Study of Enzalutamide in Patients With Castration-resistant Prostate Cancer

Inclusion Criteria

• Participants must meet the following criteria on screening examination to be eligible to participate in the study:
• Be a male ≥ 18 years of age.
• Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate without ≥50% neuroendocrine differentiation or small cell histology.
• Participants must have progressive disease as defined by either:
• Castrate resistant disease as defined by PCWG. Participants must have a rise in PSA on two successive determinations at least one week apart and PSA levels ≥ 2 ng/ml (only the screening PSA needs to be ≥ 2 ng/ml) and testosterone levels 60%, see Appendix A).
• Participants must have normal organ and marrow function as defined below:
• WBC ≥ 3,000/mcL
• ANC ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Hemoglobin ≥ 9 g/dL
• Serum albumin ≥ 3.0 g/dL
• AST, ALT, and total bilirubin ≤ 1.5 x Institutional ULN
• Creatinine ≤ 1.5 Institutional ULN or a calculated creatinine clearance ≥ 50 mL/min using the Cockcroft Gault equation
• PTT ≤ 60, INR ≤ 1.5 Institutional ULN unless on warfarin therapy (investigator would need to determine if safe for participant to stop warfarin prior to biopsy)
• Have signed an informed consent document indicating that the subjects understands the purpose of and procedures required for the study and are willing to participate in the study.
• Be willing/able to adhere to the prohibitions and restrictions specified in this protocol.
• Written Authorization for Use and Release of Health and Research Study Information (US sites only) has been obtained.
• Able to swallow the study drug whole as a tablet.
• Participants who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator during the treatment period and for 1 week after last dose of enzalutamide.

Exclusion Criteria

• Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
• Uncontrolled illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements within 6 months of enrollment.

Clinically significant heart disease as evidenced by:

• Myocardial infarction within 6 months of enrollment.
• Uncontrolled angina within 6 months of enrollment.
• Congestive heart failure NYHA Class III or IV, or a history of congestive heart failure NYHA Class III or IV in the past, unless a screening ECHO or MUGA within 3 months results in a left ventricular ejection fraction ≥ 45%.
• Clinically significant ventricular arrhythmias.
• History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place.
• Bradycardia as indicated by a heart rate 170 mmHg or DBP > 105 mmHg on 2 consecutive measurements at screening visit.
• Thromboembolism within 6 months of enrollment.
• History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.
• History of seizure or any condition or concurrent medication that may predispose to seizure.
• 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 if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy, or 2) individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: superficial bladder cancer, basal cell or squamous cell carcinoma of the skin.
• Known brain metastasis. Participants with brain metastasis can only be included if they were treated > 4 week prior to enrollment with radiation and the effects of treatment have resolved. Subj