Abiraterone Acetate Plus LHRH Agonist and Abiraterone Acetate Plus LHRH Agonist and Enzalutamide

Inclusion Criteria

• Be willing/able to adhere to the prohibitions and restrictions specified in this protocol
• Have signed an informed consent document indicating that the subjects understand the purpose of and procedures required for the study and are willing to participate in the study
• Written Authorization for Use and Release of Health and Research Study Information has been obtained.
• Male age >/=18 years.
• Histologically or cytologically confirmed adenocarcinoma of the prostate with no histological variants (such as small cell, sarcomatoid, pure ductal cancer, transitional cell carcinoma).
• Pathology review at treating academic institution or member institution (Note: if patient's prostate biopsy was not read at the treating institution, it must be reviewed at the study site to confirm eligibility).
• At least three core biopsies involved with cancer (a minimum of 6 core biopsies must be obtained at baseline). A prostate biopsy within 3 months from screening is allowed for entry requirements. Patients must have a Gleason score > 5 (total).
• At least one of the following features: a) PSA > 10 ng/ml; b) PSA velocity > 2 ng/ml/year (defined as a rise in PSA of > 2 ng/ml in the preceding 12 month period); c) Gleason score >/= 7; d) Gleason score 6 if either PSA >/= 10 ng/ml or PSA velocity >/=2 ng/ml/year
• Serum testosterone >200 ng/dL. For patients treated with 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 > 200 ng/dL.
• Urologist must agree that 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 >/= 10.0 g/dL independent of transfusion.
• Platelet count >/=100,000/µL.
• Patients should have adequate bone marrow function defined as an absolute peripheral neutrophil count (ANC) >/= 1,500.
• Creatinine clearance >/= 60 mL/min
• Serum potassium >/= 3.5 mmol/L.
• Serum albumin >/= 3.5 g/dL.
• Liver function test with serum bilirubin 7.0 at screening.
• Active or symptomatic viral hepatitis or chronic liver disease.
• History of pituitary or adrenal dysfunction.
• Clinically significant cardiovascular disease including: a) Myocardial infarction within 6 months of Screening visit; b) Uncontrolled angina within 3 months of Screening visit; c) Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within three months of the Screening visit results in a left ventricular ejection fraction that is >/= 50%; d) History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsade de pointes); e) Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on the screening Electrocardiogram (ECG) > 470 msec; f) History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place;
• (Exclusion #7 continued): g) Hypotension (systolic blood pressure /= 30% probability of recurrence within 12 months.
• History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.
• Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens, ketoconazole, or estrogens (5-alpha reductase inhibitors allowed), or LHRH agonists/antagonists (*Note: LHRH allowed if begun within 1 month of Day 1). Patients having previous or current antiandrogen treatment of greater than 4 weeks in duration prior to Cycle 1 Day 1 are eligible with appropriate washout.
• Prior systemic treatment with an azole drug within four weeks of Cycle 1 Day1