A Phase 3 Study to Evaluate Efficacy and Safety of Masitinib in Comparison to Imatinib in Patients With Gastro-Intestinal Stromal Tumour in First Line Medical Treatment

The objective of the study is to compare the efficacy and safety of masitinib to imatinib in patients with gastro-intestinal stromal tumour (GIST) in first line medical treatment.

GISTs are uncommon visceral sarcomas that arise predominantly in the gastro-intestinal tract. Most GIST cells are positive for c-kit (CD117), a cell surface antigen corresponding to the Stem Cell Factor (SCF) receptor. The receptor has an intracellular tyrosine kinase (TK) joined by a juxtamembrane domain. It is hypothesized that all malignant GIST cells harbor a mutation of c-kit, resulting in the activation of c-kit and cell division and tumour growth. Drugs that can selectively inhibit TKs are likely to be of benefit in GISTs. Masitinib (AB1010) is a TK inhibitor, selectively and effectively inhibiting c-kit. Imatinib is also a TK inhibitor indicated in the treatment of GIST. It might be associated with side effects and patients might develop a resistance to treatment over time. Based on pre-clinical and clinical studies, masitinib (AB1010) can be considered as a good candidate in the first line treatment of patients with GIST.

• Drug: masitinib (AB1010)
  masitinib (AB1010) 7.5 mg/kg/day, per os
  Other Name: AB1010
• Drug: imatinib
  imatinib 400 mg or 600 mg per day, per os

• Experimental: 1
  masitinib 7.5 mg/kg/day, per os
  Intervention: Drug: masitinib (AB1010)
• Active Comparator: 2
  imatinib 400 mg or 600 mg per day, per os
  Intervention: Drug: imatinib

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. C-Kit (CD117) positive tumours detected immuno-histochemically or PDGF positive if c-kit negative
4. Man or woman, age >18 years
5. Man and woman 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
6. Patient able and willing to comply with study procedures as per protocol
7. Patient able to understand, sign, and date the written voluntary informed consent form at screening visit prior to any protocol-specific procedures

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) 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
5. Treatment with any investigational agent within 4 weeks prior baseline
6. Treatment by imatinib as neoadjuvant/adjuvant therapy within 4 weeks prior baseline