E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
gastro-intestinal stromal tumour |
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E.1.1.1 | Medical condition in easily understood language |
gastro-intestinal stromal tumour |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10062427 |
E.1.2 | Term | Gastrointestinal stromal tumor |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Progression Free Survival (PFS) according to central review |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Tumour assessment:
• Overall PFS according to local review
• PFS rate every 12 weeks according to central review and local review
• Overall Survival (OS)
• Survival rate every 12 weeks
• Overall Time to progression (TTP)
• TTP rate every 12 weeks according to central review and local review
• Overall Time to Treatment Failure (TTF)
• TTF rate every 12 weeks
• Response rate (CR + PR) disease control rate (CR + PR + SD) every 12 weeks
• Best response
• Association between PFS, OS, TTP, TTF, response and the phenotype of mutations on KIT/PDGFR
• Quality of life assessment:
• Quality of Life according to the EORTC QLQ-C30 questionnaire every 12 weeks
• ECOG Performance Status every 12 weeks
• Safety
• Safety profile using the NCI CTC v4.0 classification
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Belgium |
Canada |
France |
Germany |
Hungary |
Lebanon |
Netherlands |
Spain |
Thailand |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Until disease progression, limiting toxicity or patient consent withdrawal |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |