Study to evaluate 3 type of treatment (masitinib + FOLFIRI, or masitinib alone, or Best suportiv care) in the treatment of patients with metastatic colorectal cancer that have received 2 or 3 previous therapies

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2013-000493-30-CZ
• Date of registration: 30/07/2015
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: Study to evaluate 3 type of treatment (masitinib + FOLFIRI, or masitinib alone, or Best suportiv care) in the treatment of patients with metastatic colorectal cancer that have received 2 or 3 previous therapies
• Scientific title: A prospective, multicentre, open-label, randomized, active-controlled, 3 parallel groups, phase 2 study to compare the efficacy and safety of masitinib in combination with FOLFIRI (irinotecan, 5-fluorouracil and folinic acid, versus masitinib alone, versus Best Supportive Care, in third or fourth line treatment of patients with metastatic colorectal cancer
• Date of first enrolment: 30/07/2015
• Target sample size: 150
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000493-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Best Supportive Care Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Algeria, Austria, Bulgaria, Canada, Czech Republic, France, Germany, Greece, Hungary, Ireland, Italy, Morocco, Portugal, Romania, Russian Federation, Serbia, Slovakia, Spain, Tunisia, United Kingdom, United States

Contacts

• Name: Alain Moussy
• Affiliation: AB Science

• Name: Alain Moussy
• Affiliation: AB Science

Key inclusion & exclusion criteria

Inclusion criteria:
INCLUSION CRITERIA
1. Patient with non-resectable metastatic colorectal cancer with histological or cytological documentation of adenocarcinoma of the colon or rectum
2. Patient in third line or fourth line treatment for metastatic colorectal cancer
? in failure of all available therapies : 5FU, irinotecan, oxalplatin +/- bevacizumab, +/- cetuximab, +/- panatumumab or other available combination of chemotherapy
? for which treatment by regorafenib is not recommended
3. Patient with measurable lesions according to RECIST criteria (version 1.1) with spiral CT scan and defined as ?10 mm in longest diameter and 2X the slice thickness for extra nodal lesions and/or >15 mm in short axis diameter for nodal lesions
4. Patient with ECOG = 2
5. Patient with adequate organ function
? Absolute neutrophils count (ANC) = 1.5 x 109/L
? Haemoglobin = 10 g/dL
? Platelets (PLT) = 75 x 109/L
? AST and ALT = 3 x ULN (= 5 x ULN in case of liver metastases)
? Gamma GT = 2.5 x ULN (= 5 x ULN in case of liver metastases)
? Bilirubin = 1.5x ULN (= 3xULN in case of liver metastases)
? Normal creatinine or if abnormal creatinine, creatinine clearance = 50 mL/min (Cockcroft and Gault formula)
? Albuminaemia > 1 x LLN
? Proteinuria < 30 mg/dL (1+) on the dipstick. If proteinuria is = 1+ on the dipstick, 24 hours proteinuria must be < 1.5g/24 hours
? For France only: Urea (BUN) = 2 x ULN (Upper Limit Range)
? Troponin T < 0.1 ng/mL or Troponin I < 0.35 ng/mL
? For US only: Troponin T < ULN (Upper Limit Range) or Troponin I < ULN (Upper Limit Range) (applicable in USA only)
6. Patient with life expectancy > 3 months
7. Patient weight > 40 kg and BMI > 18 kg/m²
8. Female or male patient = 18 years
9. Contraception
- Female patient of childbearing potential (entering the study after a menstrual period and who have a negative pregnancy test), who agrees to use twoa highly effective methods (one for the patient and one for the partner) of medically acceptable formsmethod of contraception and an acceptable method of contraception by her male partner during the study and for 3 months after the last treatment intake. Acceptable forms of contraception include:
- A documented placement of an intrauterine device (IUD) or intrauterine system (IUS) and the use of a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] usedMale patient with spermicidal foam/gel/film/cream/suppository)
- Documented tubal ligation (a female sterilization). In addition, a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository) should also be used
- Double barrier method: Condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository
- Any other contraceptive method with a documented failure rate of <1% per year
- Abstinence when this is in the line with the preferred and usual lifestyle of the patient.
? Male patients must use two partner of childbearing potential who agrees to use a highly effective methods (one for the patient and one for the partner) of medically method of contraception and an acceptable forms of contraception during the study and for three months after the last treatment intake. The acceptable methods of contraception are as follows:
- Condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository;
- Surgical sterilization (vasectomy with documentation of azoospermia) and a barrier method (cond
Exclusion criteria:
1. Prior treatment with masitinib, or any other tyrosine kinase inhibitor for the treatment of malignancy, except regorafenib
2. More than 3 prior chemotherapy regimens for metastatic colorectal cancer.
3. Pregnant, intent to be pregnant, or nursing female patient
4. Patient with any chronic inflammatory bowel disease
5. Patient treated for a cancer other than colorectal cancer within five years before enrollment, with the exception of basal cell carcinoma or cervical cancer in situ
6. Patient with an hepatic involvement > 50%
7. Patient with active central nervous system (CNS) metastasis or history of CNS metastases.
8. Patient with an active infection (Human immunodeficiency virus infection and/or hepatitis B or C infection …)
9. 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 judgement of the investigator, or symptomatic hypertension
? For US only: 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).
10. Patient with a history of poor compliance or of drug/alcohol abuse, or excessive alcohol beverage consumption, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent
11. For US only: Patient presenting with at least one of the following conditions:
? Patient with co-existing dermatological disease (e.g. eczema, psoriasis) or history of skin allergy
? Patient presenting with oedemas
? Patient with chronic diarrhea


