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-AT
• Lead Sponsor: AB SCIENCE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2010-06-30
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• 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
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.Female patient of childbearing potential (entering the study after a menstrual period and who have a negative pregnancy test), who agrees to use two highly effective 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. Acceptable forms of contraception include:
•A documented placement of an intrauterine device (IUD) or intrauterine system (IUS) and the use of a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository)
•Documented tubal ligation (female sterilization). In addition, a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository) should also be used
•Double barrier method: Condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository
•Any other contraceptive method with a documented failure rate of <1% per year
•Abstinence
Male patients must use medically acceptable methods of contraception if his female partner is pregnant, from the time of the first administration of the study drug until three months following administration of the last dose of study drug. Acceptable methods include:
• Condom;
•If you have undergone surgical sterilization (vasectomy with documentation of azoospermia) a condom should also be used.
Male patients must use two highly effective 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. The acceptable methods of contraception are as follows:
•Condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository;
•Surgical sterilization (vasectomy with documentation of azoospermia) and a barrie

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
Previous treatment
7.Treatment with any investigational agent within 4 weeks prior baseline
8.Treatment by imatinib as neoadjuvant/adjuvant therapy within 4 weeks prior baseline

Study & Design

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