BMS-275291 in Treating Patients With Prostate Cancer That Has Not Responded to Hormone Therapy

PRIMARY OBJECTIVES: I. To assess the time to disease progression in patients with hormone-refractory prostate cancer treated with two different doses of BMS-275291. SECONDARY OBJECTIVES: I. To assess the overall survival of patients with hormone-refractory prostate cancer treated with two different doses of BMS-275291. II. To assess the rate of response to BMS-275291, using both PSA and measurable disease. III. To evaluate the qualitative and quantitative toxic effects of this agent in this patient population. IV. To investigate the correlation of tumor response with changes in the levels of serum osteocalcin, alkaline phosphatase, procollagen I carboxy-terminal propeptide (PICP), procollagen I amino-terminal propeptide (PINP), and N-telopeptide; and the correlation of tumor response with changes in the levels of urine pyridinoline and deoxypyridinoline. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to Gleason score (2-4 vs 5-7 vs 8-10), PSA level (less than 10 ng/mL vs 10-50 ng/mL vs 51-100 ng/mL vs more than 100 ng/mL), and concurrent bisphosphonate therapy (yes vs no). Patients are randomized to one of two treatment arms. ARM I: Patients receive oral BMS-275291 once daily on days 1-28. ARM II: Patients receive oral BMS-275291 twice daily on days 1-28. In both arms, treatment repeats every 28 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 additional courses beyond CR. Patients are followed until death. PROJECTED ACCRUAL: A total of 24-68 patients (12-34 per treatment arm) will be accrued for this study within 5-14 months.