SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma

• To determine the response rate of this patient population to treatment with SU011248 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• To determine the time to progression of this patient population to treatment with SU011248 [ Time Frame: Years ] [ Designated as safety issue: No ]

The purpose of this study is to evaluate how effective SU011248 works in treating acral lentiginous and mucosal melanoma which has spread beyond the local region. SU011248 is a protein-tyrosine kinase inhibitor and acts as a c-kit inhibitor drug. It is believed to work by blocking signals on certain cancer cells which allow the malignant cells to multiply and spread due to a change in the genetic make up of the cancer cell.

• Participants will be given a bottle of SU011248 pills and will be asked to take pills once daily for 28 days on an ongoing basis. Participants will return every 28 days for new pills.
• During all treatment cycles, participants will have a physical exam and undergo blood tests at every visit.
• After a month of receiving the study drug participants will undergo a repeat PET scan to see if the drug has caused any early changes to their cancer.
• At week 8 a repeat chest, abdomen and pelvic CT will be performed.
• Participants will be on this research study for approximately one year.

• Mucosal Melanoma
• Acral/Lentiginous Melanoma

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

• Beth Israel Deaconess Medical Center
• Massachusetts General Hospital
• Pfizer