<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04484818</url>
  </required_header>
  <id_info>
    <org_study_id>EA8183</org_study_id>
    <secondary_id>NCI-2020-02383</secondary_id>
    <secondary_id>EA8183</secondary_id>
    <secondary_id>EA8183</secondary_id>
    <secondary_id>U10CA180820</secondary_id>
    <nct_id>NCT04484818</nct_id>
  </id_info>
  <brief_title>Testing the Addition of Darolutamide to Hormonal Therapy (Androgen Deprivation Therapy [ADT]) After Surgery for Men With High-Risk Prostate Cancer, The ERADICATE Study</brief_title>
  <official_title>A Phase III Double Blinded Study of Early Intervention After RADICAl ProstaTEctomy With Androgen Deprivation Therapy With or Without Darolutamide vs. Placebo in Men at Highest Risk of Prostate Cancer Metastasis by Genomic Stratification (ERADICATE)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ECOG-ACRIN Cancer Research Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Eastern Cooperative Oncology Group</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase III trial compares the effect of adding darolutamide to ADT versus ADT alone after&#xD;
      surgery for the treatment of high-risk prostate cancer. ADT reduces testosterone levels in&#xD;
      the blood. Testosterone is a hormone made mainly in the testes and is needed to develop and&#xD;
      maintain male sex characteristics, such as facial hair, deep voice, and muscle growth. It&#xD;
      also plays role in prostate cancer development. Darolutamide blocks the actions of the&#xD;
      androgens (e.g. testosterone) in the tumor cells and in the body. Giving darolutamide with&#xD;
      ADT may work better in eliminating or reducing the size of the cancer and/or prevent it from&#xD;
      returning compared to ADT alone in patients with prostate cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To determine whether 12 months of androgen deprivation therapy (ADT) and darolutamide&#xD;
      improves metastasis-free survival (MFS) compared to 12 months of ADT plus placebo in men with&#xD;
      high risk prostate cancer (defined by Cancer of the Prostate Risk Assessment Post-surgical&#xD;
      [CAPRA-S] score &gt;= 3 and a high Decipher score (&gt;= 0.6) [C3+D+]) who have undergone radical&#xD;
      prostatectomy.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To determine whether 12 months of ADT and darolutamide improves recurrence-free survival&#xD;
      (RFS) compared to 12 months of ADT plus placebo in men with high-risk prostate cancer that&#xD;
      have undergone radical prostatectomy.&#xD;
&#xD;
      II. To determine whether 12 months of ADT and darolutamide improves event-free survival (EFS)&#xD;
      compared to 12 months of ADT plus placebo in men with high-risk prostate cancer that have&#xD;
      undergone radical prostatectomy.&#xD;
&#xD;
      III. To determine whether 12 months of ADT and darolutamide improves overall survival (OS)&#xD;
      compared to 12 months of ADT plus placebo in men with high-risk prostate cancer that have&#xD;
      undergone radical prostatectomy.&#xD;
&#xD;
      IV. To determine the rate of testosterone recovery and time to testosterone recovery in each&#xD;
      treatment arm.&#xD;
&#xD;
      V. To evaluate the safety and tolerability of ADT and darolutamide.&#xD;
&#xD;
      CORRELATIVE OBJECTIVES FOR EXPLORATORY BIOMARKERS:&#xD;
&#xD;
      I. To discover a novel gene expression signature in the Decipher transcriptome platforms that&#xD;
      is predictive of clinical outcome, as defined by the primary and secondary objectives of this&#xD;
      study, in response to ADT by intensification with darolutamide versus ADT alone.&#xD;
&#xD;
      II. To assess the prevalence of subclasses of established transcriptome expression signatures&#xD;
      and prospectively validate their predictive value for ADT response, these include: (i)&#xD;
      androgen (AR) activity (ii) Basal-luminal subtyping based on modified PAM50, and (iii) ADT&#xD;
      score.&#xD;
&#xD;
      III. To assess whether the spectrum of high Decipher scores (0.6-1.0), prostate-specific&#xD;
      antigen (PSA) levels at presentation and post-radical prostatectomy (RP) and final pathology&#xD;
      variables affect the response and outcome to ADT and darolutamide.&#xD;
&#xD;
      QUALITY OF LIFE (QOL) OBJECTIVES:&#xD;
&#xD;
      I. To compare overall quality of life, measured by Functional Assessment of Cancer&#xD;
      Therapy-Prostate (FACT-P) total score, at 18 months between the two arms. (Primary) II. To&#xD;
      compare the change in overall quality of life, measured by FACT-P total score, from baseline&#xD;
      to 18 months between the two arms. (Secondary) III. To compare patient-reported fatigue&#xD;
      (Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue scores) at 12 months&#xD;
      between the two treatment arms. (Secondary) IV. To compare the change in subjective&#xD;
      patient-reported cognitive function (FACT-Cognitive [Cog]) from baseline to 12 months between&#xD;
      the treatment arms. (Exploratory) V. To compare subjective patient-reported cognitive&#xD;
      function (FACT-Cog scores) at 12 months between the two treatment arms. (Exploratory)&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 arms.&#xD;
&#xD;
      ARM I: Patients receive goserelin acetate, leuprolide acetate, or triptorelin via injection&#xD;
      every 3 months for 12 months (4 injections), every 4 months for 12 months (3 injections), or&#xD;
      every month for 12 months (12 injections) in the absence of disease progression or&#xD;
      unacceptable toxicity. Patients also receive a placebo four times daily (QID) for 52 weeks in&#xD;
      the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      ARM II: Patients receive goserelin acetate, leuprolide acetate, or triptorelin via injection&#xD;
      every 3 months for 12 months (4 injections), every 4 months for 12 months (3 injections), or&#xD;
      every month for 12 months (12 injections) in the absence of disease progression or&#xD;
      unacceptable toxicity. Patients also receive darolutamide QID for 52 weeks in the absence of&#xD;
      disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months for 36 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 1, 2021</start_date>
  <completion_date type="Anticipated">May 31, 2028</completion_date>
  <primary_completion_date type="Anticipated">May 31, 2028</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Metastasis-free survival (MFS)</measure>
    <time_frame>From randomization to development of metastatic disease or death, whichever occurs first, assessed up to 36 months</time_frame>
    <description>The primary comparison will be an intention-to-treat analysis of all randomized patients. The method of Kaplan and Meier will be used to characterize the time-to-event endpoints, and a logrank test will be used to compare these endpoints across treatments.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Recurrence-free survival (RFS)</measure>
    <time_frame>From randomization to any of the MFS events, pelvic lymph node recurrence or detectable prostate-specific antigen (PSA) (PSA &gt;= 0.2 ng/mL, confirmed by a second PSA of the same level or higher), whichever occurs first, assessed up to 36 months</time_frame>
    <description>The method of Kaplan and Meier will be used to characterize the time-to-event endpoints, and a logrank test will be used to compare these endpoints across treatments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-free survival</measure>
    <time_frame>From randomization to any of the RFS events, treatment with salvage radiation therapy with or without systemic therapy, or initiation of systemic therapy for presumed recurrence, whichever occurs first, assessed up to 36 months</time_frame>
    <description>The method of Kaplan and Meier will be used to characterize the time-to-event endpoints, and a logrank test will be used to compare these endpoints across treatments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From randomization to death by any cause or date last known alive, assessed up to 36 months</time_frame>
    <description>The method of Kaplan and Meier will be used to characterize the time-to-event endpoints, and a logrank test will be used to compare these endpoints across treatments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Testosterone recovery rate</measure>
    <time_frame>At time of disease progression, assessed up to 36 months</time_frame>
    <description>Exact binomial confidence intervals will be used to describe the proportions of patients with testosterone recovery in each arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to testosterone recovery</measure>
    <time_frame>From randomization to a return of serum testosterone level to greater than or equal to lower limit of normal for the testosterone assay, assessed up to 36 months</time_frame>
    <description>The method of Kaplan and Meier will be used to characterize the time-to-event endpoints, and a logrank test will be used to compare these endpoints across treatments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>Up to 78 weeks</time_frame>
    <description>Toxicity will be defined using the Common Terminology Criteria for Adverse Events version 5.0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in quality of life: Functional Assessment of Cancer Therapy (FACT)</measure>
    <time_frame>Baseline up to 18 months</time_frame>
    <description>Will be assessed by the Functional Assessment of Cancer Therapy (FACT) - Prostate, FACT - Cognitive, and Functional Assessment of Chronic Illness Therapy - Fatigue. Fatigue instruments at baseline, 6, 12 and 18 months, and descriptive statistics will be used to characterize quality of life over time in each arm. Each item is answered on a 5-point Likert-type scale, where a value of 0 indicates the statement is not applicable, and a value of 5 indicates the statement is applicable to the respondent. Subgroup analysis will be performed among patients who receive adjuvant radiation therapy and patients who do not receive adjuvant radiation therapy in each arm. Mixed effect models will be constructed as an exploratory analysis to estimate the time profile of quality of life assessments in the two arms and to evaluate treatment-by-time interactions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall quality of life: Functional Assessment of Cancer Therapy (FACT)</measure>
    <time_frame>At 18 months</time_frame>
    <description>Will be assessed by the Functional Assessment of Cancer Therapy (FACT) - Prostate total score. The total score can range from 0 to 156, where a higher value indicates a better quality of life. Mixed effect models will be constructed as an exploratory analysis to estimate the time profile of quality of life assessments in the two arms and to evaluate treatment-by-time interactions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Functional Assessment of Cancer Therapy (FACT) - Prostate score</measure>
    <time_frame>Baseline up to 18 months</time_frame>
    <description>A paired t test will be used to compare Functional Assessment of Cancer Therapy (FACT) - Prostate scores at these two time points in each arm. The total score can range from 0 to 156, where a higher value indicates a better quality of life. A two-sample t test will be performed to compare the changes in FACT - Prostate scores from baseline to 18 months between the two arms. Mixed effect models will be constructed as an exploratory analysis to estimate the time profile of quality of life assessments in the two arms and to evaluate treatment-by-time interactions.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Cognitive function</measure>
    <time_frame>At 12 months (completion of treatment)</time_frame>
    <description>Will be measured between the two arms by Functional Assessment of Cancer Therapy (FACT) - Cognitive. The FACT-Cognitive has four subscales: perceived cognitive impairments (PCI), perceived cognitive abilities, impact of perceived cognitive impairment on quality of life, and comments from others on cognitive function. Summary statistics will be used to describe each subscale at each time point and the PCI subscale score, which ranges from 0-72, where higher values indicate better quality of life, at 12 months will be the primary measurement of this analysis. Bonferroni correction will be employed for the 3 follow-up time points of interest (6, 12, and 18 months) to make the analysis conservative. Mixed effect models will be constructed as an exploratory analysis to estimate the time profile of quality of lifeassessments in the two arms and to evaluate treatment-by-time interactions.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in cognitive function</measure>
    <time_frame>Baseline up to 12 months (completion of treatment)</time_frame>
    <description>Will be measured between the two arms by Functional Assessment of Cancer Therapy (FACT) - Cognitive. The FACT-Cognitive has four subscales: perceived cognitive impairments (PCI), perceived cognitive abilities, impact of perceived cognitive impairment on quality of life, and comments from others on cognitive function. Summary statistics will be used to describe each subscale at each time point and the PCI subscale score, which ranges from 0-72, where higher values indicate better quality of life, at 12 months will be the primary measurement of this analysis. Bonferroni correction will be employed for the 3 follow-up time points of interest (6, 12, and 18 months) to make the analysis conservative. Mixed effect models will be constructed as an exploratory analysis to estimate the time profile of quality of life assessments in the two arms and to evaluate treatment-by-time interactions.</description>
  </other_outcome>
  <other_outcome>
    <measure>Identification of novel gene expression signatures</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>The associations between the gene expression signatures and clinical outcomes will be assessed by Cox proportional hazards models and logrank test.</description>
  </other_outcome>
  <other_outcome>
    <measure>Prognostic value of established signatures</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>Will include androgen receptor activity, basal-luminal subtyping by modified PAM50 and androgen deprivation therapy score using Cox proportional hazards models. Similar analysis will be performed to evaluate the prognostic value of luminal-basal subtype. The treatment-by-subtype interaction will also be assessed. For androgen deprivation therapy score, patients will be categorized into either low or high androgen deprivation therapy score using a cutoff of 0.36.</description>
  </other_outcome>
  <other_outcome>
    <measure>Decipher scores</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>Will be associated with MFS as well as disease characteristics. Cox proportional hazards models will be performed with adjustment for important disease characteristics, including prostate-specific antigen, Gleason score, disease stage, pathology of the radical prostatectomy specimen, etc. Decipher score could be categorized into a few risk groups and the Akaike information criterion method will be used to determine the optimal number of cutoff points. To assess whether treatment effect is affected by Decipher score levels, the treatment-by-Decipher interactions will be included in the model as well. Decipher scores range from 0.00 to 1.00, where higher values indicate higher risk disease.</description>
  </other_outcome>
  <other_outcome>
    <measure>Genome-wide alterations</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>Prostate cancer specimens will be banked for future studies to perform genome-wide alterations in coding and non-coding deoxyribonucleic acid sequences. To identify the genetic alterations that are associated with development of metastasis, Cox proportional hazards models and logrank test will be used. The analysis will focus on actionable alterations first. The treatment-by-alteration interactions will also be assessed to determine whether response to darolutamide is affected by distinct genomic subgroups. Ultimately the findings on gene expression signatures and deoxyribonucleic acid alterations will be assessed in the models simultaneously to identify subsets of patients who might benefit most from the treatment of ADT with or without darolutamide.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Prostate Carcinoma</condition>
  <arm_group>
    <arm_group_label>Arm A (ADT, placebo)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive goserelin acetate, leuprolide acetate, or triptorelin via injection every 3 months for 12 months (4 injections), every 4 months for 12 months (3 injections), or every month for 12 months (12 injections) in the absence of disease progression or unacceptable toxicity. Patients also receive a placebo four times daily (QID) for 52 weeks in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B (ADT, darolutamide)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive goserelin acetate, leuprolide acetate, or triptorelin via injection every 3 months for 12 months (4 injections), every 4 months for 12 months (3 injections), or every month for 12 months (12 injections) in the absence of disease progression or unacceptable toxicity. Patients also receive darolutamide QID for 52 weeks in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Darolutamide</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm B (ADT, darolutamide)</arm_group_label>
    <other_name>Antiandrogen ODM-201</other_name>
    <other_name>BAY 1841788</other_name>
    <other_name>BAY-1841788</other_name>
    <other_name>BAY1841788</other_name>
    <other_name>ODM 201</other_name>
    <other_name>ODM-201</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Goserelin Acetate</intervention_name>
    <description>Given via injection</description>
    <arm_group_label>Arm A (ADT, placebo)</arm_group_label>
    <arm_group_label>Arm B (ADT, darolutamide)</arm_group_label>
    <other_name>ZDX</other_name>
    <other_name>Zoladex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leuprolide Acetate</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm A (ADT, placebo)</arm_group_label>
    <arm_group_label>Arm B (ADT, darolutamide)</arm_group_label>
    <other_name>A-43818</other_name>
    <other_name>Abbott 43818</other_name>
    <other_name>Abbott-43818</other_name>
    <other_name>Carcinil</other_name>
    <other_name>Depo-Eligard</other_name>
    <other_name>Eligard</other_name>
    <other_name>Enanton</other_name>
    <other_name>Enantone</other_name>
    <other_name>Enantone-Gyn</other_name>
    <other_name>Ginecrin</other_name>
    <other_name>LEUP</other_name>
    <other_name>Leuplin</other_name>
    <other_name>Leuprorelin Acetate</other_name>
    <other_name>Lucrin</other_name>
    <other_name>Lucrin Depot</other_name>
    <other_name>Lupron</other_name>
    <other_name>Lupron Depot</other_name>
    <other_name>Lupron Depot-3 Month</other_name>
    <other_name>Lupron Depot-4 Month</other_name>
    <other_name>Lupron Depot-Ped</other_name>
    <other_name>Lutrate</other_name>
    <other_name>Procren</other_name>
    <other_name>Procrin</other_name>
    <other_name>Prostap</other_name>
    <other_name>TAP-144</other_name>
    <other_name>Trenantone</other_name>
    <other_name>Uno-Enantone</other_name>
    <other_name>Viadur</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Administration</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm A (ADT, placebo)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Quality-of-Life Assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Arm A (ADT, placebo)</arm_group_label>
    <arm_group_label>Arm B (ADT, darolutamide)</arm_group_label>
    <other_name>Quality of Life Assessment</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Triptorelin</intervention_name>
    <description>Given via injection</description>
    <arm_group_label>Arm A (ADT, placebo)</arm_group_label>
    <arm_group_label>Arm B (ADT, darolutamide)</arm_group_label>
    <other_name>6-D-Tryptophan-LH-RH</other_name>
    <other_name>6-D-Tryptophanluteinizing Hormone-releasing Factor</other_name>
    <other_name>AY-25650</other_name>
    <other_name>CL-118,532</other_name>
    <other_name>Detryptoreline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  PRE-REGISTRATION INCLUSION (STEP 0)&#xD;
&#xD;
          -  Patient must have undergone a radical prostatectomy (RP) and must be registered to&#xD;
             step 0 of this study at least 6 weeks after but not more than 16 weeks after their&#xD;
             radical prostatectomy&#xD;
&#xD;
          -  Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of&#xD;
             0- 2&#xD;
&#xD;
          -  Patient with a prior or concurrent malignancy within 5 years of registration, whose&#xD;
             natural history or treatment does not have the potential to interfere with the safety&#xD;
             or efficacy assessment of the investigational regimen are eligible for this trial&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral&#xD;
             therapy with undetectable viral load within 6 months are eligible for this trial&#xD;
&#xD;
          -  For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral&#xD;
             load must be undetectable on suppressive therapy, if indicated&#xD;
&#xD;
          -  Patients with a history of hepatitis C virus (HCV) infection must have been treated&#xD;
             and cured. For patients with HCV infection who are currently on treatment, they are&#xD;
             eligible if they have an undetectable HCV viral load&#xD;
&#xD;
          -  For patients with no previous Decipher score: Tumor tissue specimen from prostatectomy&#xD;
             must be available and ready to be shipped&#xD;
&#xD;
          -  INCLUSION CRITERIA FOR RANDOMIZATION (STEP 1)&#xD;
&#xD;
          -  For patients who have previously had Decipher score performed by Decipher Biosciences,&#xD;
             they must have score of &gt;= 0.6&#xD;
&#xD;
          -  For patients who did not have a Decipher score previously performed by Decipher&#xD;
             Biosciences, they must have had a Decipher score of &gt;= 0.6 assessed from the&#xD;
             prostatectomy specimen submitted&#xD;
&#xD;
          -  For patients who did not have a Decipher score previously performed by Decipher&#xD;
             Biosciences, patients must also have a CAPRA-S score &gt;= 3. The CAPRA-S score is&#xD;
             calculated by assigning points for PSA in ng/mL, surgical margin status, seminal&#xD;
             vesicle invasion, and extra-capsular extension. Lymph node involvement will serve as&#xD;
             an exclusion criteria and will not count towards CAPRA-S inclusion score. A CAPRA-S&#xD;
             score is not required for patients who had a Decipher score previously performed by&#xD;
             Decipher Biosciences&#xD;
&#xD;
          -  Patient must have an undetectable PSA (&lt; 0.2ng/mL) obtained within 2 weeks prior to&#xD;
             randomization&#xD;
&#xD;
          -  Leukocytes &gt;= 3,000/mcL (obtained within 4 weeks prior to registration)&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1,000/mcL (obtained within 4 weeks prior to registration)&#xD;
&#xD;
          -  Platelets &gt;= 75,000/mcL (obtained within 4 weeks prior to registration)&#xD;
&#xD;
          -  Total bilirubin =&lt; institutional upper limit of normal (ULN) (obtained within 4 weeks&#xD;
             prior to registration)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase&#xD;
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])&#xD;
             =&lt; 2.5 x institutional ULN (obtained within 4 weeks prior to registration)&#xD;
&#xD;
          -  Glomerular filtration rate (GFR) &gt;= 30 mL/min/1.73 m^2 (obtained within 4 weeks prior&#xD;
             to registration)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  PRE-REGISTRATION EXCLUSION (STEP 0)&#xD;
&#xD;
          -  Patient must not have any previous treatment with androgen deprivation therapy (ADT),&#xD;
             chemotherapy, or other physician prescribed systemic therapy for treatment of their&#xD;
             prostate cancer&#xD;
&#xD;
          -  Patient must not have pathologic evidence of pelvic lymph node involvement&#xD;
&#xD;
          -  Patient must not have an uncontrolled intercurrent illness including, but not limited&#xD;
             to, ongoing or active infection, symptomatic congestive heart failure (New York Heart&#xD;
             Association class III and IV heart failure), unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements&#xD;
&#xD;
          -  EXCLUSION CRITERIA FOR RANDOMIZATION (STEP 1)&#xD;
&#xD;
          -  Patient must not have pre or post-operative radiographic evidence of cancer recurrence&#xD;
             or metastasis by abdominal and pelvic imaging (computed tomography [CT]&#xD;
             abdomen/pelvis, whole body magnetic resonance imaging [MRI], MRI abdomen/pelvis, or&#xD;
             equivalent, AND bone scan) which must be done before or after prostatectomy prior to&#xD;
             randomization. If pre-operative risk does not indicate a need for bone scan,&#xD;
             post-operative Decipher score of &gt;= 0.6 indicates increased risk of metastatic disease&#xD;
             and may be used to obtain CT abdomen/pelvis and bone scan prior to randomization&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alicia K Morgans</last_name>
    <role>Principal Investigator</role>
    <affiliation>ECOG-ACRIN Cancer Research Group</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope Comprehensive Cancer Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Los Angeles County-USC Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>USC / Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford Cancer Institute Palo Alto</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Palo Alto Health Care System</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope South Pasadena</name>
      <address>
        <city>South Pasadena</city>
        <state>California</state>
        <zip>91030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope Upland</name>
      <address>
        <city>Upland</city>
        <state>California</state>
        <zip>91786</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hartford Hospital</name>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <zip>06102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GenesisCare USA - Lakewood Ranch</name>
      <address>
        <city>Lakewood Ranch</city>
        <state>Florida</state>
        <zip>34202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Medical Center</name>
      <address>
        <city>Miami Beach</city>
        <state>Florida</state>
        <zip>33140</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GenesisCare USA - Plantation</name>
      <address>
        <city>Plantation</city>
        <state>Florida</state>
        <zip>33324</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pali Momi Medical Center</name>
      <address>
        <city>'Aiea</city>
        <state>Hawaii</state>