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

Health Condition(s) or Problem(s) studied

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

Metastatic colorectal cancer after 2 or 3 previous lines of treatment
MedDRA version: 19.1 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864

Intervention(s)

Product Name: masitinib 100mg
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet

Product Name: masitinib 200mg
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet

Primary Outcome(s)

Secondary Objective: • Survival rate every 6 months
• Tumor assessment
- Overall Progression Free Survival (PFS)
- PFS rate every 8 weeks
- Overall Time To Progression (TTP)
- TTP rate every 8 weeks
- Best response rate
- Objective response rate (CR + PR) and Disease control rate (CR + PR + SD) every 8 weeks
• Tumor marker: Carcino-Embryonic Antigen (CEA, ng/ml) every 8 weeks
• Quality of life assessment every 8 weeks
- ECOG Performance Status
- Quality of Life according to the EORTC QLQ-C30
- Analgesic intake
- Pain improvement (visual analog scale: VAS)
• Pharmacogenomic assessment (Relationship between genomic data and overall survival)
• Safety profile using the NCI CTCAE v4.02 classification

Timepoint(s) of evaluation of this end point: Date of documented death

Primary end point(s): Overall Survival (OS) is defined as the time from the randomization to the date of documented death

Main Objective: Overall survival (OS)

Secondary Outcome(s)

Secondary end point(s): • Survival rate is defined as the proportion of patients alive at each time point
• Overall Progression Free Survival (PFS) is defined as the time from the randomization to the date of documented progression or any cause of death during the study. Progression will be assessed by CT scan according to RECIST criteria version 1.1 as defined in Table 5
• PFS rate is defined as the proportion of patients without progression or death at each time point
• Overall Time To Progression (TTP) is defined as the time from the randomization to the date of documented progression defined according to RECIST criteria version 1.1
• TTP rate is defined as the proportion of patients without progression at each time point
• Best response is defined as best response across all time points during treatment period.
• Objective response rate (ORR) defined as the number of patients with documented partial response or complete response (CR + PR), divided by the number of patients allocated at each time point.
• Disease control rate (DCR) defined as the number of patients with documented partial response, complete response or stable disease (CR + PR + SD) defined according to RECIST criteria version 1.1, divided by the number of patients allocated at each time point
• Quality of life assessed as a change in absolute value and/or percentage between baseline and each time point for the following variables
• Safety of the study treatment assessed on occurrence of Adverse Events (AEs), intake of concomitant treatments, per-treatment arising changes in physical examination, vital signs (blood pressure, pulse rate and body temperature), ECG, chest X-ray, and clinical laboratory tests (biochemistry, haematology). Safety parameters will be graded based on NCI CTCAE v4.0 classification

Timepoint(s) of evaluation of this end point: Every 8 weeks

Secondary ID(s)

2013-000493-30-ES

AB12010

Source(s) of Monetary Support

AB Science