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

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

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Melanoma
• Intervention / Treatment: Drug: Masitinib; Drug: Dacarbazine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 134
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Hradec Králové, Czechia, 500 12
    • University Hospital Hradec Kralove
• France
  • Bordeaux, France, 33075
    • Hopital Saint Andre
  • Le Mans, France, 72037
    • Centre Hospitalier Le Mans
  • Marseille, France, 13274
    • Hôpital Sainte Marguerite
• Germany
  • Münster, Germany, 48149
    • Klinik und Poliklinik für Hautkrankheiten
• Italy
  • Milano, Italy, 20141
    • Istituto Europeo di Oncologia
• Russian Federation
  • Moscow, Russian Federation, 115478
    • N.N.Blokhin Russian Cancer Research Centre
• Spain
  • Valencia, Spain, 46014
    • Hospital General de Valencia
• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Blumenthal Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Masitinib; Participants receive masitinib (7.5 mg/kg/day), given orally twice daily.	Drug: Masitinib; Masitinib 7.5 mg/kg/day; Other Names: AB1010
Active Comparator: Dacarbazine; 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; IV bolus at 1,000 mg/m2 once every 3 weeks; Other Names: DTIC

What is the study measuring?

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
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
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

Collaborators and Investigators

• Sponsor: AB Science
• Investigators: Principal Investigator: Jean-Jacques GROB, MD, PhD, Hôpital Sainte Marguerite, Marseille, France

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2011
• Primary Completion (Actual): August 1, 2019
• Study Completion (Actual): August 1, 2019

Study Registration Dates

• First Submitted: August 6, 2010
• First Submitted That Met QC Criteria: January 19, 2011
• First Posted (Estimate): January 21, 2011

Study Record Updates

• Last Update Posted (Actual): November 5, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Melanoma; Tyrosine kinase inhibitor; c-Kit juxta membrane mutation
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Dacarbazine
• Other Study ID Numbers: AB08026