| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| gastro-intestinal stromal tumour |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 18.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10051066 |
| E.1.2 | Term | Gastrointestinal stromal tumour |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 safety and efficacy of masitinib at 6 or
7.5 mg/kg/day to imatinib at 400 or 600 mg, in patients with gastrointestinal stromal tumour in first line medical treatment.
Primary objective is to demonstrate non-inferiority of masitinib over
imatinib on Progression Free Survival. |
|
| E.2.2 | Secondary objectives of the trial |
Secondary objectives are:
• To demonstrate superiority of masitinib over imatinib on Overall
Survival.
• To demonstrate superiority of masitinib over imatinib on Overall
Survival on the population of patients with mutation on c-kit Exon 11
• To select the most appropriate dose between 6 mg/kg/day and 7.5
mg/kg/day |
|
| 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 protocolspecific
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. Patients affiliated to a social security regimen
14. Patient weight > 40 kg and BMI > 18 kg/m² |
|
| 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
Wash out
1. Treatment with any investigational agent within 4 weeks prior
baseline
2. Treatment by imatinib as neoadjuvant/adjuvant therapy within 4
weeks prior baseline |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Overall Progression Free Survival (PFS) according to central review |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Progression Free Survival (PFS) is defined as the time from the date
of randomisation to the date of death during study or progression
assessed by CT scan according to RECIST 1.1 and based on central
review. |
|
| 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 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
|
| 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 | 2 |
| 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 | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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
|
Patients will be treated untill disease progression, limiting toxicity or
patient consent withdrawal |
|
| 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 |
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