer recurring, as compared to women who were thinner when their cancer was diagnosed. At this time we do not know whether or not losing weight will reduce the risk of breast cancer returning. This study seeks to determine whether or not the higher risk for breast cancer recurrence in women who are overweight or obese when they are diagnosed with breast cancer could be reduced or eliminated if weight is lost. It is important to note that we do not know how much weight would need to be lost to lower the risk of breast cancer recurrence, or whether this strategy would work for all women. This study will help to show us whether weight loss programs should be a part of breast cancer treatment.

    TRIAL NUMBER: EA1131

    Title: A Randomized Phase III Post-Operative Trial of Platinum Based Chemotherapy Vs. Observation in Patients with Residual Triple-Negative Basal-Like Breast Cancer following Neoadjuvant Chemotherapy

    Purpose: The purpose of this study is to compare the IDFS in TNBC patients with residual basal-like disease after neoadjuvant chemotherapy who are randomized to post-preoperative platinum based chemotherapy with those who are randomized to observation. At present, upon completion of neoadjuvant therapy, the standard of care for patients with TNBC (who have no clinical evidence of metastatic disease after surgical excision of the cancer regardless of burden of residual disease) is observation, since there is no additional therapies available with proven impact. This study could provide a possible alternative treatment, which makes it appropriate for the population.

    TRIAL NUMBER: NRG-BR003

    Title: A Randomized Phase III Trial of Adjuvant Therapy Comparing Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel With or Without Carboplatin for Node-Positive or High-Risk Node-Negative Triple-Negative Invasive Breast Cancer

    Purpose: This randomized phase III trial studies how well doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel with or without carboplatin work in treating patients with triple-negative breast cancer. Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether doxorubicin hydrochloride and cyclophosphamide is more effective when followed by paclitaxel alone or paclitaxel and carboplatin in treating triple-negative breast cancer.

    TRIAL NUMBER: NSABP B-51

    Title: A Randomized Phase III Clinical Trial Evaluating Post-Mastectomy Chestwall and Regional Nodal XRT and Post-Lumpectomy Regional Nodal XRT in Patients With Positive Axillary Nodes Before Neoadjuvant Chemotherapy Who Convert to Pathologically Negative Axillary Nodes After Neoadjuvant Chemotherapy

    Purpose: This randomized phase III trial studies standard or comprehensive radiation therapy in treating patients with early-stage breast cancer who have undergone surgery. Radiation therapy uses high-energy x rays to kill tumor cells. It is not yet known whether comprehensive radiation therapy is more effective than standard radiation therapy in treating patients with breast cancer

    TRIAL NUMBER: S1418

    Title: A Randomized, Phase III Trial to Evaluate the Efficacy and Safety of MK-3475 (Pembrolizumab) as Adjuvant Therapy for Triple Receptor-Negative Breast Cancer With ? 1 cm Residual Invasive Cancer or Positive Lymph Nodes (ypN+) After Neoadjuvant Chemotherapy

    Purpose: This randomized phase III trial studies how well pembrolizumab works in treating triple-negative breast cancer. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

    TRIAL NUMBER: DCP-001

    Title: DCP-001, Use of a Clinical Trial Screening Tool to Address Cancer Health Disparities in the NCI Community Oncology Research Program (NCORP)

    Purpose: The protocol is not a scientific study; rather, a method to implement the screening tool and allow the collection and analyses of expanded data with informed consent. Investigators also enroll patients into NCI-treatment trials. The tool, based on a screening log successfully used within the NCI Community Cancer Centers Program (NCCCP), has been streamlined and integrated into the sites’ workflow by using OPEN. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. Also missing from the existing data is the context of care, within the communities themselves where most cancer and at risk of cancer patients receive care which is the focus of NCORP. The profile of patients accrued to NCI-sponsored clinical trials lacks both racial/ethnic and socioeconomic diversity. Accrued patients tend to be insured, highly educated and of higher socioeconomic means. The NCI Community Oncology Research Program (NCORP), a network of diverse community oncology practices, provides an opportunity to collect this important but missing clinical trials screening and expanded demographics in order to better understand the complex and multi-factorial influences affecting clinical trial participation. NCORP's clinical trials portfolio includes cancer control, prevention, screening, symptom science, and cancer care delivery research.

