E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
gastro-intestinal stromal tumour |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051066 |
E.1.2 | Term | Gastrointestinal stromal tumour |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective is to compare the safety and efficacy of masitinib at 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 |
Tumour assessment: o Overall Survival (OS) o Time to progression (TTP). o Objective response rate (CR + PR) at month 6, 12, 18 and 24 o Control disease rate (CR + PR + SD) at month 6, 12, 18 and 24 o Best response • Association between PFS, OS, TTP, objective response, control disease and the phenotype of mutations on KIT/PDGF • Quality of life assessment: o Quality of Life according to the EORTC QLQ-C30 questionnaire at month 6, 12, 18 and 24 o ECOG Performance Status at month 6, 12, 18 and 24 • Safety o Safety profile using the NCI CTC v3.0 classification
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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. 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 immuno-histochemically or PDGF 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) ≥ 100 x 109/L • AST/ALT ≤ 2.5x ULN (≤ 5 x ULN in case of liver metastases) • bilirubin ≤ 1.5x ULN • creatinine clearance ≥ 50 mL/min (Cockcroft and Gault formula) • albumin > 0.75 x LLN • urea ≤ 1.5 x ULN • proteinuria < 30 mg/dL on the dipstick; in case of proteinuria ≥ 30 mg/dL, 24 hours proteinuria < 1.5g/24 hours 7. Patient with life expectancy > 6 months 8. Men or women, age >18 years 9. Men and women of childbearing 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. 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.
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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 with grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e. congestive heart failure, myocardial infarction within 6 months before baseline) 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 could be 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival (PFS). |
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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 | No |
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 | No |
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.8.3 |
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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | No |
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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Patients will be treated untill disease progression |
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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 | 2 |
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 | 2 |
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 |