Zoledronate and BMS-275291 in Treating Patients With Prostate Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed (adeno)carcinoma of the prostate refractory to hormone therapy

• Metastatic bone disease, as documented by bone scan and confirmed by x-rays, CT scan or MRI scan

  • Note: Patients may also have measurable disease in the lymph nodes (retroperitoneal, pelvic or inguinal only), prostate and /or prostatic bed; measurable disease is defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm =< 21 days prior to registration
• PSA progression defined as two consecutive increases in PSA value over the previous reference value; the first increase of PSA should occur no earlier than one (1) week after the reference measurement; all patients need to demonstrate continued PSA elevation with an increasing PSA four weeks after the required cessation of their antiandrogen treatment; the required cessation period is 4 weeks for flutamide, nilutamide, and Megace-based treatment, and 8 weeks for bicalutamide-based treatment

• One of the following:

  • Continuing primary androgen suppression (LHRH agonist)
  • Orchiectomy
• WBC >= 2000/mm^3
• Absolute neutrophil count (ANC) >= 1500/mm^3
• PLT >= 100,000/mm^3
• Hgb >= 9.0 g/dL
• Total bilirubin =< institutional upper normal limits (UNL)
• AST =< 1.5 x UNL
• Serum creatinine =< 1.5 x UNL
• PSA >= 5 ng/mL
• Serum testosterone < 50 ng/dL =< 3 months prior to registration
• Estimated life expectancy of >= 6 months
• ECOG Performance Status (PS) 0, 1, or 2
• Capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent
• If sexually active, willing to use an accepted and effective method of contraception consistently for the duration of study participation

Exclusion Criteria:

• Any of the following:

  • > 2 prior chemotherapy regimen
  • > 2 non-hormonal treatments for metastatic disease (including biologics, gene therapy, angiogenesis inhibitors, etc., but excluding external radiotherapy)
  • Prior therapy with a matrix metalloproteinase inhibitor (MMPI)
  • Immunotherapy =< 4 weeks prior to study entry
  • Biologic therapy =< 4 weeks prior to study entry
  • Radiation therapy =< 4 weeks prior to study entry
  • Concomitant hormonal treatment (except LHRH)
  • Prior use of systemic radiopharmaceuticals such as samarium and strontium
  • PC-Spes =< 4 weeks prior to study entry
  • Failure to fully recover from adverse effects of prior therapies regardless of interval since last treatment
  • Other concurrent chemotherapy, immunotherapy, or radiotherapy directed at the cancer
  • Other therapy or supportive care that is considered investigational
• Known CNS metastases
• Known visceral metastases (pulmonary, liver, kidney, splenic lesions); patients with retroperitoneal, pelvic or inguinal lymph node metastases and/or disease in the prostate (or prostatic bed) will not be excluded

• Uncontrolled intercurrent illness including, but not limited to:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris, cardiac arrhythmia
  • Psychiatric illness/social situations that would limit compliance with study requirements
• HIV-positive patients receiving combination anti-retroviral therapy
• Prior malignancy except for adequately treated basal cell or squamous cell skin cancer, adequately treated noninvasive carcinomas, or other cancer from which the patient has been disease free for >= 5 years