    TRIAL NUMBER: A021502

    Title: Randomized Trial of Standard Chemotherapy Alone or Combined With Atezolizumab as Adjuvant Therapy for Patients With Stage III Colon Cancer and Deficient DNA Mismatch Repair

    Purpose: This randomized phase III trial studies combination chemotherapy and atezolizumab to see how well it works compared with combination chemotherapy alone in treating patients with stage III colon cancer and deficient deoxyribonucleic acid (DNA) mismatch repair. Drugs used in combination chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as atezolizumab, may interfere with the ability of tumor cells to grow and spread. Giving combination chemotherapy with atezolizumab may work better than combination chemotherapy alone in treating patients with colon cancer.

    TRIAL NUMBER: EA2174

    Title: A PHASE II/III STUDY OF PERI-OPERATIVE NIVOLUMAB AND IPILIMUMAB IN PATIENTS WITH LOCOREGIONAL ESOPHAGEAL AND GASTROESOPHAGEAL JUNCTION ADENOCARCINOMA

    Purpose: Primary Outcome Measures : Pathologic complete response (Step I) [ Time Frame: Up to 5 weeks ] The study with compare the pathologic complete response of Arm A and Arm B using a one-sided 0.10 level chi-squared test for proportions.
    Disease-free survival (DFS) (Step 2) [ Time Frame: From the adjuvant treatment randomization assessed for up to 7 years ] DFS measured from the adjuvant treatment randomization will be the endpoint of the adjuvant portion of the study and to achieve the desired power it is expected that patients will be followed for an additional year post completion of accrual to the adjuvant portion. The DFS comparison will be between patients randomized to Arm C (nivolumab) versus Arm D (nivolumab plus ipilimumab) using a one-sided 0.10 level stratified log rank test.

    Secondary Outcome Measures : Incidence of adverse events [ Time Frame: Up to 7 years ] Graded according to Common Terminology Criteria for Adverse Events version 5.0. Toxicity will be evaluated among all treated patients regardless of eligibility and interim analyses of toxicity are performed twice yearly. The study will have sufficient precision to provide 95% confidence intervals on toxicity
    Overall survival [ Time Frame: From the time of first randomization up to 7 years ] Analyses will be descriptive in nature and will not follow any formal interim monitoring.
    DFS [ Time Frame: From the time of first randomization up to 7 years ] The DFS comparison will be between patients randomized to Arm C (nivolumab) versus Arm D (nivolumab plus ipilimumab) using a one-sided 0.10 level stratified log rank test.

    Other Outcome Measures: Percent change in mean volumetric apparent diffusion coefficient (ADC) [ Time Frame: Baseline to mid-treatment ] The study will assess the area under the receiver operating characteristic curve of the changes of apparent diffusion coefficient (ADC) value.

    TRIAL NUMBER: S0820

    Title: A DOUBLE BLIND PLACEBO-CONTROLLED TRIAL OF EFLORNITHINE AND SULINDAC TO PREVENT RECURRENCE OF HIGH RISK ADENOMAS AND SECOND PRIMARY COLORECTAL CANCERS IN PATIENTS WITH STAGE 0-III COLON CANCER, PHASE III

    Purpose: The purpose of this study is to assess whether eflornithine 500 mg or sulindac 150 mg are effective in reducing the 3-year event rate of high risk adenoma or second primary colorectal cancer in Stage 0, I II and III colon cancer patients. The primary hypothesis will test the main effect of each agent, as well as the comparison of placebo alone to the combination of sulindac and eflornithine.

    TRIAL NUMBER: EA2142

    Title: Randomized Phase II Study of Cisplatin and Etoposide Versus Temozolomide and Capecitabine in Patients With Advanced G3 Non-small Cell Gastroenteropancreatic Neuroendocrine Carcinomas

    Purpose: This randomized phase II trial studies how well temozolomide and capecitabine work compared to standard treatment with cisplatin and etoposide in treating patients with neuroendocrine carcinoma of the gastrointestinal tract or pancreas that has spread to other parts of the body (metastatic) or cannot be removed by surgery. Drugs used in chemotherapy, such as temozolomide, capecitabine, cisplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Certain types of neuroendocrine carcinomas may respond better to treatments other than the current standard treatment of cisplatin and etoposide. It is not yet known whether temozolomide and capecitabine may work better than cisplatin and etoposide in treating patients with this type of neuroendocrine carcinoma, called non-small cell neuroendocrine carcinoma.

