Study of Abiraterone Acetate Without Exogenous Glucocorticoids in Men 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 one or more of the following:
• Castrate resistant disease as defined by Prostate cancer working Group (PCWG).[30] 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:

• Platelets > 50,000/microliter (mcL)
• Serum potassium ≥ 3.5 mmol/L (independent of potassium supplementation)
• Serum albumin ≥ 3.0 g/dL
• Aspartate transaminase (AST), Alanine transaminase (ALT), and total bilirubin ≤ 1.5 x Institutional Upper Limit of Normal (ULN).
• Partial thromboplastin time (PTT) ≤ 60, International Normalized Ratio (INR) ≤ 1.5 Institutional ULN unless on warfarin therapy (investigator would need to determine if safe for participant to stop warfarin prior to biopsy)
• Controlled blood pressure (systolic blood pressure < 140 and diastolic blood pressure <90) 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.
• EKG showing a normal QTc interval (QTc < 450 msec).
• Left ventricular ejection fraction ≥ 50%.
• 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.
• Willing to take AA on an empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose AA is taken.
• 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 PI during the treatment period and for 1 week after last dose of AA.

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 or would make prednisone/prednisolone (corticosteroid) use contraindicated.
• Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class III or IV heart disease or cardiac ejection fraction measurement of < 50 % at baseline.
• Thromboembolism within 6 months of Cycle 1, Day 1.
• Severe hepatic impairment (Child-Pugh Class C).
• History of pituitary or adrenal dysfunction.
• Poorly controlled diabetes.
• History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.
• Have a pre-existing condition that warrants long-term corticosteroid use.
• 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