SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma

A Phase II Study of SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma

The purpose of this study is to evaluate how effective Sunitinib works in treating acral lentiginous and mucosal melanoma which has spread beyond the local region. Suninitib 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.

OBJECTIVES:

Primary

• To determine the proportion of participants with metastatic mucosal or acral/lentiginous melanoma who are alive and without disease progression at two months after beginning treatment with sunitinib.
• To determine the best overall response rate.

Secondary

• To determine the time to progression and overall survival.
• To correlate c-kit mutational status with response to therapy.
• To evaluate the use of FDG-PET scanning in determining early biologic response to therapy.
• To assess amplification of c-kit status through quantitative PCR and/or FISH and other related molecular pathway targets.

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