A Phase 3 Study to Evaluate Efficacy and Safety of Masitinib in Comparison to Sunitinib in Patients With Gastrointestinal Stromal Tumour After Progression With Imatinib

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01694277
Recruitment Status : Unknown
Verified August 2013 by AB Science.
Recruitment status was:  Recruiting
First Posted : September 27, 2012
Last Update Posted : August 14, 2013
Information provided by (Responsible Party):
AB Science

Brief Summary:
The objective is to compare the efficacy and safety of masitinib at 12 mg/kg/day to sunitinib at 50 mg/day

Condition or disease Intervention/treatment Phase
Gastrointestinal Stromal Tumors Drug: Masitinib Drug: Sunitinib Phase 3

Detailed Description:

GISTs are uncommon visceral sarcomas that arise predominantly in the gastrointestinal 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 second line treatment of patients with GIST after progression with imatinib.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 208 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Multicenter, Randomized, 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 at 400mg as First Line Treatment
Study Start Date : April 2012
Estimated Primary Completion Date : January 2015
Estimated Study Completion Date : December 2015

Arm Intervention/treatment
Experimental: Masitinib
masitinib at 12 mg/kg/day
Drug: Masitinib
12 mg/kg/day

Active Comparator: Sunitinib
sunitinib at 50 mg/day
Drug: Sunitinib
50 mg/day

Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: up to 24 weeks ]
    Overall Survival (OS) is defined as the time from the date of randomization to the date of documented death

Secondary Outcome Measures :
  1. Time to Progression [ Time Frame: up to 24 weeks ]
    Time to Progression from the date of randomization until disease progression

  2. Overall Progression Free Survival (PFS) [ Time Frame: up to 24 weeks ]
    From the date of randomization to disease progression or death

  3. Survival rate [ Time Frame: up to 24 weeks ]
    from the date of randomization until death

  4. Objective Response Rate [ Time Frame: up to 24 weeks ]
    Partial response or total Response

  5. Control Disease Rate [ Time Frame: up to 24 weeks ]
    Disease Control documented partial response (PR), complete response (CR) or stable disease (SD

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 progression with to imatinib at the dose of 400 mg as first line treatment. Resistance 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
  7. Patient with life expectancy > 6 months
  8. Male or female patient, age >18 years
  9. Patient with a BMI > 18 kg/m² and weighing at least 40 kg
  10. Male and female patient of child bearing potential, (for female entering the study after a menstrual period and who have a negative pregnancy test at baseline) 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.
  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

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

Previous treatment

  1. Known hypersensitivity to sunitinib or masitinib or to any of the excipients
  2. Patient previously treated with a dose of imatinib > 400mg
  3. Patient intolerant to imatinib
  4. Previous treatment with sunitinib or kinase inhibitor other than imatinib


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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01694277

Contact: Axel Le Cesne, M.D., Ph.D. +33 1 42 11 43 16

Institut Bergonié Recruiting
Bordeaux, France, 33000
Sponsors and Collaborators
AB Science

Responsible Party: AB Science Identifier: NCT01694277     History of Changes
Other Study ID Numbers: AB11002
First Posted: September 27, 2012    Key Record Dates
Last Update Posted: August 14, 2013
Last Verified: August 2013

Keywords provided by AB Science:
Gastrointestinal Stromal Tumour
second line treatment
resistance to imatinib

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors