A Phase II Trial of E7389 (Halichondrin B Analog), in Patients With Metastatic Hormone Refractory Prostate Cancer

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the prostate

- Progressive (i.e., new lesions on bone scan or new/enlarging lesions on CT scan) or
stable metastatic disease*

- Patients with bone metastases only (i.e., lacking soft tissue disease) must have a
prostate-specific antigen (PSA) level >= 5 ng/mL within the past 1 week

- Patients with soft tissue metastases and/or visceral disease must have either
measurable disease OR a PSA level >= 5 ng/mL within the past 1 week

- Patients with stable metastases must have a rising PSA level within the past 4 weeks

- Two consecutive rises in PSA, each measurement taken >= 1 week apart

- [Note: *Radiologic evidence of hydronephrosis alone is not considered evidence of
metastatic disease]

- Meets 1 of the following criteria:

- Never received prior chemotherapy/cytotoxic therapy

- Received prior taxane-based regimen

- Received 2 prior cytotoxic chemotherapy regimens including, but not limited to,
prior taxane and anthracyclines

- Previously treated with bilateral orchiectomy or other primary hormonal therapy with
evidence of treatment failure

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

- Patients who did not have an orchiectomy must have a testosterone level < 50 ng/dL to
confirm androgen suppression within the past 4 weeks

- ECOG performance status 0-2

- Granulocyte count >= 1,500/mm^3

- Platelet count >= 100,000/mm^3

- Bilirubin =< 1.5 mg/dL

- AST and ALT =< 2.5 times upper limit of normal

- Creatinine =< 2.0 mg/dL OR creatinine clearance >= 40 mL/min

- No active angina pectoris

- No known New York Heart Association class III-IV heart disease

- No myocardial infarction within the past 6 months

- No evidence of ventricular dysrhythmias or other unstable arrhythmia

- Rate-controlled atrial fibrillation is allowed if the patient is asymptomatic from a
cardiac standpoint

- No peripheral neuropathy > grade 2

- No other prior malignancy (excluding nonmelanomatous skin cancer treated with
curative intent) unless the malignancy was treated with curative intent and the
patient has been disease free for >= 5 years

- No serious concurrent medical illness or active infection that would preclude study
treatment

- Fertile patients must use effective contraception

- No more than 2 prior chemotherapy regimens for hormone-refractory disease

- A taxane-based regimen, mitoxantrone, or other cytotoxic chemotherapy regimen allowed
provided there is evidence of disease progression

- Treatment with estramustine is not considered a separate cytotoxic regimen

- At least 4 weeks since prior chemotherapy or radiotherapy

- At least 4 weeks since prior flutamide (6 weeks for bicalutamide or nilutamide) and
there is continued evidence of disease progression

- Disease progression after antiandrogen withdrawal must be confirmed by rising PSA
after the required 4-6 week washout period (e.g., PSA level higher than the last PSA
obtained while on antiandrogen therapy)

- More than 4 weeks since prior and no concurrent estrogen, estrogen-like agents (e.g.,
PC-SPES, saw palmetto, or other herbal products that may contain phytoestrogens), or
any other hormonal therapy (including megestrol, finasteride, ketoconazole, or
systemic corticosteroids)

- No prior strontium chloride Sr 89, samarium 153 lexidronam pentasodium, or other
radioisotopes

- No concurrent therapeutic anticoagulation with warfarin

- Unfractionated heparin (standard, low-dose, or adjusted dose) or low molecular weight
heparin allowed

- Concurrent bisphosphonates (e.g., pamidronate sodium or zoledronate) allowed provided
the patient has been receiving the bisphosphonate for >= 4 weeks and there is
evidence of disease progression

- No concurrent strong inhibitors or inducers of CYP3A4

- No other concurrent investigational agents

- No other concurrent anticancer therapy, including chemotherapy, gene therapy,
biologic therapy, or immunotherapy

- No concurrent palliative radiotherapy

- No known carcinomatous meningitis or brain metastases