This study aims to compare the efficienty and safety of masitinib at a dose of 12 mg/kg/dag to those of a standard treatment for GIST: sunitinib (Sutent) at a dose of 50 mg/day for 4 consecutive weeks followed by 2 weeks without medication. Masitinib and sunitinib will be administred untill disease progression in patients with GIST resitant to imatinib (Glivec)

• Register: EUCTR
• Last refreshed on: 14 September 2015
• Main ID: EUCTR2011-001790-41-BE
• Date of registration: 23/11/2012
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: This study aims to compare the efficienty and safety of masitinib at a dose of 12 mg/kg/dag to those of a standard treatment for GIST: sunitinib (Sutent) at a dose of 50 mg/day for 4 consecutive weeks followed by 2 weeks without medication. Masitinib and sunitinib will be administred untill disease progression in patients with GIST resitant to imatinib (Glivec)
• Scientific title: A prospective, multicenter, randomised, open-label, active controlled, 2 parallel groups, phase 3 study to compare the efficay and safety of masitinib to sunitinib in patients with gastrointestinal stromal tumor after progression with imitinib
• Date of first enrolment: 03/06/2013
• Target sample size: 208
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-001790-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: sunitinib (Sudent) Number of treatment arms in the trial: 2

Countries of recruitment

Austria, Belgium, France, Germany, Italy, Spain, United Kingdom, United States

Contacts

• Name: Alexander Buchkov
• Affiliation: AB Science

• Name: Alexander Buchkov
• Affiliation: AB Science

Key inclusion & exclusion criteria

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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 208
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

stromal gastrointestinal cancer (GIST)
MedDRA version: 18.0 Level: LLT Classification code 10062427 Term: Gastrointestinal stromal tumor System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: masitinib
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1003 (name of active substance)
Other descriptive name: AB1010 (name of finished product)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Name: masitinib
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1003 (name of active substance)
Other descriptive name: AB1010 (name of finished product)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Main Objective: 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

Timepoint(s) of evaluation of this end point: week 24

Primary end point(s): Overall survival (OS)

Secondary Objective: Secondary objectives: safety and quality of life

Secondary Outcome(s)

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

Timepoint(s) of evaluation of this end point: Week 24

Secondary ID(s)

AB11002

2011-001790-41-FR

Source(s) of Monetary Support

AB Science