Testing the Addition of the Drug Apalutamide to the Usual Hormone Therapy and Radiation Therapy After Surgery for Prostate Cancer

Primary Outcome Measures:

  1. Metastasis-free survival (MFS) [Time Frame: From randomization to detection of metastatic disease or death from any cause, assessed up to 7.5 years]

    Kaplan-Meier curves will be generated and metastasis-free survival compared between the two treatment groups by a logrank test, stratified by prostate specific antigen (PSA) level after prostatectomy (never detectable or rising). Cox regression modeling to assess and adjust for the effects of PSA stratum and other baseline covariates will also be performed. The proportional hazards assumption will be tested using Schoenfeld residuals and graphical methods. Martingale residual plots will be examined to determine the best functional form for incorporating covariates into the model. A competing risks analysis will also be performed with time to distant metastasis or death from prostate cancer as the event of interest and death from other causes as the competing risk. Cumulative incidence curves will be generated along with Fine-Gray's test. Patients alive and metastasis free will be censored as of the time of the last negative examination.

Inclusion Criteria:

  • Pathologically (histologically) proven diagnosis of prostate adenocarcinoma. 
  • Any T-stage is eligible 
  • Appropriate stage for study entry based on fluciclovine F-18 positron emission tomography (PET) scan (FACBC, Axumin) within 90 days prior to registration that is negative for distant metastatic (M1a, M1b, M1c) disease
  • Pathologically node positive disease with nodal involvement only in the pelvis in the prostatectomy specimen 
  • History/physical examination within 90 days prior to registration
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 90 days prior to registration
  • Detectable PSA after radical prostatectomy. 
  • Patients who have already started on post-prostatectomy GnRH agonist/antagonist for =< 180 days prior to registration are eligible 
  • Hemoglobin >= 9.0 g/dL, independent of transfusion and/or growth factors (within 90 days prior to registration)
  • Platelet count >= 100,000 x 10^9/uL independent of transfusion and/or growth factors (within 90 days prior to registration)
  • Serum potassium >= 3.5 mmol/L within 90 days prior to registration
  • Creatinine clearance (CrCl) >= 30 mL/min estimated by Cockcroft-Gault 
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 90 days prior to registration)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (within 90 days prior to registration)
  • Serum albumin >= 3.0 g/dL (within 90 days prior to registration)
  • Discontinue or substitute concomitant medications known to lower the seizure threshold at least 30 days prior to registration
  • The patient must agree to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial and have a CD4 count >= 200 cells/microliter within 30 days prior to registration. 
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy within 30 days prior to registration, if indicated. 
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. 
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. 
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

Exclusion Criteria:

  • Definitive radiologic evidence of metastatic disease (M1a, M1b or M1c) on molecular imaging (e.g. fluciclovine F-18 PET, F-18 PSMA, PSMA, F-18 choline 11)
  • Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration)
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • Androgen deprivation therapy (ADT) prior to radical prostatectomy
  • Prior treatment with androgen receptor signaling inhibitor, unless started =< 180 days and stopped prior to registration, which is allowed
  • Current use of 5-alpha reductase inhibitor. 
  • History of any of the following:
    • Seizure or known condition that may pre-dispose to seizure 
    • Severe or unstable angina, myocardial infarction, arterial or venous thromboembolic events, or clinically significant ventricular arrhythmias within 12 months prior to registration
    • New York Heart Association functional classification III/IV 
    • History of any condition that in the opinion of the investigator, would preclude participation in this study
  • Current evidence of any of the following:
    • Known gastrointestinal disorder affecting absorption of oral medications
    • Active uncontrolled infection
    • Presence of uncontrolled hypertension (persistent systolic blood pressure [BP] >= 160 mmHg or diastolic BP >= 100 mmHg). 
    • Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily
    • Baseline moderate and severe hepatic impairment (Child-Pugh Class B & C)
    • Inability to swallow oral pills
    • Any current condition that in the opinion of the investigator, would preclude participation in this study
  • Patients must not plan to participate in any other therapeutic clinical trials while receiving treatment on this study
  • Patients with inflammatory bowel disease
  • Other inclusion/exclusion criteria are present. Please contact the study team for a complete list.
NRG Oncology
Principal Investigator(s)
Yuan James Rao, MD
Contact Phone Number
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