Apalutamide and Gonadotropin-Releasing Hormone Analog With or Without Abiraterone Acetate in Treating Participants With Prostate Cancer

Inclusion Criteria

• Patients must have histologically or cytologically confirmed adenocarcinoma of the prostate with no histological variants (such as small cell, sarcomatoid, pure ductal cancer, transitional cell carcinoma).
• Patients may have received one prior depot injection of LHRH agonist or LHRH antagonist (degarelix) within 30 days prior to study entry. Patients who have received any other prior hormonal therapy or any chemotherapy for prostate cancer will be excluded. (Patients who have discontinued finasteride or dutasteride or testosterone supplement for at least 2 weeks will be allowed to enroll).
• Be willing/able to adhere to the prohibitions and restrictions specified in this protocol.
• Have signed an informed consent document indicating that the subject understands the purpose of and procedures required for the study and is willing to participate in the study.
• Written authorization for use and release of health and research study information has been obtained.
• Pathology review at Monroe Dunaway (MD) Anderson (Note: if patient's prostate biopsy was not read at MD Anderson, it must be reviewed at the study site to confirm eligibility).
• Prostate biopsy. If previous biopsy has been performed within 3 months of screening, second biopsy procedure will not be required, if archival biopsies and at least one formalin fixed paraffin embedded biopsy tissue block containing tumor is available.
• The following tumor stage and Gleason scores: a) clinical >= stage T1c/T2 tumor with Gleason score >=8 b) clinical stage >= T2b tumor with Gleason score >= 7 and PSA > 10 ng/ml.
• Serum testosterone > 150 ng/dL. For patients treated up to 1 month of LHRH agonist, a testosterone measurement prior to the LHRH treatment will be used to determine eligibility, and must have been > 150 ng/dL. If no testosterone level is available from before LHRHa injection up to 30 days prior to study entry, the patient will be ineligible.
• Patient is suitable for prostatectomy.
• No evidence of metastatic disease as determined by imaging procedures.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Hemoglobin >= 9.0 g/dL independent of transfusion.
• Platelet count >= 100,000/uL.
• Absolute peripheral neutrophil count (ANC) > 1,000.
• Creatinine clearance >= 50 mL/min.
• Serum potassium >= 3.5 mmol/L.
• Serum bilirubin = = 3 g/dl.
• Able to swallow the study drug whole as a tablet.
• Patients must have normal coagulation profile and no history of substantial non-iatrogenic bleeding diathesis.
• 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.
• Willing to take abiraterone acetate on an empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose of abiraterone acetate is taken.
• Life expectancy of greater than 12 months.

Exclusion Criteria

• Patients who have had any prior chemotherapy or radiotherapy for prostate cancer.
• Patients who have had > 1 LHRH agonist or antagonist depot injection or received depot injection > 30 days before study entry.
• Patients may not be receiving any other investigational agents.
• Patients may not be receiving the concomitant administration of any systemic therapy, biologic therapy, or other agents with anti-tumor activity against prostate cancer while the patients are on study.
• Patients with known metastatic prostate cancer.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to leuprolide acetate, abiraterone acetate, prednisone or apalutamide or other agents used in the study.
• Uncontrolled intercurrent illness