RATIONALE: BMS-275291 may stop the growth of prostate cancer by stopping blood flow to the tumor and by blocking the enzymes necessary for tumor cell growth.

PURPOSE: Randomized phase II trial to study the effectiveness of BMS-275291 in treating patients who have prostate cancer that has not responded to hormone therapy.

OBJECTIVES:

• Compare the time to disease progression in patients with hormone-refractory prostate cancer treated with two different doses of BMS-275291.
• Determine the overall survival of patients treated with this drug.
• Determine the rate of response, in terms of PSA and measurable disease, in patients treated with this drug.
• Determine the qualitative and quantitative toxic effects of this drug in these patients.
• Correlate tumor response with changes in the levels of serum osteocalcin, alkaline phosphatase, procollagen I carboxy-terminal propeptide, procollagen I amino-terminal propeptide, and N-telopeptide, and with changes in the levels of urine pyridinoline and deoxypyridinoline in patients treated with this drug.

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.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

• Metastatic disease

  • Bone metastases by x-ray, bone scan, MRI, or biopsy

• Hormone-refractory disease (despite androgen deprivation and antiandrogen withdrawal if applicable) defined by at least 1 of the following criteria:

  • Progression of unidimensionally measurable disease within the past 28 days
  • Progression of evaluable but not measurable disease within the past 28 days
  • At least 2 consecutive increases in PSA taken at least 1 week apart

• Measurable or non-measurable disease

  • Soft tissue disease that has been irradiated within the past 2 months is not considered measurable disease
  • Soft tissue disease that has been irradiated 2 or more months prior to study is considered measurable disease if the lesion progressed after radiation
  • Must have at least 1 measurable lesion outside previously irradiated area to be considered measurable disease
• Must have been surgically or medically castrated
• No prior or concurrent, treated or untreated brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than upper limit of normal (ULN)
• AST and ALT no greater than 2 times ULN

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 60 mL/min

Other:

• Fertile patients must use effective contraception during and for 3 months after study
• Recovered from prior major infections
• No other significant active concurrent medical illness that would preclude study
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of any site, or other adequately treated stage I or II cancer that is in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent biological response modifiers

Chemotherapy:

• No more than 1 prior chemotherapy regimen
• At least 3 weeks since prior chemotherapy and recovered
• No concurrent chemotherapy

Endocrine therapy:

• See Disease Characteristics
• At least 4 weeks since prior flutamide or ketoconazole
• At least 6 weeks since prior bicalutamide or nilutamide
• Must continue any luteinizing hormone-releasing hormone (LHRH) agonist therapy (e.g., leuprolide or goserelin) started prior to study
• No concurrent corticosteroid or hormonal therapy (except LHRH agonist therapy)

Radiotherapy:

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy and recovered
• At least 3 months since prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium and recovered
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics
• Recovered from any prior surgical procedures

Other:

• No concurrent bisphosphonates unless therapy began prior to study
• No concurrent unconventional therapy for malignancy (e.g., St. John's Wort, PC-SPES, or other herbal remedies)