Vanderbilt-Ingram Cancer Center

Patients are being asked to take part in this research study because they have a type of melanoma called acral/lentiginous which has spread beyond the local area. The purpose of this study is to see if SU011248 (the study drug) works in keeping your cancer from getting worse. The study drug works by blocking signals to the cancer cells that allow them to multiply and spread. This research study is a Phase II clinical trial. A Phase II clinical trials looks at how well an investigational drug works and if it works to treat a specific cancer. SU011248 is an investigational drug. -Investigational- means that the drug is still being studied. It also means that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if the drug is effective for treating different types of cancer. It also means that FDA (the U.S. Food and Drug Administration) has not yet approved SU011248 (SUTENT) for your type of cancer. The FDA has approved SU011248 (Sutent) for treatment of patients with gastrointestinal stromal tumors (GIST), a rare stomach cancer, and advanced kidney cancer. Pfizer is providing the study drug and funding for the study. Volunteers will be involved in this study for about 1 year. There will be about 50 people taking part in this study at all sites. About 20 people will be taking part at Vanderbilt.

Criteria
 Inclusion Criteria:

 • History of primary mucosal or acral/lentiginous melanoma

 • Histologically documented stage III unresectable or IV metastatic melanoma

 • ECOG Performance Status 0,1 or 2

 • Estimated life expectancy of 6 months or greater

 • 18 years of age or older

 • Lab values as outlined in protocol

 • Tumor blocks or slides must be available of either primary or metastatic tumor site for c-kit mutation testing

 • Negative pregnancy test within 48 hours of starting treatment

 • At least one measurable site of disease as defined by at least 1cm in greatest dimension

 Exclusion Criteria:

 • Severe and/or uncontrolled medical disease

 • Pregnant or nursing mothers

 • Known brain metastasis. History of or known spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening CT or MRI scan

 • Less than 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or cervical carcinoma in situ

 • Grade III/IV cardiac problems as defined by the New York Heart Association Criteria

 • Ongoing cardiac dysrhythmias of grade 2 or greater, atrial fibrillation, QTc interval >450msec for males of >470 msec for females

 • Hypertension that cannot be controlled by medication

 • Any of the following within 12 months prior to starting treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism

 • NCI CTCAE version 3.0 grade 3 hemorrhage within 4 weeks of starting the study treatment

 • Concurrent treatment with warfarin

 • Prior treatment with SU011248 or any other antiangiogenic agent

 • No H2 blockers or proton pump inhibitors

 • Known chronic liver disease

 • Known HIV infection

 • Previous radiotherapy to 25% or more of the bone marrow and/or radiation therapy within 4 weeks prior to study entry

 • Major surgery within 4 weeks prior to study entry

 • Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication