Abiraterone, Enzalutamide, or Apalutamide in Castrate-sensitive Prostate Cancer.

Prior treatment

• Prior cytotoxic chemotherapy, aminoglutethimide, ketoconazole, abiraterone acetate, apalutamide or enzalutamide or darolutamide for the treatment of prostate cancer or participation in a clinical trial of an investigational agent that inhibits the androgen receptor or androgen synthesis (unless treatment was placebo).
• Treatment with hormonal therapy (e.g., androgen receptor inhibitors other than bicalutamide, estrogens, 5-alpha reductase inhibitors) or biologic therapy for prostate cancer (other than approved bone-targeting agents and GnRH agonist/antagonist therapy) within 4 weeks of randomization.
• History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma).
• Patients who are receiving any other investigational agents concurrently.

Other illness

• Clinically significant heart disease as evidenced by New York Heart Association (NYHA) Class III-IV heart disease.

Other

• Subjects with any of the following will not be enrolled:
• Child-Pugh Class B and C

• Veterans must meet the following to be eligible to participate:
• Be willing and able to provide written informed consent for the trial.
• Age ≥18 years of age on day of signing informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less (on a scale from 0 to 5, with higher scores indicating greater disability and a score of 5 indicating death).
• Histologically or cytologically confirmed adenocarcinoma of the prostate without morphologic evidence of small-cell features in either a recently obtained sample or in the archival sample at the time of diagnosis.
• Have previously begun within 120 days of randomization or will receive androgen-deprivation therapy with a gonadotropin releasing hormone agonist or antagonist or have undergone bilateral orchiectomy (i.e., medical, or surgical castration).
• Laboratory tests meet minimum safety requirements:
  • Hepatic: AST ≤2.5 X institutional ULN, ALT ≤2.5 X institutional ULN, Total bilirubin ≤1.5X upper limit of normal (ULN) \[except for subjects with documented Gilbert's disease in which case total bilirubin not to exceed 10X ULN\].
  • Renal: Creatinine clearance ≥30 ml/min or serum creatinine ≤1.8 mg/dl
  • Hematological: Platelet count ≥100,000/mm\^3; Hemoglobin \>9 g/dL; ANC \>1 X10\^9/L
  • Serum potassium \>3 mEq/L