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A prospective, multicenter, randomised, 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 resistant to imatinib

Conditions
Gastrointestinal stromal tumor resistant to imatinib
MedDRA version: 14.0Level: LLTClassification code 10062427Term: Gastrointestinal stromal tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2011-001790-41-FR
Lead Sponsor
AB Science
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
210
Inclusion Criteria

1. Patient with histological proven non-operable locally advanced or metastatic GIST
2. Patient with measurable tumor lesions with longest diameter = 20 mm using conventional techniques or = 10 mm with spiral CT scan according RECIST criteria
3. Patient with C-kit (CD117) positive tumour detected immuno-histochemically
4. Patients resistant to imatinib at dose of 400 (for all countries) or 600 mg/day (only for US). Resistance is defined as a RECIST 1.1 disease progression under imatinib treatment
5. Patient with ECOG = 2
6. Patient with adequate organ functions:
• Absolute neutrophils count (ANC) = 1.5 x 109/L
• Haemoglobin = 10 g/dL
• Platelets (PTL) = 75 x 109/L
• AST/ALT = 2.5x ULN (= 5 x ULN in case of liver metastases)
• Gamma GT < 3 x ULN (< 5 x ULN in case of liver metastases)
• Bilirubin = 1.5x ULN (= 3xULN in case of liver metastases)
• Creatinine clearance = 50 mL/min (Cockcroft and Gault formula)
• Albumin > 1 x LLN
• Urea = 2 x ULN
• Proteinuria < 30 mg/mL (1+) on the dipstick. If proteinuria is = 1+ on the dipstick, 24 hours proteinuria must be < 1.5g/24 hours
7. Patient with life expectancy > 6 months
8. Male or female patient, age >18 years
9. Patient with a BMI > 18 kg/m² and weighing at least 40kg
10. Male and female patient of child bearing potential, (entering the study after a menstrual period and who have a negative pregnancy test) 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.
11. Patient able and willing to comply with study procedures as per protocol
12. Patient able to understand, sign, and date the written informed consent form at screening visit prior to any protocol-specific procedures
13. Patient affiliated to a social security regimen (for France only) and/or covered by insurance reimbursing sunitinib

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 210
F.1.3 Elderly (>=65 years)
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. 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
2. Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis
3. 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
4. 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
5. Pregnant, or nursing female patient

• Previous treatment
6. Patient previously treated with a dose of imatinib >600mg (only for US) or >400mg (outside of the US)
7. Patient intolerant to imatinib
8. Patients non resistant to imatinib
9. Previous treatment with sunitinib or kinase inhibitor other than imatinib

• Wash-out
10. Treatment with any investigational agent within 4 weeks prior to baseline
11. Previous imatinib treatment should be permanently discontinued within 4 days prior randomisation and patient should have recovered from potential toxicity related to imatinib

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To compare efficacy of masitinib at 12 mg/kg/day to sunitinib at 50 mg/day in treatment of patients with gastro-intestinal stromal tumor resistant to imatinib;Secondary Objective: To compare safety and quality of life of masitinib at 12 mg/kg/day to sunitinib at 50 mg/day in treatment of patients with gastro-intestinal stromal tumor resistant to imatinib.;Primary end point(s): Overall Progression Free Survival (PFS) as evaluated by independent review;Timepoint(s) of evaluation of this end point: Week 24
Secondary Outcome Measures
NameTimeMethod
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