A Study of Abiraterone Acetate Plus Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Docetaxel-Based Chemotherapy

This is a randomized (the treatment group is assigned by chance), double-blind (neither physician nor patient knows the treatment that the patient receives) placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial)-controlled study with a randomization allocation ratio of 2:1 between the abiraterone acetate group (abiraterone acetate plus prednisone) and the placebo group (placebo plus prednisone). Approximately 200 (133 in the abiraterone acetate group and 67 in the placebo group) medically or surgically castrated male patients with mCRPC who have failed docetaxel-based chemotherapy will be enrolled in this study for up to 27 months. The study protocol includes the following phases: screening (within 28 days prior to randomization on Cycle 1 Day 1), double-blind treatment (28-day cycles until protocol-defined disease progression or unacceptable toxicity), and survival follow-up (up to Month 60). During the follow-up phase, patients with disease progression will be provided open-label (identity of assigned study drug will be known) extension treatment with abiraterone acetate. In the event of a positive study result at the time of the final analysis, participants in the placebo group who have not shown progressive disease in the double-blind treatment Phase of the study will be enrolled in an open-label extension treatment with abiraterone acetate treatment based on the participant's choice and treating physician's endorsement if they meet the criteria for subsequent abiraterone acetate. Abiraterone acetate 1000 mg tablets or placebo will be taken orally (by mouth) once daily plus prednisone 5 mg tablet orally twice daily. Efficacy and safety will be monitored throughout the study.

Inclusion criteria

• Histologically or cytologically confirmed adenocarcinoma of the prostate except neuroendocrine carcinoma including small cell carcinoma
• Disease progressed on or after prior docetaxel-containing chemotherapy
• Prior 1 or 2 cytotoxic chemotherapy regimens for metastatic castration-resistant prostate cancer, at least 1 of which contains docetaxel
• Documented prostate cancer progression as documented by prostate specific antigen progression according to Prostate Specific Antigen Working Group criteria or radiographic progression in soft tissue or bone
• Surgically or medically castrated, with serum testosterone level <50 ng/dL (1.7 nmol/L)
• Eastern Cooperative Oncology Group performance status score of <=2
• Protocol-defined laboratory values
• Agrees to protocol-defined use of effective contraception

Exclusion criteria

• Active infection or other medical condition that would make prednisone (corticosteroid) use contraindicated
• Any chronic medical condition requiring a higher dose of corticosteroid than 5 mg prednisone twice daily
• Pathological finding consistent with neuroendocrine carcinoma of prostate including small cell carcinoma
• 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 therapy)
• Active or symptomatic viral hepatitis or chronic liver disease, have a known infection with human immunodeficiency virus and/or hepatitis B virus or hepatitis C virus
• 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 Class III or IV heart disease or cardiac ejection fraction measurement of <50% at baseline
• Atrial fibrillation, or other cardiac arrhythmia requiring therapy
• Other malignancy within past 3 years (except basal or nonmetastatic squamous cell carcinoma of the skin)
• Known brain metastasis
• Prior therapy with abiraterone acetate or other CYP17 inhibitor(s), or investigational agent(s) targeting the androgen receptor for metastatic prostate cancer
• Prior therapy with ketoconazole for prostate cancer
• Surgery or local prostatic intervention within 30 days of the first dose
• Radiotherapy, chemotherapy, or immunotherapy within 30 days, or single fraction of palliative radiotherapy within 14 days of administration of Cycle 1 Day 1
• Any acute toxicities due to prior chemotherapy and/or radiotherapy that have not resolved to a National Cancer Institute-Common Terminology Criteria for Adverse Events grade of <=1 (chemotherapy induced alopecia and grade 2 peripheral neuropathy is allowed)
• Current enrollment in an investigational drug or device study or participation in such a study within 30 days of Cycle 1 Day 1
• Anti-androgen treatment must not be given within 4 weeks (flutamide) or 6 weeks (bicalutamide or nilutamide) prior to Cycle 1 Day 1
• Prior systemic treatment with an azole drug (eg, fluconazole, itraconazole) within 4 weeks prior to Cycle 1 Day 1
• Has known allergies, hypersensitivity, or intolerance to abiraterone acetate or its excipients
• Has contraindications to the use of prednisone per local prescribing information
• Has any condition that, in the opinion of the investigator, would make participation not be in the best interest (eg, compromise the well-being) of the patient or that could prevent, limit, or confound the protocol-specified assessments