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

• Overall Survival [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
• Radiographic progression-free survival [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]

• Time to opiate use for cancer pain [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
• Time to initiation of cytotoxic chemotherapy [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
• Time to deterioration in Eastern Cooperative Oncology Group performance score by >=1 point [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
• Time to prostate-specific antigen progression based on Prostate Cancer Working Group 2 criteria [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
• Number of participants affected by an adverse event [ Time Frame: Up to 30 days after the last dose of study medication ] [ Designated as safety issue: Yes ]
• Mean plasma concentrations of abiraterone [ Time Frame: Up to Cycle 5, Day 1 ] [ Designated as safety issue: No ]
• Maximum plasma concentration of abiraterone [ Time Frame: Up to Cycle 5, Day 1 ] [ Designated as safety issue: No ]
• Time to reach the maximum plasma concentration of abiraterone [ Time Frame: Up to Cycle 5, Day 1 ] [ Designated as safety issue: No ]
• Area under the plasma concentration-time curve from time 0 to time the last quantifiable concentration of abiraterone [ Time Frame: Up to Cycle 5, Day 1 ] [ Designated as safety issue: No ]
• Area under the plasma concentration-time curve from time 0 to infinite time of abiraterone [ Time Frame: Up to Cycle 5, Day 1 ] [ Designated as safety issue: No ]
• Elimination half-life [ Time Frame: Up to Cycle 5, Day 1 ] [ Designated as safety issue: No ]

This is a phase 3 study to compare the clinical benefit of abiraterone acetate plus prednisone with placebo plus prednisone in patients with asymptomatic or mildly symptomatic patients with metastatic castration-resistant prostate cancer (CRPC).

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 and safety will be assessed throughout the study. Follow-up will continue for 60 months (5 years) or until 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.

• Drug: Abiraterone acetate
  Type=exact number, unit=mg, number=1000, form=tablet, route=oral use. Tablets are taken once daily.
• Drug: Placebo
  Form=tablet, route=oral use. Tablets are taken once daily.
• Drug: Prednisone
  Type=exact number, unit=mg, number=5, form=tablet, route=oral use. Tablets are taken twice daily.

• Placebo Comparator: Placebo + prednisone
  Placebo plus prednisone
  Interventions:

  • Drug: Placebo
  • Drug: Prednisone
• Experimental: Abiraterone + prednisone
  Abiraterone acetate plus prednisone
  Interventions:

  • Drug: Abiraterone acetate
  • Drug: Prednisone

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