A Randomized Study of Enzalutamide in Patients With Localized Prostate Cancer Undergoing Active Surveillance

Inclusion Criteria:

Histologically proven adenocarcinoma of the prostate diagnosed (with ≥10 core biopsy) within 6 months of screening. The biopsy that was used for this diagnosis must be submitted for central pathology review.

Prostate cancer categorized (as determined by central pathology review) as low risk is defined as T1c-T2a, PSA<10, N0, M0 (or presumed N0, M0 if CT/bone scan not done due to low risk of metastases), GS ≤ 6, ECOG status ≤2 and estimated life expectancy >5 years OR intermediate risk is defined as T2b-T2c, PSA<20, N0, M0 (or presumed N0, M0 if CT/bone scan not done), GS ≤7 (3+4 pattern only), ECOG status ≤ 2 and estimated life expectancy > 5 years. Prostate cancer categorized (as determined by central pathology review) to the very low risk category (T1c, GS ≤6, PSA <10 ng/mL, fewer than 3 prostate biopsy cores positive,

≤50% cancer in any core, PSA density <0.15 ng/mL/g) is not included.

Ability to swallow study drugs and to comply with study requirements throughout the study
Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written Informed Consent and privacy language as per national regulations must be obtained from the subject or legally authorized representative prior to any study-related procedures

Throughout study, male subject and a female partner who is of childbearing potential must use two acceptable methods of birth control (one of which must include a condom barrier method of contraception) starting at screening and continuing throughout the study period and for three months after the final study drug administration. Two acceptable methods of birth control thus include the following:

Condom (barrier method of contraception) AND
One of the following is required:

i. Established use of oral, injected or implanted hormonal methods of contraception by the female partner; ii. Placement of an intrauterine device or intrauterine system by the female partner; iii. Additional barrier method: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam / gel / film / cream / suppository by the female partner; iv. Tubal ligation in the female partner.

Must not donate sperm starting at screening throughout the study period and for 90 days after the final study drug administration.

Exclusion Criteria:

Prior radiotherapy, surgery, chemotherapy, or hormonal therapy for prostate cancer
Very low risk category (T1c, GS ≤6, PSA <10 ng/mL, fewer than 3 prostate biopsy cores positive, ≤50% cancer in any core, PSA density <0.15 ng/mL/g)
Prior transurethral resection of the prostate or prior transurethral microwave thermotherapy of the prostate
Use of oral glucocorticoids within 1 month of screening
Use of 5 alpha reductase inhibitor within 1 month of screening or total use, within the last two years prior to screening, of >3 months
Presence of metastatic disease
History of seizure or any condition that may predispose to seizures at any time in the past. History of loss of consciousness or transient ischemic attack within 12 months of screening
Absolute neutrophil count < 1,500/μL, platelet count < 100,000/μL, or hemoglobin < 6.2 mmol/L (10 g/dL) at screening
Total bilirubin >1.5 times the upper limit of normal (ULN) or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2.5 X ULN at screening
Creatinine > 177 μmol/L (> 2 mg/dL) at screening
Albumin < 30 g/L (3.0 g/dL) at screening
Major surgery within 4 weeks prior to Randomization Visit

Clinically significant cardiovascular disease including:

Myocardial infarction or uncontrolled angina within 6 months
Congestive heart failure New York Heart Association (NYHA) class 3 or 4
History of clinically significant ventricular arrhythmias
History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
Hypotension as indicated by systolic blood pressure < 86 millimeters of mercury (mm Hg) at screening
Bradycardia as indicated by a heart rate of < 45 beats per minute on the screening electrocardiogram (ECG) and on physical examination
Uncontrolled hypertension as indicated by at least 2 consecutive measurements of a resting systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at the Screening Visit
Known hypersensitivity to enzalutamide or any of its components.
Subject has received investigational therapy within 28 days or 5 half lives, whichever is longer, prior to screening