This study will examine whether the new investigational drug EPO906, given by intravenous infusion (IV directly into the vein), is effective in shrinking tumors and preventing the growth of cells that cause melanoma.

Inclusion Criteria

The following patients may be eligible for this study:

• Patients with advanced metastatic melanoma defined as poor prognosis Stage III melanoma and Stage IV disease, which has been histologically or cytologically confirmed with at least one measurable lesion not including bone metastases (if previous radiation treatment, the target lesion must have demonstrated progression since the radiation)
• Patients with poor prognosis Stage III melanoma must have locally advanced unresectable disease that is measurable (repeat histological or cytological confirmation is not necessary at the time of study entry if previous results are available and there is no question in the investigator's opinion as to the diagnosis)
• Must have a life expectancy of greater than three (3) months
• Prior immunotherapy with interferon alpha in the adjuvant setting is permitted, but must have been completed > 4 weeks prior to treatment
• Prior vaccine therapy is permitted, but must have been completed > 4 weeks prior to treatment
• Patient has no major impairment of hematological function (red blood cell transfusions and repeat evaluations for study entry are allowed).

Exclusion Criteria

The following patients are not eligible for this study:

• Patients with choroidal ocular melanoma
• Patients with symptomatic CNS metastases or leptomeningeal involvement
• Patients with renal or hepatic dysfunction
• Patients with any peripheral neuropathy or unresolved diarrhea greater than Grade 1
• Patients with severe cardiac insufficiency
• Patients taking Coumadin or other warfarin-containing agents with the exception of low dose Coumadin (1 mg or less) for the maintenance of in-dwelling lines or ports
• Patients who have received any investigational compound or anti-melanoma vaccine within the past 28 days or those who are planning to receive other investigational drugs while participating in the study
• Patients who had received radiotherapy within the last 4 weeks to a site which will be the reference for disease assessment (however, new or progressive lesions in the previously irradiated fields of these patients may be used for disease assessment and patients must have recovered from the side effects of radiotherapy)
• Patients receiving chemotherapy within the last four weeks
• History of another malignancy within 5 years prior to study entry except curatively treated non-melanoma skin cancer or cervical cancer in situ
• Patients with active or suspected acute or chronic uncontrolled infection including abcesses or fistulae
• HIV+ patients
• Pregnant or lactating females.