Know Cancer

or
forgot password

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


Phase 3
18 Years
N/A
Open (Enrolling)
Both
Gastrointestinal Stromal Tumors

Thank you

Trial Information

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


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.


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

Wash-out

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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall Survival (OS)

Outcome Description:

Overall Survival (OS) is defined as the time from the date of randomization to the date of documented death

Outcome Time Frame:

up to 24 weeks

Safety Issue:

No

Authority:

United States: Food and Drug Administration

Study ID:

AB11002

NCT ID:

NCT01694277

Start Date:

September 2012

Completion Date:

December 2015

Related Keywords:

  • Gastrointestinal Stromal Tumors
  • Gastrointestinal Stromal Tumour
  • GIST
  • non-resectable
  • metastatic
  • second line treatment
  • resistance to imatinib
  • Gastrointestinal Stromal Tumors

Name

Location