Study to compare the safety and efficacy of masitinib to sunitinib in patients with gastrointestinal stromal tumor after progression with imatinib.

• Register: EUCTR
• Last refreshed on: 14 March 2016
• Main ID: EUCTR2011-001790-41-GB
• Date of registration: 14/05/2013
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: Study to compare the safety and efficacy of masitinib to sunitinib in patients with gastrointestinal stromal tumor after progression with imatinib.
• Scientific title: A prospective, multicenter, randomised, open-label, active-controlled, two-parallel groups, phase 3 study to compare the efficacy and safety of masitinib to sunitinib in patients with gastrointestinal stromal tumor after progression with imatinib. - AB11002 - Second line of treatment for GIST
• Date of first enrolment: 23/12/2013
• Target sample size: 350
• 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: no Number of treatment arms in the trial: 2

Countries of recruitment

Austria, Belgium, Canada, France, Germany, Greece, Italy, Netherlands, Spain, United Kingdom, United States

Contacts

• Name: Project Manager (I Losikhin)
• Affiliation: AB Science

• Name: Project Manager (I Losikhin)
• 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 =(greater than or equal to) 20 mm using conventional techniques or = 10 mm with spiral CT scan according RECIST 1.1
3. Patient with C-kit (CD117) positive tumour detected immuno-histochemically
4. Patient after at least one progression with imatinib at a dose up to 800 mg. 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 and 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/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 > 3 months
8. Male or female patient, age >18 years
9. Patient with a BMI > 18 kg/m² and weighing at least 40kg
10. Contraception:
Female patient of childbearing potential (entering the study after a menstrual period and who have a negative pregnancy test), who agrees to use two highly effective 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.
Male patient with a female partner of childbearing potential who agrees to use a highly effective method of contraception and an acceptable method of contraception by his female partner during the study and for 3 months after the last treatment intake or who agrees to use an acceptable method of contraception and a highly effective method of contraception by his female partner during the study and for 3 months after the last treatment intake.
Highly effective methods of contraception include:
- Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal
- Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable
- Intrauterine device (IUD)
- Intrauterine hormone-releasing system (IUS)
- Bilateral tubal occlusion
- Vasectomized male (azoospermia assessed medically)
- Sexual abstinence (Its reliability should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient)
Acceptable methods of contraception include:
- Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action
- Male or female condom with or without spermicide
- Cap, diaphragm, or sponge with spermicide
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.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Numb
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 to the judgment 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

For the QT/QTc study
1. Patients with a marked prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval > 450 milliseconds)
2. Patient wih a history of additional risk factors for torsades de pointe (e.g. heart failure, hypokalemia, family history of Long QT Syndrome)
3. Patients using concomitant medications that prolong the QT/QTc interval (the list of medications is provided in the section “concomitant treatments”)

Previous treatment
1. Known hypersensitivity to sunitinib or masitinib or to any of the excipients
2. Patient previously treated with a dose of imatinib > 800 mg
3. Previous treatment with sunitinib or kinase inhibitor other than imatinib

Wash-out
1. Treatment with any investigational agent within 4 weeks prior to baseline
2. Previous imatinib treatment should be permanently discontinued within 4 days prior randomisation and patient should have recovered from potential toxicity related to imatinib


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

Health Condition(s) or Problem(s) studied

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

Gastrointestinal stromal tumor resistant to imatinib
MedDRA version: 18.1 Level: LLT Classification code 10062427 Term: Gastrointestinal stromal tumor System Organ Class: 100000004864

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: AB1010
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: AB1010
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Main Objective: The objective is to compare efficacy of masitinib at 12 mg/kg/day to sunitinib at 50 mg/day in treatment of patients with gastro-intestinal stromal tumor resistant to imatinib by assessing the Overall Survival (OS).

Secondary Objective: 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 rel

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

Timepoint(s) of evaluation of this end point: At the end of the study statistical analysis will be performed to determine if there is a difference in overall survival between patients receiving masitinib and those receiving sunitinib.

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: At the end of the study statistical analysis will be performed to determine if there is a difference in overall survival between patients receiving masitinib and those receiving sunitinib.

Secondary ID(s)

2011-001790-41-FR

AB11002

Source(s) of Monetary Support

AB Science