A Phase II, Open-Label, Randomized Trial of Zoledronic Acid (Zometa™) and BMS-275291 (NSC#713763) in Patients With Hormone Refractory 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