Phase II Study of a Weekly Schedule of BMS-247550 for Patients With Hormone Refractory Prostate Cancer

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the prostate

- Evidence of progressive metastatic disease OR metastatic disease and rising PSA
within 4 weeks prior to registration

- Patients with bone metastases only (i.e., lacking soft tissue disease) must have
a PSA level > 10 ng/mL within a week of registration

- Patients with soft tissue metastasis and/or visceral disease must have
measurable disease OR a PSA level > 10 ng/mL within a week prior to registration

- Patients with stable metastatic disease and rising PSA must show 2 consecutive
rises in PSA measurements taken at least 2 weeks apart; most recent PSA level
must be obtained within 4 weeks of registration

- Failed prior bilateral orchiectomy or other primary hormonal therapy

- Patients who have not undergone bilateral orchiectomy must continue on
luteinizing hormone-releasing hormone (LHRH) agonist therapy (e.g., leuprolide
or goserelin) or LHRH antagonist (e.g., abarelix) during study treatment

- Patients without an orchiectomy must have a serum testosterone level < 50 ng/dL
within 4 weeks of registration to confirm androgen suppression

- No carcinomatous meningitis or brain metastases

- At least 4 weeks since prior flutamide AND continued evidence of progressive disease

- At least 6 weeks since prior bicalutamide or nilutamide AND continued evidence of
progressive disease

- Depending on the strata, no more than 2 prior cytotoxic chemotherapy regimens for
hormone-refractory disease with a taxane-based regimen, mitoxantrone, or another
cytotoxic chemotherapy regimen provided there is evidence of progressive disease

- Up to 1 prior experimental (non-cytotoxic) therapy AND evidence of progressive
disease

- Concurrent bisphosphonates (e.g., pamidronate or zoledronate) allowed provided
treatment was initiated at least 4 weeks ago and there is evidence of progressive
disease

- At least 4 weeks since prior estrogen or estrogen-like agents, or other hormonal
therapy AND disease progression needs to be confirmed by a rising PSA after the
required 4-week washout period

- Adequate bone marrow function

- Serum glutamic-pyruvic transaminase (SGPT) < 2 times the institutional upper limit of
normal

- Bilirubin < 1.5 mg/dL

- Creatinine < 1.5 mg/dL OR a calculated creatinine clearance ≥ 50 mL/min

- Normal international normalized ratio (INR)

- Patients must have electrocardiography (ECG) within 4 weeks of registration

- Patients with a history of prior malignancy are eligible provided they have been
treated with curative intent and free of disease for > 5 years (excluding
non-melanomatous skin cancers treated with curative intent)

- Fertile patients must use effective contraception

- All sites of disease must have been evaluated within 4 weeks of registration

- Age 18 or older

- ECOG performance status (PS) of 0-2

Exclusion Criteria:

- Prior radiotherapy < 4 weeks prior to registration

- Prior Strontium 89, Samarium 153, or other radioisotope

- Concurrent estrogen or estrogen-like agents or any other hormonal therapy

- Active angina pectoris

- New York Heart Association class III-IV heart disease

- Myocardial infarction within 6 months prior to registration

- Evidence of ventricular dysrhythmias or unstable arrhythmia

- Carcinomatous meningitis or brain metastases.

- Peripheral neuropathy > grade 1

- Serious medical illness or active infection that would preclude study participation

- Concurrent investigational agents