        <zip>96701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hawaii Cancer Care Inc - Waterfront Plaza</name>
      <address>
        <city>Honolulu</city>
        <state>Hawaii</state>
        <zip>96813</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen's Cancer Cenrer - POB I</name>
      <address>
        <city>Honolulu</city>
        <state>Hawaii</state>
        <zip>96813</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen's Medical Center</name>
      <address>
        <city>Honolulu</city>
        <state>Hawaii</state>
        <zip>96813</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Straub Clinic and Hospital</name>
      <address>
        <city>Honolulu</city>
        <state>Hawaii</state>
        <zip>96813</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen's Cancer Center - Kuakini</name>
      <address>
        <city>Honolulu</city>
        <state>Hawaii</state>
        <zip>96817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Cancer Center of Hawaii-Liliha</name>
      <address>
        <city>Honolulu</city>
        <state>Hawaii</state>
        <zip>96817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush - Copley Medical Center</name>
      <address>
        <city>Aurora</city>
        <state>Illinois</state>
        <zip>60504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare-Bloomington</name>
      <address>
        <city>Bloomington</city>
        <state>Illinois</state>
        <zip>61704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare-Canton</name>
      <address>
        <city>Canton</city>
        <state>Illinois</state>
        <zip>61520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare-Carthage</name>
      <address>
        <city>Carthage</city>
        <state>Illinois</state>
        <zip>62321</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago Comprehensive Cancer Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carle on Vermilion</name>
      <address>
        <city>Danville</city>
        <state>Illinois</state>
        <zip>61832</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Care Specialists of Illinois - Decatur</name>
      <address>
        <city>Decatur</city>
        <state>Illinois</state>
        <zip>62526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Decatur Memorial Hospital</name>
      <address>
        <city>Decatur</city>
        <state>Illinois</state>
        <zip>62526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carle Physician Group-Effingham</name>
      <address>
        <city>Effingham</city>
        <state>Illinois</state>
        <zip>62401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Crossroads Cancer Center</name>
      <address>
        <city>Effingham</city>
        <state>Illinois</state>
        <zip>62401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Elmhurst Memorial Hospital</name>
      <address>
        <city>Elmhurst</city>
        <state>Illinois</state>
        <zip>60126</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare-Eureka</name>
      <address>
        <city>Eureka</city>
        <state>Illinois</state>
        <zip>61530</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NorthShore University HealthSystem-Evanston Hospital</name>
      <address>
        <city>Evanston</city>
        <state>Illinois</state>
        <zip>60201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare-Galesburg</name>
      <address>
        <city>Galesburg</city>
        <state>Illinois</state>
        <zip>61401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NorthShore University HealthSystem-Glenbrook Hospital</name>
      <address>
        <city>Glenview</city>
        <state>Illinois</state>
        <zip>60026</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NorthShore University HealthSystem-Highland Park Hospital</name>
      <address>
        <city>Highland Park</city>
        <state>Illinois</state>
        <zip>60035</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare-Kewanee Clinic</name>
      <address>
        <city>Kewanee</city>
        <state>Illinois</state>
        <zip>61443</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern Medicine Lake Forest Hospital</name>
      <address>
        <city>Lake Forest</city>
        <state>Illinois</state>
        <zip>60045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare-Macomb</name>
      <address>
        <city>Macomb</city>
        <state>Illinois</state>
        <zip>61455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carle Physician Group-Mattoon/Charleston</name>
      <address>
        <city>Mattoon</city>
        <state>Illinois</state>
        <zip>61938</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Edward Hospital/Cancer Center</name>
      <address>
        <city>Naperville</city>
        <state>Illinois</state>
        <zip>60540</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC Comprehensive Cancer Center at Silver Cross</name>
      <address>
        <city>New Lenox</city>
        <state>Illinois</state>
        <zip>60451</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare-Ottawa Clinic</name>
      <address>
        <city>Ottawa</city>
        <state>Illinois</state>
        <zip>61350</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare-Pekin</name>
      <address>
        <city>Pekin</city>
        <state>Illinois</state>
        <zip>61554</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare-Peoria</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Methodist Medical Center of Illinois</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61636</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare-Peru</name>
      <address>
        <city>Peru</city>
        <state>Illinois</state>
        <zip>61354</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare-Princeton</name>
      <address>
        <city>Princeton</city>
        <state>Illinois</state>
        <zip>61356</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Illinois University School of Medicine</name>
      <address>
        <city>Springfield</city>
        <state>Illinois</state>
        <zip>62702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Springfield Clinic</name>
      <address>
        <city>Springfield</city>
        <state>Illinois</state>
        <zip>62702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Medical Center</name>
      <address>
        <city>Springfield</city>
        <state>Illinois</state>
        <zip>62781</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carle Cancer Center</name>
      <address>
        <city>Urbana</city>
        <state>Illinois</state>
        <zip>61801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Carle Foundation Hospital</name>
      <address>
        <city>Urbana</city>
        <state>Illinois</state>
        <zip>61801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare - Washington</name>
      <address>
        <city>Washington</city>
        <state>Illinois</state>
        <zip>61571</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University/Melvin and Bren Simon Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Oncology and Hematology Associates-West Des Moines</name>
      <address>
        <city>Clive</city>
        <state>Iowa</state>
        <zip>50325</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Iowa Methodist Medical Center</name>
      <address>
        <city>Des Moines</city>
        <state>Iowa</state>
        <zip>50309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Oncology and Hematology Associates-Des Moines</name>
      <address>
        <city>Des Moines</city>
        <state>Iowa</state>
        <zip>50309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Broadlawns Medical Center</name>
      <address>
        <city>Des Moines</city>
        <state>Iowa</state>
        <zip>50314</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mission Cancer and Blood - Laurel</name>
      <address>
        <city>Des Moines</city>
        <state>Iowa</state>
        <zip>50314</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Iowa Lutheran Hospital</name>
      <address>
        <city>Des Moines</city>
        <state>Iowa</state>
        <zip>50316</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Methodist West Hospital</name>
      <address>
        <city>West Des Moines</city>
        <state>Iowa</state>
        <zip>50266-7700</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University/Sidney Kimmel Cancer Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beverly Hospital</name>
      <address>
        <city>Beverly</city>
        <state>Massachusetts</state>
        <zip>01915</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lahey Hospital and Medical Center</name>
      <address>
        <city>Burlington</city>
        <state>Massachusetts</state>
        <zip>01805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Addison Gilbert Hospital</name>
      <address>
        <city>Gloucester</city>
        <state>Massachusetts</state>
