Open-Label Study of TPI 287 for Patients With Metastatic Melanoma

Inclusion Criteria:

1. Patients with histologically proven melanoma with metastasis that is unresectable Stage III or Stage IV. This will include bulky stage III and M1-3.
2. Patients must have shown unequivocal evidence for tumor recurrence or progression and should have at least one indicator lesion that can be measured in one dimension as \>/= 20mm with conventional techniques (CT, MRI, and X-ray) or \>/= 10mm with spiral CT scan.
3. Patients with melanoma with documented metastases to the brain are eligible: a. Must be asymptomatic with stable disease for at least 2 months as determined by CT or MRI of the brain at the time of evaluation no measurable changes. b. May have had prior therapy for brain metastasis such as whole brain irradiation, stereotactic gamma ray therapy or resection of brain metastases.
4. Patients may have had up to two prior cytotoxic chemotherapy regimens for their systemic disease (immunological or targeted therapy e.g. vaccine, IL-2, B-RAF inhibitors, will not be considered prior cytotoxic chemotherapy)
5. All patients must sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of this hospital.
6. Patients must have a Eastern Cooperative Oncology Group (ECOG) status of \</= 2.
7. Patients must have recovered from the toxic effects of prior therapy (baseline grade), at least 3 weeks after the last dose was administered. Any questions about whether patients fulfill this criteria should be directed to the Study Chair.
8. Patients must have adequate bone marrow function (Absolute neutrophil count (ANC)\>/= 1,500/mm\^3 and platelet count of \>/= 100,000/mm\^3), adequate liver function \[aspartate aminotransferase (AST or SGOT) or alanine aminotransferase (ALT or SGPT) \</= 2.5 times normal for patients without liver metastasis and ALT (SGPT) and AST (SGOT) \</= 5, times normal for patients with liver metastasis\], serum bilirubin \</= 2 mg/dl), and adequate renal function (BUN and creatinine \>/= 1.5 times institutional normal) prior to starting therapy
9. As TPI 287 may interfere with Coumadin dosing, patients who are taking TPI 287 will require monitoring of their Prothrombin Time (PT), Partial thromboplastin time (PTT) and International Normalized Ratio (INR)
10. Females of childbearing potential (non childbearing is defined as greater than one year post-menopausal or surgically sterilized) must use acceptable contraceptive methods (abstinence, intrauterine device, oral contraceptive or double barrier device), and must have a negative serum or urine pregnancy test within 7 days prior to beginning treatment on this trial. Sexually active men must also use acceptable contraceptive methods for the duration of time on study.
11. Patient should be 15 years of age or older

Exclusion Criteria:

1. 1\. Patients with brain metastases not stable for 2 months.
2. Patients taking primidone, carbamazepine, phenobarbital or phenytoin anticonvulsants (Enzyme-Inducing Anti-Epileptic Drugs - EIAED). Patients changing from these anticonvulsants to others that are allowed must be off the drugs listed above for at least 1 week before start of treatment.
3. Patients with \> Grade 2 neuropathy
4. Patients with uncontrolled high blood pressure (systolic BP \> 140 for patients \< 50 years old and \>160 for patients \> 50 and/or diastolic BP\>90 for patients\< 50 year old and \>99 for patients over 50) unstable angina, symptomatic congestive heart failure, clinical history of myocardial infarction within the previous six months, or serious uncontrolled cardiac arrhythmia as determined by the principal investigator.
5. Because of the concerns for the potential interaction of TPI 287 and medications taken by patients who are HIV positive or have AIDS related diseases, patients who are HIV positive are not eligible for entry into this study. Only patients with suspected HIV will be tested and if positive, will be ineligible.
6. Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix) are ineligible unless in complete remission and off of all therapy for that disease for a minimum of 3 years.
7. Patients with: a. Active infection associated with fever lasting more than 24 hours requiring antibiotics b. Disease that will obscure toxicity or dangerously alter drug metabolism c. Serious intercurrent medical illness The Principal investigator or his designee will make the final decision regarding eligibility for enrollment.
8. Female patients who are pregnant or breastfeeding
9. Patients younger than 15 years of age