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Masitinib vs Placebo - Phase III Study to Compare the Efficacy and Safety of Masitinib to Placebo in Patients With Localized, Primary GIST After Complete Surgery and With High Risk of Recurrence

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified December 2013 by AB Science
Sponsor:
Information provided by (Responsible Party):
AB Science
ClinicalTrials.gov Identifier:
NCT02009423
First received: November 28, 2013
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

The objective is to compare the efficacy and safety of masitinib at 4.5 mg/kg/day to placebo.


Condition Intervention Phase
Gastro-Intestinal Stromal Tumour
Drug: Masitinib
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Prospective, Multicenter, Randomised, Double-blinded, Placebo-controlled, Two-parallel Groups, Phase III Study to Compare the Efficacy and Safety of Masitinib to Placebo in Patients With Localized, Primary Gastrointestinal Stromal Tumor (GIST) After Complete Surgery and With High Risk of Recurrence

Resource links provided by NLM:


Further study details as provided by AB Science:

Primary Outcome Measures:
  • Recurrence Free Survival (RFS) [ Time Frame: Until tumor recurrence (e.g. up to 24 months) ] [ Designated as safety issue: No ]
    e.g. from date of randomization until the date of first documented progression


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: until death of the patient (e.g. up to 24 months) ] [ Designated as safety issue: No ]
    e.g. from the date of randomization to the date of documented death

  • Time To Recurrence (TTR) [ Time Frame: until time of recurrence (e.g. up to 24 months) ] [ Designated as safety issue: No ]
    e.g. from the date of randomization to the date of documented tumor recurrence during the study as evaluated by independent review and investigator

  • Quality of Life [ Time Frame: between baseline and each patient visit (e.g. up to 24 months) ] [ Designated as safety issue: No ]
  • Safety profile [ Time Frame: until last patient visit (e.g. up to 24 months) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 330
Study Start Date: January 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Masitinib
masitinib-treatment arm
Drug: Masitinib
Placebo Comparator: Placebo
placebo-treatment arm
Drug: Placebo

Detailed Description:

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 domaine. 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 adjuvant therapy for patient after complete surgery and with high risk of relapse.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient with histologic diagnosis of localized, primary GIST
  2. Patient with measurable primary tumor lesion using conventional techniques or spiral CT scan assessed before tumor resection
  3. Patient stopped imatinib as adjuvant therapy without progression OR patient not eligible for imatinib as adjuvant therapy
  4. Patient with a high risk of recurrence, i.e., patients with primary tumor diameter > 5 cm and mitotic count > 5/50 HPF, or tumor diameter > 10 cm and any mitotic count, or tumor of any size with mitotic count > 10/50 HPF, or tumors that have ruptured into the peritoneal cavity
  5. Patient without peritoneal or distant metastasis
  6. Patient with c-kit (CD117) positive primary tumor detected immuno-histochemically
  7. Patient after gross tumor resection (regardless of microscopic margins) within the past 14-70 days after surgery (R0 resection: negative microscopic margins or R1 resection: positive microscopic margins)
  8. Patient free of tumor by post-operative imaging that included a baseline chest x-ray (or chest CT) and a post-operative abdomen and pelvis CT scan with intravenous and oral contrast or MRI with intravenous contrast within 28 days before the randomization
  9. Patient with ECOG ≤ 2
  10. Patient with adequate organ functions:

    • Absolute neutrophils count (ANC) ≥ 1.5 x 109/L
    • Hemoglobin ≥ 10 g/dL
    • Platelets (PTL) ≥ 75 x 109/L
    • AST/ALT ≤ 3x ULN
    • Gamma GT < 2.5 x ULN
    • Bilirubin ≤ 1.5x ULN
    • 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
  11. Patient with life expectancy > 3 months
  12. Male or female patient, age >18 years
  13. Patient weight > 40 kg and BMI > 18 kg/m²
  14. 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 patient of child bearing potential must have a negative pregnancy test at screening and baseline
  15. Patient able and willing to comply with study procedures as per protocol
  16. 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
  17. Patient able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures are performed. If the patient is deemed by the treating physician to be cognitively impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable, the designated legal guardian must sign the informed consent
  18. Patient covered by insurance

Exclusion Criteria:

  1. Patient with metastases of the primary GIST tumor
  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 progressed under imatinib as adjuvant therapy
  4. Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis
  5. 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 etiology within 3 months
    • Uncontrolled hypertension or symptomatic hypertension, where hypertension is defined by systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg and uncontrolled means that SBP lower than 140 mmHg and DBP lower than 90 mmHg are not achieved despite anti-hypertensive drugs, whatever the reason of failure (inadequate treatment, poor compliance, secondary hypertension or resistant hypertension).
  6. 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
  7. Pregnant, or nursing female patient

Previous treatment

1. Patient previously treated with chemotherapy, radiation therapy, or investigational treatment following surgery

Wash-out

  1. Treatment with any investigational agent within 4 weeks prior to Baseline visit
  2. For patients treated with imatinib as adjuvant therapy, end of imatinib treatment must be between 5 days and 12 weeks prior to baseline
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: AB Science
ClinicalTrials.gov Identifier: NCT02009423     History of Changes
Other Study ID Numbers: AB12004
Study First Received: November 28, 2013
Last Updated: December 9, 2013
Health Authority: United States: Food and Drug Administration / France: ANSM / Spain: Agencia espanola de medicamentes y productes sanitarios / UK: MHRA / Germany: BfArM) / Austria: BASG) / Belgium: FAMHP / Italy : AIFA / Netherlands : CCMO

Keywords provided by AB Science:
Gastro-Intestinal Stromal Tumour, GIST, localized primary tumor, complete surgery, adjuvant therapy.

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Recurrence
Digestive System Diseases
Digestive System Neoplasms
Disease Attributes
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Pathologic Processes

ClinicalTrials.gov processed this record on November 20, 2014