Imatinib in Patients With Mucosal or Acral/Lentiginous Melanoma

Phase 2

Completed

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

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Treatment Arm	Imatinib	Imatinib

Primary Outcome Measures

Name	Time	Method
Best Overall Response	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).	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.

Secondary Outcome Measures

Name	Time	Method
Time to Progression	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).	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.
Overall Survival	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).	Overall survival (OS) is defined as the time from study entry to death or date last known alive.

Locations (5): MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
University of Chicago
🇺🇸
Chicago, Illinois, United States
H. Lee Moffitt Cancer Center
🇺🇸
Tampa, Florida, United States
University of Colorado at Denver Health Sciences Center
🇺🇸
Denver, Colorado, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States