    TRIAL NUMBER: A151216

    Title: Genetic Testing For Patients with Resectable or Resected Lung Cancer: Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST)

    Purpose: PRIMARY OBJECTIVES:
    I. To centrally genotype resected lung adenocarcinomas for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements to facilitate accrual to randomized adjuvant studies.
    II. To obtain clinically annotated tumor tissue and patient-matched non-malignant deoxyribonucleic acid (DNA) from peripheral blood, as well as detailed epidemiologic and clinical follow-up data, to allow clinically annotated advanced genomic analyses in concert with the National Cancer Institute (NCI) Center for Cancer Genomics (CCG).
    SECONDARY OBJECTIVES:
    I. To characterize the natural history of EGFR and ALK wild-type lung cancers to allow subsequent development of targeted therapies against genotype-defined sub-populations in the adjuvant and recurrent settings.
    II. To cross-validate local genotyping assays for EGFR and ALK with a central reference standard.
    TERTIARY OBJECTIVES:
    I. To study the genomic evolution of lung cancers by comparing genomic characteristics at resection and at recurrence.
    OUTLINE:
    Patients undergo collection of blood and tissue samples for EGFR and ALK testing via direct sequencing and fluorescence in situ hybridization (FISH). Patients that have had surgery prior to pre-registration will submit samples from the previous surgery for testing.
    After completion of study, patients that are not enrolled on either A081105 or E4512 are followed up every 6 months for 5 years.

    TRIAL NUMBER: E4512

    Title: A Phase III Double-Blind Trial for Surgically Resected Early Stage Non-Small Cell Lung Cancer: Crizotinib versus Placebo for Patients with Tumors Harboring the Anaplastic Lymphoma Kinase (ALK) Fusion Protein

    Purpose: PRIMARY OBJECTIVES:
    I. To evaluate whether adjuvant therapy with crizotinib will result in improved overall survival (OS) over placebo for patients with stage IB >= 4 cm, II and IIIA, anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) following surgical resection.
    SECONDARY OBJECTIVES:
    I. To evaluate and compare disease-free survival (DFS) associated with crizotinib and placebo.
    II. To evaluate the safety profile of crizotinib when given in the adjuvant therapy setting.
    III. To collect tumor tissue and blood specimens for future research.
    OUTLINE: Patients are randomized to 1 of 2 treatment arms.
    ARM A: Patients receive crizotinib orally (PO) twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
    ARM B: Patients receive placebo PO BID on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
    After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly for 5 years.

    TRIAL NUMBER: EA6134

    Title: A Randomized Phase III Trial of Dabrafenib + Trametinib Followed by Ipilimumab + Nivolumab at Progression vs. Ipilimumab + Nivolumab Followed by Dabrafenib + Trametinib at Progression in Patients With Advanced BRAFV600 Mutant Melanoma

    Purpose: This randomized phase III trial studies how well initial treatment with ipilimumab and nivolumab followed by dabrafenib and trametinib works and compares it to initial treatment with dabrafenib and trametinib followed by ipilimumab and nivolumab in treating patients with stage III-IV melanoma that contains a mutation known as v-raf murine sarcoma viral oncogene homolog B V600 (BRAFV600) and cannot be removed by surgery. Ipilimumab and nivolumab may block tumor growth by targeting certain cells. Dabrafenib and trametinib may block tumor growth by targeting the BRAFV600 gene. It is not yet known whether treating patients with ipilimumab and nivolumab followed by dabrafenib and trametinib is more effective than treatment with dabrafenib and trametinib followed by ipilimumab and nivolumab.

