Imatinib in Patients With Mucosal or Acral/Lentiginous Melanoma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Mucosal Melanoma, Acral/Lentiginous Melanoma, Chronically Sun Damaged Melanomas

Intervention / Treatment
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* Drug: Imatinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>Imatinib | Drug: Imatinib<br>* Imatinib was given at a dose of 400 mg orally daily (4 100mg pills). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Dosage may have been increased to twice daily if disease worsened and patient was in otherwise good clinical condition.<br>* Other names: Gleevec;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response | Best overall response (BOR) on treatment was based on RECIST 1.0 criteria. For target lesions, complete response (CR) is complete disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. CR or PR confirmation required within 4 weeks. Progressive disease (PD) is at least a 20% increase in the sum LD of target lesions from smallest sum LD as reference or the appearance of one or more new lesions. Stable disease (SD) is neither meeting PR or PD. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. CR is disappearance of all non-target lesions. | Disease was evaluated radiologically at baseline, after 6-weeks, and at 2-month intervals on treatment. Mean treatment duration was 4 months (range 1-11; amplified/mutated 3m/ 6m). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression | Time to progression (TTP) based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. | Disease was evaluated radiologically at baseline, after 6-weeks, and at 2-month intervals on treatment and every 3 months long-term. Mean treatment duration was 4 months (range 1-11; amplified/mutated 3m/ 6m). | 
| Overall Survival | Overall survival (OS) is defined as the time from study entry to death or date last known alive. | Patients were followed long-term every 3 months until first progression, death or lost to follow-up. Median survival follow-up was 10.6 months (range 3.7-27.1). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Imatinib, Gleevec