Masitinib in Patients With Gastrointestinal Stromal Tumour After Progression With Imatinib

Study Overview
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Brief Summary
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The objective is to compare the efficacy and safety of masitinib at 12 mg/kg/day to sunitinib at 50 mg/day in the treatment of patients with gastro-intestinal stromal tumor (GIST) after progression with imatinib.

Detailed Description
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Masitinib is a selective tyrosine kinase inhibitor with potent activity against wild-type c-Kit, the juxta membrane domain of c-Kit, and PDGFR. Masitinib is also thought to promote survival via modulation of immunostimulation-mediated anticancer effects and modulation of the tumor microenvironment. The objective is to compare the efficacy and safety of masitinib at 12 mg/kg/day with respect to sunitinib at 50 mg/day in the treatment of imatinib-resistant gastro-intestinal stromal tumor (GIST).

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 to Sunitinib in Patients With Gastrointestinal Stromal Tumor After Progression With Imatinib at 400mg as First Line Treatment

Conditions
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Gastrointestinal Stromal Tumors

Intervention / Treatment
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* Drug: Masitinib
* Drug: Sunitinib


Participation Criteria
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Eligibility Criteria
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Main inclusion criteria include: Patient with histological proven metastatic GIST or non-operable locally advanced GIST Patient with c-Kit (CD117) positive tumor detected immuno-histochemically Patient after at least one progression with imatinib at a dose up to 800mg. Progression is defined as a RECIST 1.1 and/or CHOI disease progression while receiving imatinib treatment. Main exclusion criteria include: Patient treated for a cancer other than GIST within 5 years before enrolment, with the exception of basal cell carcinoma or cervical cancer in situ Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis Pregnant, or nursing female patient

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 (12 mg/kg/day), given orally twice daily. | Drug: Masitinib<br>* 12 mg/kg/day<br>* Other names: AB1010;|
| Active Comparator: Sunitinib<br>Participants receive sunitinib, given at 50 mg/day for 4 consecutive weeks out of 6 weeks, orally | Drug: Sunitinib<br>* 50 mg/day<br>* Other names: Sutent;|

What is the study measuring?
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Primary 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival rate | Survival rate is defined as the number of patients alive divided by the number of patients in the population of analysis. Assessed at week-8, -16, -24, and every 12 weeks thereafter. | Every 12 weeks until study completion, assessed for a maximum of 60 months | 
| Progression Free Survival (PFS) | Progression Free Survival is defined as the time from the randomization date until the date of earliest evidence of disease progression or death, for participants who progressed or died before subsequent cancer therapy. Disease progression will be assessed by the investigator on CT scan according to RECIST 1.1 criteria and/or CHOI criteria. | From day of randomization to disease progression or 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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Gastrointestinal Stromal Tumour, GIST, non-resectable, metastatic, second line treatment, resistance to imatinib, tyrosine kinase inhibitor