Study to compare the safety and efficacy of masitinib to sunitinib in patients with gastrointestinal stromal tumor after progression with imatinib.
- Conditions
- Gastrointestinal stromal tumor resistant to imatinibMedDRA version: 18.1Level: LLTClassification code 10062427Term: Gastrointestinal stromal tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-001790-41-GB
- 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
- 350
1. Patient with histological proven metastatic GIST or non-operable locally advanced GIST
2. Patient with measurable tumor lesions with longest diameter =(greater than or equal to) 20 mm using conventional techniques or = 10 mm with spiral CT scan according RECIST 1.1
3. Patient with C-kit (CD117) positive tumour detected immuno-histochemically
4. Patient after at least one progression with imatinib at a dose up to 800 mg. Progression is defined as a RECIST 1.1 and/or CHOI disease progression while receiving 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 and 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/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 > 3 months
8. Male or female patient, age >18 years
9. Patient with a BMI > 18 kg/m² and weighing at least 40kg
10. Contraception:
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.
Male patient with a female partner of childbearing potential who agrees to use a highly effective method of contraception and an acceptable method of contraception by his female partner during the study and for 3 months after the last treatment intake or who agrees to use an acceptable method of contraception and a highly effective method of contraception by his female partner during the study and for 3 months after the last treatment intake.
Highly effective methods of contraception include:
- Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal
- Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable
- Intrauterine device (IUD)
- Intrauterine hormone-releasing system (IUS)
- Bilateral tubal occlusion
- Vasectomized male (azoospermia assessed medically)
- Sexual abstinence (Its reliability should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient)
Acceptable methods of contraception include:
- Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action
- Male or female condom with or without spermicide
- Cap, diaphragm, or sponge with spermicide
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 able to understand the patient card and to follow the patient card procedures.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Numb
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
For the QT/QTc study
1. Patients with a marked prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval > 450 milliseconds)
2. Patient wih a history of additional risk factors for torsades de pointe (e.g. heart failure, hypokalemia, family history of Long QT Syndrome)
3. Patients using concomitant medications that prolong the QT/QTc interval (the list of medications is provided in the section concomitant treatments”)
Previous treatment
1. Known hypersensitivity to sunitinib or masitinib or to any of the excipients
2. Patient previously treated with a dose of imatinib > 800 mg
3. Previous treatment with sunitinib or kinase inhibitor other than imatinib
Wash-out
1. Treatment with any investigational agent within 4 weeks prior to baseline
2. 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
Name Time Method
- Secondary Outcome Measures
Name Time Method