Enzalutamide and Leuprolide Acetate with or without Abiraterone Acetate and Prednisone before Surgery in Treating Patients with Intermediate or High Risk Prostate Cancer Undergoing Prostatectomy

Inclusion Criteria

• Histologically confirmed adenocarcinoma of the prostate without histological variants (including overt neuroendocrine differentiation, small cell neuroendocrine carcinoma features, sarcomatoid features, pure ductal adenocarcinoma, squamous or transitional cell carcinoma)
• Must have tissue available from the pre-treatment diagnostic biopsy (tissue blocks if possible; if not possible, 10 unstained slides from each positive core sample for a total of 30 slides whenever possible)
• Must have 3 core biopsies involved with cancer (a minimum of 6 core biopsies must be obtained); prostate biopsy must be within seven months from screening; this includes prostate biopsy from men previously followed by active surveillance; less than 3 core biopsies is allowed if the patient has > 1 cm or T3 disease on magnetic resonance imaging (MRI)
• Participants must have the following features: * Intermediate-risk disease defined as Gleason 4+3 = 7 disease OR * High-risk disease defined as Gleason 8-10 OR PSA > 20 ng/mL OR T3 disease (by prostate MRI)
• No evidence of metastatic or nodal disease as determined by radionuclide bone scans computed tomography (CT)/MRI; non-pathological lymph nodes must be less than 20 mm in the short (transverse) axis
• Participants must be candidates for RP and considered surgically resectable by urologic evaluation
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
• Diabetics on insulin or antihyperglycemics must be on a stable dose (i.e., no titrations within the last 2 weeks) at the time of study entry
• White blood cell (WBC) >= 3,000/mcL
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Platelets >= 100,000/mcL
• Serum potassium >= 3.5 mmol/L
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 1.5 x institutional upper limit of normal (ULN)
• Total bilirubin =< 1.5 x institutional ULN
• Calculated creatinine clearance >= 60 mL/min
• Partial thromboplastin time (PTT) =< 60, international normalized ratio (INR) =< 1.5 x institutional ULN unless on warfarin therapy (investigator would need to determine if safe for participant to stop warfarin prior to biopsy and warfarin therapy)
• Controlled blood pressure defined as a systolic blood pressure =< 140 mmHg and diastolic blood pressure =< 90 mmHg on no more than three anti-hypertensive agents; drug formulations containing two or more anti-hypertensive agents will be counted based on the number of active agents in each formulation

Exclusion Criteria

• Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens (including first-generation antiandrogens, enzalutamide, ARN-509 and others), cytochrome P450, family 17 (CYP17) inhibitors (including abiraterone, TAK-700, galeterone, ketoconazole, and others), estrogens, luteinizing hormone-releasing hormone (LHRH) agonist/antagonists; topical ketoconazole and other topical antifungal agents are allowed; prior therapy with 5alpha-reductase inhibitors is allowed; LHRH therapy allowed if begun within 4 weeks of day 1 * Prior androgens are allowed if the patient had a testosterone within the normal range prior to starting androgens and the androgens have been stopped for at least 7 days
• Prior chemotherapy, radiation therapy, or immunotherapy for prostate cancer
• Prior systemic treatment with an azole drug within four weeks of screening visit
• Hypogonadism or severe androgen deficiency as defined by screening serum testosterone < 200 ng/dL
• Clinically significant cardiovascular disease including: * Acute coronary syndrome within 6 months of screening visit * Hypotension defined as a systolic blood pressure < 86 mmHg * Bradycardia defined as a heart rate of < 50 beats per minute, unless pharmaceutically induced and thus reversible (i.e. beta blockers) * Uncontrolled angina (requiring escalating doses of nitrates) within 3 months of screening visit * Congestive heart failure New York Heart Association (NYHA) class III or IV or subjects with a history of congestive heart failure NYHA class III or IV, unless screening echocardiogram (ECHO) results in left ventricular ejection fraction that >= 45% * History of clinically significant ventricular arrhythmias (e.g. ventricular tachycardia, ventricular fibrillation, torsades de pointes) * Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on screening electrocardiogram (EKG) > 470 msec * History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
• History of seizure or any condition or concurrent medication that may predispose to seizure
• Diabetics on a stable dose of insulin or antihyperglycemic regimen are allowed if they have had no prior seizures and no history of loss of consciousness due to hypoglycemia
• Thromboembolism within 6 months of screening visit
• Severe hepatic impairment (Child-Pugh class C)
• Active or symptomatic viral hepatitis or chronic liver disease
• History of pituitary or adrenal dysfunction
• Gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug
• Pre-existing condition that warrants long-term corticosteroid use; physiologic replacement is not permitted
• Concomitant use of medications that may alter pharmacokinetics of abiraterone (abiraterone acetate) or enzalutamide
• Individuals with a history of a different malignancy are ineligible except for the following circumstances: 1) individuals with a history of other malignancies are eligible as long as there is no evidence of metastases and life expectancy deemed > 2 years
• Major surgery or radiation therapy within 30 days of screening visit