A Phase II Study of Increased-Dose Abiraterone Acetate in Patients With Castration Resistant Prostate Cancer

Inclusion Criteria: * 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 has been obtained * Male aged 18 years and above * Able to swallow the study drug whole as a tablet * Willing to take abiraterone acetate on an empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose of abiraterone acetate is taken * Patients 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 and sponsor during the study and for 1 week after last study drug administration. * Have a baseline serum potassium of ≥ 3.5 milliequivalents per litre (mEq/L) * Have aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin levels \< 1.5 x upper limit of normal (ULN) * Have a serum albumin of ≥ 3.0 g/dL * Total bilirubin ≤ 1.5 x ULN (In patients with known Gilbert Syndrome, a total bilirubin ≤ 3.0 x ULN, with direct bilirubin ≤ 1.5 x ULN is acceptable) * Have a platelet count of ≥ 100,000/μL * Have an absolute neutrophil count of \> 1500 cell/mm3 * Have a calculated creatinine clearance ≥ 60 mL/min * Have a hemoglobin of ≥ 9.0 g/dL * Have histologically confirmed adenocarcinoma of the prostate. * No prior therapy with chemotherapy for metastatic prostate cancer. * Have metastatic disease based on a positive bone scan or objective imaging on CT scan. * Have ongoing gonadal androgen deprivation therapy with Luteinizing hormone-releasing hormone (LHRH) analogues or orchiectomy. Patients who have not had an orchiectomy must be maintained on effective LHRH analogue therapy for the duration of the trial. * Testosterone \< 50 ng/dL. * Progressive disease after androgen deprivation: PSA evidence for progressive prostate cancer consists of a PSA level of at least 2 ng/ml which has risen on at least 2 successive occasions, at least 2 weeks apart. If the confirmatory PSA value is less than the screening PSA value, then an additional test for rising PSA will be required to document progression. * Antiandrogen Withdrawal (AAWD): Patients who are receiving an antiandrogen as part of primary androgen ablation must demonstrate disease progression following discontinuation of antiandrogen. * Disease progression after antiandrogen withdrawal is defined as 2 consecutive rising PSA values, obtained at least 2 weeks apart, or documented osseous or soft tissue progression. * For patients receiving flutamide, at least one of the PSA values must be obtained 4 weeks or more after flutamide discontinuation. * For patients receiving bicalutamide or nilutamide, at least one of the PSA values must be obtained 6 weeks or more after antiandrogen discontinuation. * No antiandrogen withdrawal response is expected in patients in whom antiandrogen therapy did NOT result in a decline in PSA or in those patients in whom the response to antiandrogens was \< 3 months. Therefore, it is not necessary to wait for AAWD in patients without PSA decline on an anti-androgen or in those in whom a PSA response lasted \< 3 months. * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 * Life expectancy of ≥ 12 weeks. Exclusion Criteria: * Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated * Known brain metastasis * Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg) Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment * Active or symptomatic viral hepatitis or chronic liver disease * History of pituitary or adrenal dysfunction * 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 II-IV heart disease or cardiac ejection fraction measurement of \< 50 % at baseline * Atrial Fibrillation, or other cardiac arrhythmia requiring medical therapy * Administration of an investigational therapeutic within 30 days of screening * Have poorly controlled diabetes * Have a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents * Have a pre-existing condition that warrants long-term corticosteroid use in excess of study dose * Have known allergies, hypersensitivity, or intolerance to abiraterone acetate or prednisone or their excipients * Any condition which, in the opinion of the investigator, would preclude participation in this trial. * Pure small cell carcinoma of the prostate or any mixed histology cancer of the prostate (eg: neuroendocrine) which contains \< 50% adenocarcinoma. * Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace), finasteride (Proscar), dutasteride (Avodart) any herbal product known to decrease PSA levels (e.g., Saw Palmetto and PC-SPES), or any systemic corticosteroid within 4 weeks prior to first dose of study drug. * Prior therapy with Abiraterone Acetate or other CYP17 inhibitor(s) including TAK-700 or TOK-001, or investigational agent(s) targeting the androgen receptor for metastatic prostate cancer. * Prior therapy with ketoconazole for \> 2 weeks for prostate cancer. * Therapy with supplements or complementary medicines/botanicals within 4 weeks of first dose of study drug, except for any combination of the following: * Conventional multivitamin supplements * Selenium * Lycopene * Soy supplements * Prior radiation therapy completed \< 4 weeks prior to enrollment * Prior chemotherapy for castration resistant prostate cancer. Patients who have received chemotherapy for early stage prostate cancer (e.g. as part of a neoadjuvant or adjuvant trial) or for other malignancies are eligible provided that \>1 year has passed since the administration of the last chemotherapy dose. * Any "currently active" second malignancy, other than non-melanoma skin cancer. Patients are not considered to have a "currently active" malignancy, if they have completed therapy and are considered by their physician to be at least less than 30% risk of relapse over next year. * Active psychiatric illnesses/social situations that would limit compliance with protocol requirements. * Patients in whom urgent chemotherapy, in the opinion of the treating physician, is indicated should not be enrolled in this study.