        <zip>01930</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lahey Medical Center-Peabody</name>
      <address>
        <city>Peabody</city>
        <state>Massachusetts</state>
        <zip>01960</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Winchester Hospital</name>
      <address>
        <city>Winchester</city>
        <state>Massachusetts</state>
        <zip>01890</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GenesisCare USA - Clarkston</name>
      <address>
        <city>Clarkston</city>
        <state>Michigan</state>
        <zip>48346</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GenesisCare USA - Farmington Hills</name>
      <address>
        <city>Farmington Hills</city>
        <state>Michigan</state>
        <zip>48334</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GenesisCare USA - Macomb</name>
      <address>
        <city>Macomb</city>
        <state>Michigan</state>
        <zip>48044</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GenesisCare USA - Madison Heights</name>
      <address>
        <city>Madison Heights</city>
        <state>Michigan</state>
        <zip>48071</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>William Beaumont Hospital-Royal Oak</name>
      <address>
        <city>Royal Oak</city>
        <state>Michigan</state>
        <zip>48073</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>William Beaumont Hospital - Troy</name>
      <address>
        <city>Troy</city>
        <state>Michigan</state>
        <zip>48085</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GenesisCare USA - Troy</name>
      <address>
        <city>Troy</city>
        <state>Michigan</state>
        <zip>48098</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Unity Hospital</name>
      <address>
        <city>Fridley</city>
        <state>Minnesota</state>
        <zip>55432</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minnesota Oncology Hematology PA-Maplewood</name>
      <address>
        <city>Maplewood</city>
        <state>Minnesota</state>
        <zip>55109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regions Hospital</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Francis Medical Center</name>
      <address>
        <city>Cape Girardeau</city>
        <state>Missouri</state>
        <zip>63703</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Hospital Saint Louis</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bozeman Deaconess Hospital</name>
      <address>
        <city>Bozeman</city>
        <state>Montana</state>
        <zip>59715</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Benefis Healthcare- Sletten Cancer Institute</name>
      <address>
        <city>Great Falls</city>
        <state>Montana</state>
        <zip>59405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Hampshire Oncology Hematology PA-Concord</name>
      <address>
        <city>Concord</city>
        <state>New Hampshire</state>
        <zip>03301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Solinsky Center for Cancer Care</name>
      <address>
        <city>Manchester</city>
        <state>New Hampshire</state>
        <zip>03103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center-Einstein Campus</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest University at Clemmons</name>
      <address>
        <city>Clemmons</city>
        <state>North Carolina</state>
        <zip>27012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest University Health Sciences</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Bismarck Medical Center</name>
      <address>
        <city>Bismarck</city>
        <state>North Dakota</state>
        <zip>58501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Broadway Medical Center</name>
      <address>
        <city>Fargo</city>
        <state>North Dakota</state>
        <zip>58122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Roger Maris Cancer Center</name>
      <address>
        <city>Fargo</city>
        <state>North Dakota</state>
        <zip>58122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati Cancer Center-UC Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Toledo</name>
      <address>
        <city>Toledo</city>
        <state>Ohio</state>
        <zip>43614</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati Cancer Center-West Chester</name>
      <address>
        <city>West Chester</city>
        <state>Ohio</state>
        <zip>45069</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Genesis Healthcare System Cancer Care Center</name>
      <address>
        <city>Zanesville</city>
        <state>Ohio</state>
        <zip>43701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Oklahoma Health Sciences Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Medical Center</name>
      <address>
        <city>Danville</city>
        <state>Pennsylvania</state>
        <zip>17822</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Penn State Milton S Hershey Medical Center</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033-0850</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Reading Hospital</name>
      <address>
        <city>West Reading</city>
        <state>Pennsylvania</state>
        <zip>19611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Wyoming Valley/Henry Cancer Center</name>
      <address>
        <city>Wilkes-Barre</city>
        <state>Pennsylvania</state>
        <zip>18711</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ralph H Johnson VA Medical Center</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkland Memorial Hospital</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Southwestern/Simmons Cancer Center-Dallas</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Southwestern/Simmons Cancer Center-Fort Worth</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Southwestern Clinical Center at Richardson/Plano</name>
      <address>
        <city>Richardson</city>
        <state>Texas</state>
        <zip>75080</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Audie L Murphy VA Hospital</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Health Science Center at San Antonio</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Commonwealth University/Massey Cancer Center</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Medical Center-EC Cancer Center</name>
      <address>
        <city>Eau Claire</city>
        <state>Wisconsin</state>
        <zip>54701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>William S Middleton VA Medical Center</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin Carbone Cancer Center</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Medical Center-Marshfield</name>
      <address>
        <city>Marshfield</city>
        <state>Wisconsin</state>
        <zip>54449</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Clinic-Minocqua Center</name>
      <address>
        <city>Minocqua</city>
        <state>Wisconsin</state>
        <zip>54548</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Medical Center-Rice Lake</name>
      <address>
        <city>Rice Lake</city>
        <state>Wisconsin</state>
        <zip>54868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Medical Center-River Region at Stevens Point</name>
      <address>
        <city>Stevens Point</city>
        <state>Wisconsin</state>
        <zip>54482</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Medical Center - Weston</name>
      <address>
        <city>Weston</city>
        <state>Wisconsin</state>
        <zip>54476</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 21, 2020</study_first_submitted>
  <study_first_submitted_qc>July 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>June 21, 2023</last_update_submitted>
  <last_update_submitted_qc>June 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leuprolide</mesh_term>
    <mesh_term>Goserelin</mesh_term>
    <mesh_term>Triptorelin Pamoate</mesh_term>
    <mesh_term>Tryptophan</mesh_term>
    <mesh_term>Androgen Antagonists</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04484818
org study id: EA8183
secondary id: NCI-2020-02383
secondary id: EA8183
secondary id: EA8183
secondary id: U10CA180820
nct id: NCT04484818
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase III trial compares the effect of adding darolutamide to ADT versus ADT alone after
      surgery for the treatment of high-risk prostate cancer. ADT reduces testosterone levels in
      the blood. Testosterone is a hormone made mainly in the testes and is needed to develop and
      maintain male sex characteristics, such as facial hair, deep voice, and muscle growth. It
      also plays role in prostate cancer development. Darolutamide blocks the actions of the
      androgens (e.g. testosterone) in the tumor cells and in the body. Giving darolutamide with
      ADT may work better in eliminating or reducing the size of the cancer and/or prevent it from
      returning compared to ADT alone in patients with prostate cancer.
PRIMARY OBJECTIVE:

      I. To determine whether 12 months of androgen deprivation therapy (ADT) and darolutamide
      improves metastasis-free survival (MFS) compared to 12 months of ADT plus placebo in men with
      high risk prostate cancer (defined by Cancer of the Prostate Risk Assessment Post-surgical
      [CAPRA-S] score >= 3 and a high Decipher score (>= 0.6) [C3+D+]) who have undergone radical
      prostatectomy.

      SECONDARY OBJECTIVES:

      I. To determine whether 12 months of ADT and darolutamide improves recurrence-free survival
      (RFS) compared to 12 months of ADT plus placebo in men with high-risk prostate cancer that
      have undergone radical prostatectomy.

      II. To determine whether 12 months of ADT and darolutamide improves event-free survival (EFS)
      compared to 12 months of ADT plus placebo in men with high-risk prostate cancer that have
      undergone radical prostatectomy.

      III. To determine whether 12 months of ADT and darolutamide improves overall survival (OS)
      compared to 12 months of ADT plus placebo in men with high-risk prostate cancer that have
      undergone radical prostatectomy.

      IV. To determine the rate of testosterone recovery and time to testosterone recovery in each
      treatment arm.

      V. To evaluate the safety and tolerability of ADT and darolutamide.

      CORRELATIVE OBJECTIVES FOR EXPLORATORY BIOMARKERS:

      I. To discover a novel gene expression signature in the Decipher transcriptome platforms that
      is predictive of clinical outcome, as defined by the primary and secondary objectives of this
      study, in response to ADT by intensification with darolutamide versus ADT alone.

      II. To assess the prevalence of subclasses of established transcriptome expression signatures
      and prospectively validate their predictive value for ADT response, these include: (i)
      androgen (AR) activity (ii) Basal-luminal subtyping based on modified PAM50, and (iii) ADT
      score.

      III. To assess whether the spectrum of high Decipher scores (0.6-1.0), prostate-specific
      antigen (PSA) levels at presentation and post-radical prostatectomy (RP) and final pathology
      variables affect the response and outcome to ADT and darolutamide.

      QUALITY OF LIFE (QOL) OBJECTIVES:

      I. To compare overall quality of life, measured by Functional Assessment of Cancer
      Therapy-Prostate (FACT-P) total score, at 18 months between the two arms. (Primary) II. To
      compare the change in overall quality of life, measured by FACT-P total score, from baseline
      to 18 months between the two arms. (Secondary) III. To compare patient-reported fatigue
      (Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue scores) at 12 months
      between the two treatment arms. (Secondary) IV. To compare the change in subjective
      patient-reported cognitive function (FACT-Cognitive [Cog]) from baseline to 12 months between
      the treatment arms. (Exploratory) V. To compare subjective patient-reported cognitive
      function (FACT-Cog scores) at 12 months between the two treatment arms. (Exploratory)

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Patients receive goserelin acetate, leuprolide acetate, or triptorelin via injection
      every 3 months for 12 months (4 injections), every 4 months for 12 months (3 injections), or
      every month for 12 months (12 injections) in the absence of disease progression or
      unacceptable toxicity. Patients also receive a placebo four times daily (QID) for 52 weeks in
      the absence of disease progression or unacceptable toxicity.

