Study to compare the efficacy and safety of masitinib to placebo in patients with localized, primary Gastrointestinal Stromal Tumor (GIST) after complete surgery and with high risk of recurrence
- Conditions
- Gastrointestinal Stromal Tumor (GIST)MedDRA version: 22.0Level: LLTClassification code 10071653Term: Gastrointestinal stromal cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-004162-34-IT
- 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
- 330
1.Patient with histologic diagnosis of localized, primary GIST
2.Patient with measurable primary tumor lesion using conventional techniques or spiral CT scan assessed before tumor resection
3.Imatinib-naïve patient in case imatinib is not available therapy OR Patient stopped imatinib as adjuvant therapy for reasons other than progression (i.e. adverse events, patient decision, patients who received a full course of imatinib as adjuvant therapy
4.Patient with a high risk of recurrence, i.e., patients with primary tumor diameter > 5 cm and mitotic count > 5/50 HPF, or tumor diameter > 10 cm and any mitotic count, or tumor of any size with mitotic count > 10/50 HPF, or tumors that have ruptured into the peritoneal cavity
5.Patient without peritoneal or distant metastasis
6.Patient with c-kit (CD117) positive primary tumor detected immuno-histochemically
7.Patient after gross tumor resection (regardless of microscopic margins, (R0 resection: negative microscopic margins or R1 resection: positive microscopic margins)
8.Patient free of tumor by post-operative imaging that included a baseline chest x-ray (or chest CT) and a post-operative abdomen and pelvis CT scan with intravenous and oral contrast or MRI with intravenous contrast within 28 days before the randomization
9.Patient with ECOG = 2
10.Patient with adequate organ functions:
•Absolute neutrophils count (ANC) = 1.5 x 109/L
•Hemoglobin = 10 g/dL
•Platelets (PTL) = 75 x 109/L
•AST/ALT = 3x ULN
•Gamma GT < 2.5 x ULN
•Bilirubin = 1.5x ULN
•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
11.Patient with life expectancy > 3 months
12.Male or female patient, age >18 years
13.Patient weight > 40 kg and BMI > 18 kg/m²
14.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: (listed)
Male patients must use medically acceptable methods of contraception if your 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: (listed).
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:(listed)
15.Patient able and willing to comply with study procedures as per protocol
16.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
17.Patient able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures are performed. 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
1.Patient with metastases of the primary GIST tumor
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 progressed under imatinib as adjuvant therapy
4.Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis
5.Patient presenting with cardiac disorders defined by at least one of the following conditions:
• Patient with left ventricular ejection fraction (LVEF) <50%
• Patient with recent cardiac history (within 6 months) of:
oAcute coronary syndrome
oAcute heart failure (class III or IV of the NYHA classification)
oSignificant 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 etiology within 3 months
• Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertension
6.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
7.Pregnant, or nursing female patient
Previous treatment
8.Patient with positive test for hepatitis B virus surface antigen (HBVsAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection - at the screening visit.
9.Patient with known history of positive testing for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
10.Patient who is eligible for imatinib adjuvant treatment.
1.Patient previously treated with chemotherapy, radiation therapy, or investigational treatment following surgery
Wash-out
1.Treatment with any investigational agent within 4 weeks prior to Baseline visit
2.For patients treated with imatinib as adjuvant therapy, end of imatinib treatment must be between 5 days and 12 weeks prior to baseline
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 and safety of masitinib at 4.5 mg/kg/day with a switch after 12 weeks of treatment to 6 mg/kg/day to placebo.;Secondary Objective: The objective is to compare the efficacy and safety of masitinib at 4.5 mg/kg/day with a switch after 12 weeks of treatment to 6 mg/kg/day to placebo.;Primary end point(s): Recurrence Free Survival (RFS) as evaluated by independent review;Timepoint(s) of evaluation of this end point: Recurrence Free Survival (RFS) is defined as the time from the date of randomization to the date of death due to any cause during the study or<br>to the time of development of tumor recurrence, whichever comes first.<br>Recurrence is defined as recurrence of primary tumor or emergence of new tumor assessed by CT scan and evaluated by the independent review.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): ¿ Overall Survival (OS) defined as the time from the date of<br>randomization to the date of documented death.<br>¿ Time To Recurrence (TTR) as evaluated by independent review and<br>investigator<br>¿ Safety profile using the NCI CTC v4.0 classification;Timepoint(s) of evaluation of this end point: week 12