This phase II trial is studying how well eribulin mesylate (E7389; Halichondrin B Analog) works in treating patients with metastatic prostate cancer that did not respond to hormone therapy. Drugs used in chemotherapy, such as eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PRIMARY OBJECTIVES:

I. Determine the number of patients with a > 50% decrease in prostate-specific antigen (PSA) of at least 4 weeks duration in patients with hormone-refractory metastatic prostate cancer treated with E7389 (eribulin mesylate).

SECONDARY OBJECTIVES:

I. Estimate the measurable disease response in patients with measurable disease.

II. Determine the duration of PSA and measurable disease response.

III. Characterize the safety and tolerability of E7389 in these patients.

OUTLINE:

This study enrolled 3 cohorts of patients based on the number of prior chemotherapy regimens received. The 3 cohorts are chemonaive stratum, prior-taxane stratum, and two-prior-chemotherapy stratum. Patients receive eribulin mesylate intravenously (IV) over 5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years.

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate
• Progressive metastatic disease or stable metastatic disease with rising PSA
• 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
• Adequate bone marrow function
• Bilirubin =< 1.5 mg/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times upper limit of normal
• Creatinine =< 2.0 mg/dL OR creatinine clearance >= 40 mL/min
• Fertile patients must use effective contraception
• A taxane-based regimen, mitoxantrone, or other cytotoxic chemotherapy regimen allowed provided there is evidence of disease progression
• 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 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)
• 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

Exclusion Criteria:

• Active angina pectoris
• Known New York Heart Association class III-IV heart disease
• Myocardial infarction within the past 6 months
• Evidence of ventricular dysrhythmias or other unstable arrhythmia (rate-controlled atrial fibrillation is allowed if the patient is asymptomatic from a cardiac standpoint)
• Peripheral neuropathy > grade 2
• 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
• Serious concurrent medical illness or active infection that would preclude study treatment - No concurrent strong inhibitors or inducers of CYP3A4
• More than 2 prior chemotherapy regimens for hormone-refractory disease - Other concurrent investigational agents
• Other concurrent anticancer therapy, including chemotherapy, gene therapy, biologic therapy, or immunotherapy
• Concurrent palliative radiotherapy
• Concurrent estrogen, estrogen-like agents, or any other hormonal therapy
• Carcinomatous meningitis or brain metastases
• Prior strontium chloride Sr 89, samarium 153 lexidronam pentasodium, or other radioisotopes
• Concurrent therapeutic anticoagulation with warfarin (Unfractionated heparin [standard, low-dose, or adjusted dose] or low molecular weight heparin allowed