A prospective, multicenter, randomized, double blind, placebo-controlled, 2-parallel groups, phase 3 study to compare the efficacy and safety of masitinib in combination with FOLFIRI (irinotecan, 5-fluorouracil and folinic acid) to placebo in combination with FOLFIRI in second line treatment of patients with metastatic colorectal cancer

INTERVENTION: Product Name: masitinib 100mg Product Code: AB1010 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: MASITINIB CAS Number: 790299‐79‐5 Current Sponsor code: AB1010 Other descriptive name: MASITINIB Concentration unit: mg/kg milligram(s)/kilogram Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use Product Name: masitinib 200mg Product Code: AB1010 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: MASITINIB CAS Number: 790299‐79‐5 Current Sponsor code: AB1010 Other descriptive name: MASITINIB Concentration unit: mg/g milligram(s)/gram Concentration type: equal Concentration number: 200‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use CONDITION: Metastatic colorectal cancer after 1 previous line of treatment ; MedDRA version: 17.1 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864 Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: Overall survival (OS) Primary end point(s): ? Overall Survival (OS) is defined as the time from the randomization to the date of documented death Secondary Objective: Tumor assessment; ‐ Overall Progression Free Survival (PFS); ‐ PFS rate every 8 weeks ; ‐ Overall Time To Progression (TTP); ‐ TTP rate every 8 weeks ; ‐ Best response rate, Objective response rate (CR + PR) and Disease control rate (CR + PR + SD) every 8 weeks; ? Quality of life assessment at week every 8 weeks ; ‐ ECOG Performance Status; ‐ Quality of Life according to the EORTC QLQ‐C30; ‐ Analgesic intake; ‐ Pain improvement (VAS); ? Pharmacogenomic assessment (Relationship between genomic data and overall survival); ? Safety profile using the NCI CTCAE v4.02 classification Timepoint(s) of evaluation of this end point: Date of documented death SECONDARY OUTCOME: Secondary end point(s): ? Survival rate is defined as the rate of patients alive at each time point; ? Overall Progression Free Survival (PFS) is defined as the delay between the date of randomization to the date of documented progression or any cause of death during the study. Progression will be assessed by CT scan according to RECIST criteria version 1.1 as defined in table 5.; ? PFS rate is defined as the rate of patients without progression or death at each time point; ? Overall Time To Progression (TTP) is defined as the time from the date of randomization to the date of documented progression defined according to RECIST criteria version 1.1; ? TTP rate is defined as the rate of patients without documented progression at each time point; ? Best Response is defined as the best response (CR or PR or SD or PD) defined according to to RECIST criteria version 1.1 recorded from the start of the treatment until end of study.; ? Best Response rate is defined as the number of patients achieving the Best Response divided by the total number of patients in the population of analysis.; ? Objective response rate (CR + PR) is defined as the number of patients with documented partial response or complete response defined according to RECIST, divided by the number of randomized patients ; ? Disease control rate (CR + PR + SD) is defined as the number of patients with documented partial response, complete response or stable disease defined according to RECIST criteria version 1.1, divided by the number of patients randomized at each time point. Timepoint(s) of evaluation of this end point: Every 8 weeks INCLUSION CRITERIA: 1. Patient with non‐resectable metastatic colorectal cancer with histological or cytological documentation of adenocarcinoma of the colon or rectum 2. Metastatic disease not amenable to surgical resection with curative intent 3. Patient in second line treatment after progression according to RECIST criteria following administration of a standard chemotherapy regimen for treatment of metastatic disease 4. Patient with measurable lesions according to RECIST criteria (version 1.1) with spiral CT scan and defined as ?10 mm in longest diameter and 2X the slice thickness for extra nodal lesions and/or >15 mm in short axis diameter for nodal lesions 5. Patient eligible for a standard second line therapy with FOLFIRI 6. Patient with ECOG ? 2 7. Patient with adequate organ function ? Absolute neutrophils count (ANC) ? 1.5 x 109/L ? Haemoglobin ? 10 g/dl ? Platelets (PLT) ? 75 x 109/L ? AST/ALT ? 3 x ULN (? 5 x ULN in case of liver metastase