    TRIAL NUMBER: EAY131

    Title: EAY131: Molecular Analysis for Therapy Choice (NCI-MATCH)

    Purpose: This phase II trial studies how well treatment that is directed by genetic testing works in patients with solid tumors or lymphomas that have progressed following at least one line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment which targets their tumor's particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors or lymphomas.

    TRIAL NUMBER: S1609

    Title: SWOG 1609: DART: Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors Treatment with Ipilimumab and Nivolumab for Rare Cancers

    Purpose: Both Ipilimumab and Nivolumab have already been FDA-approved to treat other cancers. However, Ipilimumab and Nivolumab are investigational and not FDA-approved for use in combination in treating rare cancers or cancers of unknown primary origin.

    TRIAL NUMBER: A191402CD

    Title: Decision Aids in Improving Knowledge in Patients With Newly Diagnosed Prostate Cancer

    Purpose: This randomized phase III trial studies how well decision aids work in improving knowledge in patients with newly diagnosed prostate cancer. Decision aids may improve patients' knowledge of their condition and options for treatment, and may also help when talking with their doctor.

    • LSU HSC - Shreveport University Health - FWCC
    • Caddo
    • 15 Trials Available
    • CONTACT US

    TRIAL NUMBER: A011401

    Title: A011401: Study Title for Study Participants: Breast Cancer WEight Loss Study (BWEL Study) Official Study Title for Internet Search on http://www.ClinicalTrials.gov: Randomized Phase III Trial Evaluating the Role of Weight Loss in Adjuvant Treatment of Overweight and Obese Women with Early Breast Cancer

    Purpose: This study is being done to see if losing weight may help prevent breast cancer from coming back (recurring). Previous studies have found that women who are overweight or obese when their breast cancer is found (diagnosed) have a greater risk of their breast cancer recurring, as compared to women who were thinner when their cancer was diagnosed. At this time we do not know whether or not losing weight will reduce the risk of breast cancer returning. This study seeks to determine whether or not the higher risk for breast cancer recurrence in women who are overweight or obese when they are diagnosed with breast cancer could be reduced or eliminated if weight is lost. It is important to note that we do not know how much weight would need to be lost to lower the risk of breast cancer recurrence, or whether this strategy would work for all women. This study will help to show us whether weight loss programs should be a part of breast cancer treatment.

    TRIAL NUMBER: A211601

    Title: EVALUATION OF MAMMOGRAPHIC BREAST DENSITY EFFECT OF ASPIRIN: A COMPANION STUDY TO ALLIANCE STUDY A011502

    Purpose: Primary Outcome Measures : Mammographic percent density (MPD) in the contralateral (unaffected) breast between the aspirin and placebo arms [ Time Frame: At 1 year post-registration to A011502 ] The 1-year mammographic percent density (MPD) in the contralateral (unaffected) breast between the aspirin and placebo arms will be compared. Analysis of covariance (ANCOVA) adjusting for baseline MPD will be used to compare MPD at 1 year between the arms. After adjusting for the baseline MPD, it will be concluded that the 1-year MPD is statistically different between the two arms if the corresponding two-sided p-value is less than 0.05. If normality of the primary variable is questionable, then variable transformation or nonparametric Wilcoxon rank-sum test on simple change MPD values may be considered as alternative approaches. A subsequent exploratory analysis will include all patients with an MPD computed at baseline (regardless of that baseline value) and at 1-year post-baseline.

    Secondary Outcome Measures : Mammographic percent density (MPD) in the contralateral (unaffected) breast between the aspirin and placebo arms [ Time Frame: At 2 years post-registration to A011502 ] The 2-year mammographic breast density in the contralateral (unaffected) breast between the two arms for those patients with a baseline mammographic percent density (MPD) >= 25% and a 2-year post-baseline MPD will be compared. ANCOVA will be used to compare MPD between the arms. The corresponding test for the between-arm difference in MPD at 2-years will also be carried out at the 0.05 significance level.

    TRIAL NUMBER: NRG-BR003

    Title: A Randomized Phase III Trial of Adjuvant Therapy Comparing Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel With or Without Carboplatin for Node-Positive or High-Risk Node-Negative Triple-Negative Invasive Breast Cancer

    Purpose: This randomized phase III trial studies how well doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel with or without carboplatin work in trea