Imatinib in Patients With Mucosal or Acral/Lentiginous Melanoma

A Phase II Study of Imatinib in Patients With Mucosal or Acral/Lentiginous Melanoma and Melanomas That Arise on Chronically Sun Damaged Skin.

The purpose of this study is to evaluate how effective imatinib (Gleevec) is in treating acral/lentiginous and mucosal melanoma which has spread to other parts of the body in patients who's disease carries a c-kit mutation. Imatinib is a protein-kinase inhibitor. It is believed that imatinib may be effective in blocking signals on certain cancer cells which allow the malignant cells to multiply and spread.

OBJECTIVES:

Primary

• To determine the response rate of patients with metastatic mucosal, acral/lentiginous, or chronically sun damaged melanomas to treatment with of imatinib.
• To determine the time to progression.

Secondary

• 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.
• Tolerability of imatinib.
• To assess amplification of c-kit status through quantitative PCR and/or FISH and other related molecular pathway targets.
• To correlate c-kit amplification status with response to therapy.

Inclusion Criteria:

• Melanomas that arise on chronically sun damaged skin and have pathologic evidence of solar elastosis
• History of primary mucosal or acral/lentiginous melanoma
• Histologically documented stage IV metastatic melanoma
• ECOG performance status 0,1, or 2
• Estimated life expectancy of 6 months or greater
• Age 18 years or older
• Creatinine < 1.5 x ULN
• ANC > 1500 ul
• Platelets > 100,000 ul
• Total bilirubin, AST, and ALT < 2 x ULN
• Amylase and lipase < 1.5 x ULN
• C-kit mutation documented from either primary or metastatic tumor site
• > 4 weeks from prior chemotherapy or investigational drug
• At least one measurable site of disease as defined by at least 1 cm in greatest dimension

Exclusion Criteria:

• Severe and/or uncontrolled medical disease
• Pregnant or nursing mothers
• Any other significant medical, surgical, or psychiatric condition that my interfere with compliance
• Patient is < 5 years free of another primary malignancy except: basal cell skin cancer or a cervical carcinoma in situ
• Concurrent treatment with Warfarin
• Prior treatment with c-kit inhibitor
• Patient with Grade III/IV cardiac problems as defined by NYHA criteria
• No H2 blockers or proton pump inhibitors
• Known brain metastasis
• Known chronic liver disease
• Known diagnosis of HIV infection
• Previous radiotherapy to > 25% of the bone marrow
• Major surgery within 2 weeks prior to study entry
• Patient has received any other investigational agent within 28 days of first study drug dosing
• Chemotherapy within 4 weeks prior to study entry