E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
stromal gastrointestinal cancer (GIST) |
|
E.1.1.1 | Medical condition in easily understood language |
stromal gastrointestinal cancer (GIST) |
|
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 | LLT |
E.1.2 | Classification code | 10062427 |
E.1.2 | Term | Gastrointestinal stromal tumor |
E.1.2 | System Organ Class | 100000004864 |
|
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 |
Primary objective: the efficacy of masitinib 12 mg/kg/day in comparison with sunitinib 50 mg/day in patients with stromal gastrintestinal cancer previously progressed after treatment with imatinib |
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives: safety and quality of life |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient with histological proven metastatic GIST or non-operable locally advanced GIST
2. Patient with measurable tumor lesions with longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan according to RECIST 1.1
3. Patient with C-kit (CD117) positive tumour detected immuno-histochemically
4. Patient after at least one progression with imatinib at at a dose up to 800mg. 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/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 (≤ 3xULN 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 > 6 months
8. Male or female patient, age >18 years
9. Patient BMI > 18 kg/m² and weight > 40 kg
10. Male and female patient of child bearing 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 paitent of child bearing potential must have a negative pregnancy test at screening and baseline.
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 in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity, during the first 2 months of treatment
14. Patient covered by insurance reimbursing sunitinib
|
|
E.4 | Principal exclusion criteria |
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 ot the judgement 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
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Efficacy
- Survival rate at weeks 8, 16, 24, and then every 12 weeks
- Overall Progression Free Survival (PFS) as evaluated by independent review and investigator
- PFS rate at weeks 8, 16, 24, and then every 12 weeks as evaluated by independent review and investigator
- Overall time to progression (TTP) as evaluated by independent review and investigator
- TTP rate at weeks 8, 16, 24, and then every 12 weeks as evaluated by independent review and investigator
- Overall Time to treatment failure (TTF)
- TTF rate at weeks 8, 16, 24, and then every 12 weeks
- Best Response rate as evaluated by independent review and investigator
- Objective Response rate: Complete Response (CR) or Partial response (PR) at weeks 8, 16, 24, and then every 12 weeks as evaluated by independent review and investigator
- Disease Control rate: CR + PR + stable disease (SD) at weeks 8, 16, 24, and then every 12 weeks as evaluated by independent review and investigator
• Safety
- Discontinuation for related adverse event (DAES)
- DAES rate at weeks 8, 16, 24, and then every 12 weeks
- Total Event Free Survival (TEFS)
- TEFS rate at weeks 8, 16, 24, and then every 12 weeks
- Safety Event Free Survival (SEFS)
- SEFS rate at weeks 8, 16, 24, and then every 12 weeks
- Related Grade 3 non haematological or any related grade 4 related adverse event
- Safety profile using the NCI CTCAE v4.03 classification
Quality of life
- Quality of Life according to the EORTC QLQ-C30 questionnaire at week 8, 16, 24 and then every 12 weeks
- ECOG Performance Status at week 8, 16, 24 and then every 12 weeks
|
|
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 | Yes |
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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
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 | 2 |
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 | 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 |
|
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
|
Patient will be treated untill disease progression, toxicity without clinical benefit, or 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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |