CLINICAL TRIAL / NCT03141671

Inclusion Criteria: - Histologically confirmed prostate cancer - PSA ≥ 0.1 after radical prostatectomy (value w/in 3 months of registration) AND at least 1 unfavorable risk factor listed below. - Gleason 8-10 - PSA > 0.5 - Pathologically positive lymph nodes - pT3 or pT4 - PSA doubling time (DT) < 10 months - Negative margins - Persistent PSA after 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 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 - ECOG Performance Status ≤ 2 (Appendix A) - Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 3 months of registration. - System Laboratory Value - Hematological: - Platelet count (plt) ≥ 100,000/ µL - Hemoglobin (Hgb) ≥ 9 g/dL - Absolute neutrophil count (ANC) ≥ 1000 cells/µL - Renal: --GFR1 ≥ 45 mL/min - Hepatic and Other: - Bilirubin2 ≤ 1.5 × upper limit of normal (ULN) - Aspartate aminotransferase (AST) ≤ 2.5 × ULN - Alanine aminotransferase (ALT) ≤ 2.5 × ULN - Serum Albumin > 3.0 g/dL - Serum potassium ≥ 3.5 mmol/L - Coagulation: - International Normalized Ratio (INR) - or Prothrombin Time (PT) - Activated Partial Thromboplastin Time - (aPTT) ≤ 1.5 × ULN (unless on prophylactic or therapeutic dosing with low molecular weight heparin) - Cockcroft-Gault formula will be used to calculate creatinine clearance (see study procedure manual SPM) - In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin; if direct bilirubin is ≤1.5 × ULN, subject may be eligible - 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 (see list under prohibited meds) must be discontinued or substituted at least 4 weeks prior to study entry (Section 5.5) - Use of CYP3A4 inhibitors or inducers and CYP2D6 substrates must be discontinued prior to study entry - Able to swallow pills Exclusion Criteria: - Use of post-prostatectomy ADT for > 30 continuous days prior to registration (ADT defined as use of 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 unless additional radiation can be safely delivered according to the treating physician - 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 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