Enzalutamide and Leuprolide Acetate after Radiation Therapy in Treating Patients with High-Risk Prostate Cancer

Inclusion Criteria

• Histologically confirmed diagnosis of adenocarcinoma of the prostate within 25 weeks prior to registration at very high risk of recurrence as determined by 2 or more of the following combinations: * cT3a/b * PSA >= 20 * Gleason score 8-10 * >= 33% core involvement * OR any patient with pelvic lymph node involvement >= 1 cm as determined by pelvic computed tomography (CT) or magnetic resonance imaging (MRI) imaging will meet eligibility criteria for enrollment
• Standard staging exams for patients with high-risk prostate cancer including bone scan or sodium fluoride (NaF) positron emission tomography (PET)/CT scan, and pelvic and prostate MRI
• No distant metastases (M0) on bone scan or NaF PET/CT within 14 weeks prior to registration; equivocal bone scan findings are allowed if the physician determines that distant metastases are unlikely based on clinical judgment
• Zubrod performance status 0-2 within 14 weeks prior to enrollment
• Obtained within 14 weeks prior to registration on study: absolute neutrophil count (ANC) >= 1,800 cells/mm^3
• Obtained within 14 weeks prior to registration on study: platelets >= 100,000 cells/mm^3
• Obtained within 14 weeks prior to registration on study: hemoglobin >= 8.0 g/dl (the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
• Obtained within 14 weeks prior to registration on study: serum creatinine < 2.0 mg/dl and creatinine clearance > 40 mL/min
• Obtained within 14 weeks prior to registration on study: bilirubin < 1.5 x upper limit of normal (ULN)
• Obtained within 14 weeks prior to registration on study: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2 x ULN
• Patients, even if surgically sterilized (i.e., status post vasectomy), who: * Agree to practice effective barrier contraception during the entire study treatment period and for 4 months (120 days) after the last dose of study drug, or * Agree to completely abstain from intercourse
• Patient must be able to provide study-specific informed consent prior to study entry

Exclusion Criteria

• Definite evidence of metastatic disease
• Prior radical prostatectomy or bilateral orchiectomy for any reason
• Prior invasive malignancy (except non-melanoma skin cancer) unless disease- free or not requiring systemic therapy for a minimum of 3 years
• Prior systemic chemotherapy for prostate cancer (note that prior chemotherapy for a different cancer is allowed)
• Prior radiotherapy, including brachytherapy, to the region of the prostate that would result in overlap of radiation therapy fields
• Previous hormonal therapy such as luteinizing hormone releasing hormone (LHRH) agonists (e.g. goserelin, leuprolide), anti-androgens (e.g. flutamide, bicalutamide), estrogens (e.g. diethylstilbestrol [DES]), or surgical castration (orchiectomy)
• Known hypersensitivity to enzalutamide or related compounds
• History of adrenal insufficiency
• Patients who are sexually active and not willing/able to use medically acceptable forms of contraception
• Prior allergic reaction to the drugs involved in this protocol
• Cushing’s syndrome
• Severe chronic renal disease (serum creatinine > 2.0 mg/dl and confirmed by creatinine clearance < 40 mL/minute)
• Chronic liver disease (bilirubin > 1.5 x ULN, ALT or AST > 2 x ULN)
• Active/uncontrolled viral hepatitis
• Chronic treatment with glucocorticoids within one year
• History of seizure including febrile seizure or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization); also, current or prior treatment with antiepileptic medications for the treatment of seizures or history of loss of consciousness or transient ischemic attack within 12 months prior to randomization
• Clinically significant cardiovascular disease including: * Myocardial infarction within 6 months prior to screening * Uncontrolled angina within 3 months prior to screening * 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, unless a screening echocardiogram or multi-gated acquisition (MUGA) scan performed within 3 months results in a left ventricular ejection fraction that is >= 45% * History of clinically significant ventricular arrhythmias (e.g. ventricular tachycardia, ventricular fibrillation, torsades de pointes) * History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place * Uncontrolled hypertension as indicated by a resting systolic blood pressure > 170 mm Hg or diastolic blood pressure > 105 mm Hg at screening; patients with initially elevated systolic blood pressure > 170 mm Hg or diastolic blood pressure > 105 mm Hg are eligible if they undergo medical management and are re-screened