Radiation Therapy and Androgen Deprivation Therapy with or without Abiraterone Acetate and Apalutamide in Treating Patients with Prostate Cancer

Inclusion Criteria

• Histologically confirmed prostate cancer
• PSA >= 0.1 after radical prostatectomy (value w/in 90 days of registration and prior to initiating any ADT) AND at least 1 unfavorable risk factor listed below * Gleason 8-10 * PSA > 0.5 * Pathologically or imaging positive lymph nodes * pT3 or pT4 * PSA doubling time (DT) < 10 months * Negative margins * Persistent PSA after radical prostatectomy (RP) (PSA never dropped below 0.1 after RP) * Local/regional recurrence on imaging * Decipher “high risk” (a Medicare-reimbursed test for risk of metastases after prostatectomy)
• Candidate for salvage radiation and ADT treatment
• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information prior to registration; NOTE: HIPAA authorization may be included in the informed consent or obtained separately; subject must have the ability to understand and willingness to sign the written informed consent document
• 18 =< age =< 95 at the time of consent
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Platelet count (plt) >= 100,000/uL (within 90 days of registration)
• Hemoglobin (Hgb) >= 9 g/dL (within 90 days of registration)
• Absolute neutrophil count (ANC) >= 1000 cells/uL (within 90 days of registration)
• Creatinine clearance >= 45 mL/min; Cockcroft-Gault formula will be used to calculate creatinine clearance (within 90 days of registration)
• Bilirubin =< 1.5 x upper limit of normal (ULN); in subjects with Gilbert’s syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin; if direct bilirubin is =< 1.5 x ULN, subject may be eligible (within 90 days of registration)
• Aspartate aminotransferase (AST) =< 2.5 x ULN (within 90 days of registration)
• Alanine aminotransferase (ALT) =< 2.5 x ULN (within 90 days of registration)
• Serum albumin > 3.0 g/dL (within 90 days of registration)
• Serum potassium >= 3.5 mmol/L (within 90 days of registration)
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN (unless on prophylactic or therapeutic dosing with low molecular weight heparin) (within 90 days of registration)
• Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (unless on prophylactic or therapeutic dosing with low molecular weight heparin) (within 90 days of registration)
• Agrees 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 agrees 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; must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug
• Ability to understand and comply with study procedures for the entire length of the study as determined by the site investigator or protocol designee
• Medications known to lower the seizure threshold must be discontinued or substituted prior to cycle 1 day 1 (C1D1) of study treatment for patients on Arm 2
• Use of CYP3A4 inhibitors or inducers and CYP2D6 substrates must be taken with caution for patients on Arm 2
• Able to swallow pills

Exclusion Criteria

• Use of post-prostatectomy ADT for > 30 continuous days prior to registration (ADT defined as use of gonadotropin-releasing hormone [GnRH] agonist, with or without an anti-androgen). However, patients with testosterone recovery after post-prostatectomy ADT are eligible (testosterone recovery defined as total testosterone > 190 ng/dL) regardless of how long they have been on ADT
• Prior pelvic radiation is not allowed, unless additional radiation can be safely delivered according to the treating investigator
• PSA > 15 ng/mL in screening
• History of any of the following: * Seizure or known condition that may predispose to seizure (e.g., prior stroke within 1 year of randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy) * Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization
• Current evidence of any of the following: * Uncontrolled hypertension * Gastrointestinal disorder affecting absorption * Active infection (e.g., human immunodeficiency virus [HIV] or viral hepatitis) * Any chronic medical condition requiring a dose of corticosteroid higher than 10 mg prednisone/prednisolone once daily * Any condition that, in the opinion of the site investigator, would preclude participation in this study * Moderate or severe hepatic impairment (Child Pugh class B or C)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, psychiatric illness or social situations that would limit compliance with study requirements
• Individuals with a history of another malignancy are not eligible if: * The cancer is under active treatment or * The cancer can be seen on radiology scans or * If they are off cancer treatment but in the opinion of their oncologist have a high risk of relapse within 5 years
• Confirmed bone metastases on imaging