A prospective, multicenter, randomized, open-label, active-controlled, phase III study to compare efficacy and safety of masitinib to imatinib at 400 or 600 mg in treatment of patients with gastro-intestinal stromal tumour in first line medical treatment

Phase 1

• Conditions: gastro-intestinal stromal tumour; MedDRA version: 20.0 Level: LLT Classification code 10062427 Term: Gastrointestinal stromal tumor System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2008-000973-40-DE
• Lead Sponsor: AB SCIENCE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2010-06-17
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 450

Inclusion Criteria

1.Histologically proven, metastatic or locally advanced non resectable, or recurrent post surgery GIST
2.Naïve patient or patient previously treated with imatinib as neoadjuvant/adjuvant who relapsed after imatinib discontinuation
3.Measurable tumour lesions with longest diameter = 20 mm using conventional techniques or = 10 mm with spiral CT scan according RECIST criteria
4.C-Kit (CD117) positive tumours detected by immuno-histochemically or PDGFR positive if c-kit negative
5.ECOG < 1
6.Patient with adequate organ function:
•Absolute neutrophil count (ANC) = 1.5 x 109/L
•Haemoglobin = 10 g/dL
•Platelets (PTL) = 75 x 109/L
•AST/ALT = 3x ULN (= 5 x ULN in case of liver metastases)
•Gamma GT = 2.5 x ULN (= 5 x ULN in case of liver metastases)
•Bilirubin = 1.5x ULN (= 3 x ULN in case of liver metastases)
•Normal Creatinine or if abnormal creatinine, Creatinine clearance = 50 mL/min (Cockcroft and Gault formula)
•Albumin > 1 x LLN
•Proteinuria < 30 mg/dL (1+) on the dipstick; in case of proteinuria = 30 mg/dL, 24 hours proteinuria must be = 1.5g
7.Patient with life expectancy > 3 months
8.Men or women, age =18 years
9.Men and women of childbearing potential must agree to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake. Female patient of childbearing potential must have a negative pregnancy test at screening and baseline.
10.Patient should be able and willing to comply with study procedures as per protocol.
11.Patient should be able to understand, sign, and date the written voluntary informed consent form at screening visit prior to any protocol-specific procedures. If the patient is deemed by the treating physician to be cognitively impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable, the designated legal guardian must sign the informed consent.
12.Patient able to understand the patient card and to follow the patient card procedures, in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity, during the first 2 months of treatment.
13.Patient weight > 40 kg and BMI > 18 kg/m²

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 350

Exclusion Criteria

1.Patient previously treated by tyrosine kinase inhibitors except imatinib in case of inclusion criteria 2
2.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
3.Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis
4.Patient presenting with cardiac disorders defined by at least one of the following conditions:
•Patient with recent cardiac history (within 6 months) of:
-Acute coronary syndrome
-Acute heart failure (class III or IV of the NYHA classification)
-Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
•Patient with cardiac failure class III or IV of the NYHA classification.
•Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block).
•Syncope without known aetiology within 3 months.
•Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertension.
5.Patient with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent
6.Patient with any condition that the physician judges as detrimental to subjects participating in this study, including any clinically important deviations from normal clinical laboratory values or concurrent medical events
7.Females who are pregnant, breast feeding or planning a pregnancy during the course of the study

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objective is to compare the efficacy of masitinib at 6 and 7.5 mg/kg/day to imatinib at 400 or 600 mg, in patients with gastro-intestinal stromal tumour in first line medical treatment. ;Secondary Objective: The objective is to compare the safety of masitinib at 6 and 7.5 mg/kg/day to imatinib at 400 or 600 mg, in patients with gastro-intestinal stromal tumour in first line medical treatment. ;Primary end point(s): Overall Progression Free Survival (PFS) according to central review;Timepoint(s) of evaluation of this end point: week 24