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

• Register: EUCTR
• Last refreshed on: 10 July 2015
• Main ID: EUCTR2013-004162-34-CZ
• Date of registration: 06/11/2014
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: 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
• Scientific title: A prospective, multicenter, randomized, double-blind, 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
• Date of first enrolment: 13/04/2015
• Target sample size: 330
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004162-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Argentina, Austria, Belgium, Canada, Chile, China, Cyprus, Czech Republic, France, Germany, Greece, Hungary, India, Indonesia, Italy, Morocco, Netherlands, Peru, Philippines, Poland, Russian Federation, Spain, Taiwan, Tunisia, Ukraine, United Kingdom, United States

Contacts

• Name: Urszula Bogucka
• Affiliation: AB Science

• Name: Urszula Bogucka
• Affiliation: AB Science

Key inclusion & exclusion 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:
1. Patient avec confirmation histologique d’un GIST primaire localisée 2. Patient ayant des lésions tumorales primaires utilisant les techniques de mesure conventionnelles ou en utilisant un scanner spiralé avant résection de la tumeur 3. Patient ayant arête l’imatinib en adjuvant thérapie sans progression OU patient non éligible à l’imatinib en adjuvant thérapie 4. Patient avec un risqué élevé de récidive : patient avec une tumeur primaire d’un diamètre > 5 cm et un indice mitotique > 5/50 HPF, ou une tumeur d’un diamètre > 10 cm quelque soit l’indice mitotique, ou quelque soit la taille de la tumeur avec un indice mitotique > 10/50 HPF ou des tumeurs qui sont rompues dans la cavité péritonéale 5. Patient sans métastases péritonéales 6. Patient ayant une tumeur C-kit (CD117) positive détectée de façon immuno-histochimique 7. Patient après résection de la tumeur brut (indépendamment des marges microscopiques) dans les 14-70 derniers jours après la chirurgie (résection R0: marges microscopiques négatives ou résection R1: marges microscopiques positives) 8. Patient sans tumeur vérifiée par imagerie post-opératoire qui comprend une radiographie thoracique (ou scanner) et un scanner post-opératoire de l’abdomen et du bassin et du bassin avec contraste (intraveineux et oral) ou une 'IRM avec contraste intraveineux dans les 28 jours avant la randomisation 9. Patient ayant un ECOG = 2 10. Patient ayant des fonctions organiques adéquates
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 330
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 230

Exclusion criteria:
. 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: o Acute coronary syndrome o Acute heart failure (class III or IV of the NYHA classification) o 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 severe hypertension, according to the judgment of the investigator, or symptomatic 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


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

Health Condition(s) or Problem(s) studied

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

stromal gastrointestinal cancer
MedDRA version: 17.1 Level: LLT Classification code 10062427 Term: Gastrointestinal stromal tumor System Organ Class: 100000004864

Intervention(s)

Product Name: masitinib 100 mg
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1003 (name of active substance)
Other descriptive name: AB1010 (name of finished product)
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: masitinib 200 mg
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: masitinib mesylate
CAS Number: 790299-79-5
Current Sponsor code: AB1003
Other descriptive name: AB1010 (name of finished product)
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Recurrence Free Survival (RFS) is defined as the time from the date of randomization to the date of death due to any cause during the study or to the time of development of tumor recurrence, whichever comes first. Recurrence is defined as recurrence of primary tumor or emergence of new tumor assessed by CT scan

Main Objective: The objective is to compare the efficacy of masitinib at 4.5 mg/kg/day to placebo

Secondary Objective: The objective is to compare the safety of masitinib at 4.5 mg/kg/day to placebo

Primary end point(s): Recurrence Free Survival (RFS) as evaluated by independent review

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 12

Secondary end point(s): • Overall Survival (OS) defined as the time from the date of randomization to the date of documented death. • Time To Recurrence (TTR) as evaluated by independent review and investigator • Safety profile using the NCI CTC v4.0 classification

Secondary ID(s)

AB12004

2013-004162-34-ES

Source(s) of Monetary Support

AB Science