      ARM II: Patients receive goserelin acetate, leuprolide acetate, or triptorelin via injection
      every 3 months for 12 months (4 injections), every 4 months for 12 months (3 injections), or
      every month for 12 months (12 injections) in the absence of disease progression or
      unacceptable toxicity. Patients also receive darolutamide QID for 52 weeks in the absence of
      disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 36 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Metastasis-free survival (MFS)
time frame: From randomization to development of metastatic disease or death, whichever occurs first, assessed up to 36 months
description: The primary comparison will be an intention-to-treat analysis of all randomized patients. The method of Kaplan and Meier will be used to characterize the time-to-event endpoints, and a logrank test will be used to compare these endpoints across treatments.
measure: Recurrence-free survival (RFS)
time frame: From randomization to any of the MFS events, pelvic lymph node recurrence or detectable prostate-specific antigen (PSA) (PSA >= 0.2 ng/mL, confirmed by a second PSA of the same level or higher), whichever occurs first, assessed up to 36 months
description: The method of Kaplan and Meier will be used to characterize the time-to-event endpoints, and a logrank test will be used to compare these endpoints across treatments.
measure: Event-free survival
time frame: From randomization to any of the RFS events, treatment with salvage radiation therapy with or without systemic therapy, or initiation of systemic therapy for presumed recurrence, whichever occurs first, assessed up to 36 months
description: The method of Kaplan and Meier will be used to characterize the time-to-event endpoints, and a logrank test will be used to compare these endpoints across treatments.
measure: Overall survival
time frame: From randomization to death by any cause or date last known alive, assessed up to 36 months
description: The method of Kaplan and Meier will be used to characterize the time-to-event endpoints, and a logrank test will be used to compare these endpoints across treatments.
measure: Testosterone recovery rate
time frame: At time of disease progression, assessed up to 36 months
description: Exact binomial confidence intervals will be used to describe the proportions of patients with testosterone recovery in each arm.
measure: Time to testosterone recovery
time frame: From randomization to a return of serum testosterone level to greater than or equal to lower limit of normal for the testosterone assay, assessed up to 36 months
description: The method of Kaplan and Meier will be used to characterize the time-to-event endpoints, and a logrank test will be used to compare these endpoints across treatments.
measure: Incidence of adverse events
time frame: Up to 78 weeks
description: Toxicity will be defined using the Common Terminology Criteria for Adverse Events version 5.0.
measure: Change in quality of life: Functional Assessment of Cancer Therapy (FACT)
time frame: Baseline up to 18 months
description: Will be assessed by the Functional Assessment of Cancer Therapy (FACT) - Prostate, FACT - Cognitive, and Functional Assessment of Chronic Illness Therapy - Fatigue. Fatigue instruments at baseline, 6, 12 and 18 months, and descriptive statistics will be used to characterize quality of life over time in each arm. Each item is answered on a 5-point Likert-type scale, where a value of 0 indicates the statement is not applicable, and a value of 5 indicates the statement is applicable to the respondent. Subgroup analysis will be performed among patients who receive adjuvant radiation therapy and patients who do not receive adjuvant radiation therapy in each arm. Mixed effect models will be constructed as an exploratory analysis to estimate the time profile of quality of life assessments in the two arms and to evaluate treatment-by-time interactions.
measure: Overall quality of life: Functional Assessment of Cancer Therapy (FACT)
time frame: At 18 months
description: Will be assessed by the Functional Assessment of Cancer Therapy (FACT) - Prostate total score. The total score can range from 0 to 156, where a higher value indicates a better quality of life. Mixed effect models will be constructed as an exploratory analysis to estimate the time profile of quality of life assessments in the two arms and to evaluate treatment-by-time interactions.
measure: Change in Functional Assessment of Cancer Therapy (FACT) - Prostate score
time frame: Baseline up to 18 months
description: A paired t test will be used to compare Functional Assessment of Cancer Therapy (FACT) - Prostate scores at these two time points in each arm. The total score can range from 0 to 156, where a higher value indicates a better quality of life. A two-sample t test will be performed to compare the changes in FACT - Prostate scores from baseline to 18 months between the two arms. Mixed effect models will be constructed as an exploratory analysis to estimate the time profile of quality of life assessments in the two arms and to evaluate treatment-by-time interactions.
measure: Cognitive function
time frame: At 12 months (completion of treatment)
description: Will be measured between the two arms by Functional Assessment of Cancer Therapy (FACT) - Cognitive. The FACT-Cognitive has four subscales: perceived cognitive impairments (PCI), perceived cognitive abilities, impact of perceived cognitive impairment on quality of life, and comments from others on cognitive function. Summary statistics will be used to describe each subscale at each time point and the PCI subscale score, which ranges from 0-72, where higher values indicate better quality of life, at 12 months will be the primary measurement of this analysis. Bonferroni correction will be employed for the 3 follow-up time points of interest (6, 12, and 18 months) to make the analysis conservative. Mixed effect models will be constructed as an exploratory analysis to estimate the time profile of quality of lifeassessments in the two arms and to evaluate treatment-by-time interactions.
measure: Change in cognitive function
time frame: Baseline up to 12 months (completion of treatment)
description: Will be measured between the two arms by Functional Assessment of Cancer Therapy (FACT) - Cognitive. The FACT-Cognitive has four subscales: perceived cognitive impairments (PCI), perceived cognitive abilities, impact of perceived cognitive impairment on quality of life, and comments from others on cognitive function. Summary statistics will be used to describe each subscale at each time point and the PCI subscale score, which ranges from 0-72, where higher values indicate better quality of life, at 12 months will be the primary measurement of this analysis. Bonferroni correction will be employed for the 3 follow-up time points of interest (6, 12, and 18 months) to make the analysis conservative. Mixed effect models will be constructed as an exploratory analysis to estimate the time profile of quality of life assessments in the two arms and to evaluate treatment-by-time interactions.
measure: Identification of novel gene expression signatures
time frame: Up to 36 months
description: The associations between the gene expression signatures and clinical outcomes will be assessed by Cox proportional hazards models and logrank test.
measure: Prognostic value of established signatures
time frame: Up to 36 months
description: Will include androgen receptor activity, basal-luminal subtyping by modified PAM50 and androgen deprivation therapy score using Cox proportional hazards models. Similar analysis will be performed to evaluate the prognostic value of luminal-basal subtype. The treatment-by-subtype interaction will also be assessed. For androgen deprivation therapy score, patients will be categorized into either low or high androgen deprivation therapy score using a cutoff of 0.36.
measure: Decipher scores
time frame: Up to 36 months
description: Will be associated with MFS as well as disease characteristics. Cox proportional hazards models will be performed with adjustment for important disease characteristics, including prostate-specific antigen, Gleason score, disease stage, pathology of the radical prostatectomy specimen, etc. Decipher score could be categorized into a few risk groups and the Akaike information criterion method will be used to determine the optimal number of cutoff points. To assess whether treatment effect is affected by Decipher score levels, the treatment-by-Decipher interactions will be included in the model as well. Decipher scores range from 0.00 to 1.00, where higher values indicate higher risk disease.
measure: Genome-wide alterations
time frame: Up to 36 months
description: Prostate cancer specimens will be banked for future studies to perform genome-wide alterations in coding and non-coding deoxyribonucleic acid sequences. To identify the genetic alterations that are associated with development of metastasis, Cox proportional hazards models and logrank test will be used. The analysis will focus on actionable alterations first. The treatment-by-alteration interactions will also be assessed to determine whether response to darolutamide is affected by distinct genomic subgroups. Ultimately the findings on gene expression signatures and deoxyribonucleic acid alterations will be assessed in the models simultaneously to identify subsets of patients who might benefit most from the treatment of ADT with or without darolutamide.
arm group label: Arm A (ADT, placebo)
arm group type: Active Comparator
description: Patients receive goserelin acetate, leuprolide acetate, or triptorelin via injection every 3 months for 12 months (4 injections), every 4 months for 12 months (3 injections), or every month for 12 months (12 injections) in the absence of disease progression or unacceptable toxicity. Patients also receive a placebo four times daily (QID) for 52 weeks in the absence of disease progression or unacceptable toxicity.
arm group label: Arm B (ADT, darolutamide)
arm group type: Experimental
description: Patients receive goserelin acetate, leuprolide acetate, or triptorelin via injection every 3 months for 12 months (4 injections), every 4 months for 12 months (3 injections), or every month for 12 months (12 injections) in the absence of disease progression or unacceptable toxicity. Patients also receive darolutamide QID for 52 weeks in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Darolutamide
description: Given PO
arm group label: Arm B (ADT, darolutamide)
other name: Antiandrogen ODM-201
other name: BAY 1841788
other name: BAY-1841788
other name: BAY1841788
other name: ODM 201
other name: ODM-201
intervention type: Drug
intervention name: Goserelin Acetate
description: Given via injection
arm group label: Arm A (ADT, placebo)
arm group label: Arm B (ADT, darolutamide)
other name: ZDX
other name: Zoladex
intervention type: Drug
intervention name: Leuprolide Acetate
description: Given IV
arm group label: Arm A (ADT, placebo)
arm group label: Arm B (ADT, darolutamide)
other name: A-43818
other name: Abbott 43818
other name: Abbott-43818
other name: Carcinil
other name: Depo-Eligard
other name: Eligard
other name: Enanton
other name: Enantone
other name: Enantone-Gyn
other name: Ginecrin
other name: LEUP
other name: Leuplin
other name: Leuprorelin Acetate
other name: Lucrin
other name: Lucrin Depot
other name: Lupron
other name: Lupron Depot
other name: Lupron Depot-3 Month
other name: Lupron Depot-4 Month
other name: Lupron Depot-Ped
other name: Lutrate
other name: Procren
other name: Procrin
other name: Prostap
other name: TAP-144
other name: Trenantone
other name: Uno-Enantone
other name: Viadur
intervention type: Drug
intervention name: Placebo Administration
description: Given PO
arm group label: Arm A (ADT, placebo)
intervention type: Other
intervention name: Quality-of-Life Assessment
description: Ancillary studies
arm group label: Arm A (ADT, placebo)
arm group label: Arm B (ADT, darolutamide)
other name: Quality of Life Assessment
intervention type: Drug
intervention name: Triptorelin
description: Given via injection
arm group label: Arm A (ADT, placebo)
arm group label: Arm B (ADT, darolutamide)
other name: 6-D-Tryptophan-LH-RH
other name: 6-D-Tryptophanluteinizing Hormone-releasing Factor
other name: AY-25650
other name: CL-118,532
other name: Detryptoreline
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alicia K Morgans
role: Principal Investigator
affiliation: ECOG-ACRIN Cancer Research Group
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country: United States
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Leuprolide
mesh term: Goserelin
mesh term: Triptorelin Pamoate
mesh term: Tryptophan
mesh term: Androgen Antagonists