Abiraterone Acetate in Asymptomatic or Mildly Symptomatic Patients With Metastatic Castration-Resistant Prostate Cancer

This is a randomized (individuals will be assigned by chance to study treatments),
double-blind (individuals and study personnel will not know the identity of study
treatments), 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 in approximately 1,000 medically
or surgically castrated male patients with metastatic CRPC who have shown tumor progression
and are asymptomatic or mildly symptomatic. The study period will consist of screening,
treatment, and follow-up phases. Patients will receive study treatment (abiraterone acetate
or placebo) plus prednisone until radiographic progression of disease and/or unequivocal
clinical progression. Efficacy evaluations will be performed throughout the treatment period
and safety will be assessed until 30 days after the last dose of abiraterone acetate.
throughout the study. Follow-up will continue for up to 60 months (5 years) or until the
patient dies, is lost to follow-up, or withdraws informed consent. At the interim analysis of
overall survival (OS; 43% of death events), the independent data monitoring committee (IDMC)
reviewed the efficacy and safety data and concluded that all of the data pointed to a
significant advantage for patients in one arm of the study compared with the other arm
thereby unanimously recommending unblinding the study and allowing crossover from the placebo
arm to active therapy. Patients currently receiving placebo will be offered crossover therapy
to abiraterone acetate. Treatment for patients who were originally randomized to the
abiraterone acetate treatment group will not change. Patients will be discontinued from long
term follow-up at the time of the Clinical Cut-Off Date for Final Analysis (CCO-FA); however,
patients still receiving treatment with abiraterone acetate at the CCO-FA will be offered to
receive continued treatment for an additional period of up to 3 years or until disease
progression or unacceptable toxicity. For these patients, safety assessment will be performed
while continuing treatment, and for 30 days after the last dose of abiraterone acetate.

Inclusion Criteria:

- Metastatic castration-resistant prostate cancer (CRPC)

- Previous anti-androgen therapy and progression after withdrawal

- ECOG performance status of either 0 or 1

- Medical or surgical castration with testosterone less than 50 ng/dL

- Life expectancy of at least 6 months

Exclusion Criteria:

- Prior cytotoxic chemotherapy or biologic therapy for CRPC

- Prior ketoconazole for prostate cancer

- Known brain metastasis or visceral organ metastasis

- Use of opiate analgesics for cancer-related pain, including codeine and
dextropropoxyphene, currently or anytime within 4 weeks of Cycle 1 Day 1