Masitinib in Non-Resectable or Metastatic Stage 3/4 Melanoma Carrying a Mutation in the Juxta Membrane Domain of c-Kit

Study Overview
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Brief Summary
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The objective is to assess the efficacy and safety of masitinib at 7.5 mg/kg/day in the treatment of patients with non-resectable or metastatic stage 3 or stage 4 melanoma carrying a mutation in the juxta membrane domain of c-Kit and who have not previously been treated for melanoma.

Detailed Description
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Masitinib is a selective tyrosine kinase inhibitor with potent activity against the juxta membrane domain of c-Kit. Masitinib is also thought to promote survival via modulation of immunostimulation-mediated anticancer effects and modulation of the tumor microenvironment. The objective of this study was to evaluate the efficacy and safety of masitinib with respect to dacarbazine in the treatment of non-resectable or metastatic stage 3 or stage 4 melanoma carrying a mutation in the juxta membrane domain of c-Kit. Following a protocol amendment, the dacarbarzine treatment group was closed and recruitment restricted to masitinib treatment of chemo-naïve (first-line) patients.

Official Title
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A Prospective, Multicenter, Randomized, Open-label, Active Controlled, Two-parallel Groups, Phase 3 Study to Compare the Efficacy and Safety of Masitinib at 7.5 mg/kg/Day to Dacarbazine in the Treatment of Patients With Non-resectable or Metastatic Stage 3 or Stage 4 Melanoma Carrying a Mutation in the Juxta Membrane Domain of C-kit

Conditions
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Metastatic Melanoma

Intervention / Treatment
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* Drug: Masitinib
* Drug: Dacarbazine


Participation Criteria
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Eligibility Criteria
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Main inclusion criteria include: Patient with histologically or cytologically confirmed non-resectable or metastatic stage 3 (non-resectable IIIB or IIIC, AJCC TNM staging system 7th edition) or stage 4 melanoma Patient with detectable c-Kit JM mutation (mutation in exon 9, 11 or 13) confirmed by DNA or RNA sequencing, which is expected to be mainly found after screening of mucosal or acral melanoma or melanoma on skin with chronic sun-induced damages (defined by a microscopically marked elastosis involving the skin surrounding their primary melanoma). Patient not previously treated for melanoma (first-line) Main exclusion criteria include: Pregnant, or nursing female patient Patient with active brain metastases. Prior treatment with a tyrosine kinase c-Kit inhibitor

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Masitinib<br>Participants receive masitinib (7.5 mg/kg/day), given orally twice daily. | Drug: Masitinib<br>* Masitinib 7.5 mg/kg/day<br>* Other names: AB1010;|
| Active Comparator: Dacarbazine<br>Participants receive dacarbazine, given via IV bolus at 1,000 mg/m2 once every 3 weeks. Following a protocol amendment, the dacarbarzine treatment group has been closed | Drug: Dacarbazine<br>* IV bolus at 1,000 mg/m2 once every 3 weeks<br>* Other names: DTIC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Estimated as the number of patients with documented partial response or complete response defined according to the RECIST criteria, divided by the number of randomized patients | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progression Free Survival (PFS) is defined as the delay between the date of randomization to the date of documented progression (according to RECIST) or any cause of death during the study. | From day of randomization to disease progression or death, assessed for a maximum of 60 months | 
| Overall Survival (OS) | Overall survival is defined as time in months from the randomization date to the date of death due to any cause. If a patient is not known to have died, then OS will be censored at the date of last known date patient alive. | From day of randomization to death, assessed for a maximum of 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma, Tyrosine kinase inhibitor, c-Kit juxta membrane mutation