Study to evaluate 2 types of treatment (masitinib + FOLFIRI or placebo + FOLFIRI) in the treatment of patients with metastatic colorectal cancer that have received 1 previous therapy

• Register: EUCTR
• Last refreshed on: 10 December 2018
• Main ID: EUCTR2013-000490-79-CZ
• Date of registration: 28/05/2014
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: Study to evaluate 2 types of treatment (masitinib + FOLFIRI or placebo + FOLFIRI) in the treatment of patients with metastatic colorectal cancer that have received 1 previous therapy
• Scientific title: A prospective, multicenter, randomized, double blind, placebo-controlled, 2-parallel groups, phase 3 study to compare the efficacy and safety of masitinib in combination with FOLFIRI (irinotecan, 5-fluorouracil and folinic acid) to placebo in combination with FOLFIRI in second line treatment of patients with metastatic colorectal cancer
• Date of first enrolment: 22/09/2014
• Target sample size: 574
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000490-79
• 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: If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Austria, Canada, China, Cyprus, Czech Republic, France, Germany, Greece, Hong Kong, Hungary, India, Italy, Korea, Democratic People's Republic of, Korea, Republic of, Malaysia, Mexico, Morocco, Myanmar, Peru, Philippines, Romania, Russian Federation, Serbia, Singapore, Slovakia, South Africa, Spain, Taiwan, Tunisia, Ukraine, United Kingdom, United States

Contacts

• Name: Alain Moussy
• Affiliation: AB Science

• Name: Alain Moussy
• Affiliation: AB Science

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patient with non-resectable metastatic colorectal cancer with histological or cytological documentation of adenocarcinoma of the colon or rectum
2. Metastatic disease not amenable to surgical resection with curative intent
3. Patient in second line treatment after progression according to RECIST criteria following administration of a standard chemotherapy regimen for treatment of metastatic disease
4. 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
5. Patient eligible for a standard second line therapy with FOLFIRI
6. Patient with ECOG = 2
7. 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 = 1.5 x ULN (= 3 x ULN in case of liver metastasis)
• 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
8. Patient with life expectancy > 3 months
9. Female or male patient = 18 years
10. Patient weight > 40 kg and BMI > 18 kg/m2
11. Contraception
• Female patient of childbearing potential (entering the study after a menstrual period and who have a negative pregnancy test), who agrees to use two highly effective 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. 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] used with spermicidal foam/gel/film/cream/suppository)
- Documented tubal ligation (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 line with the preferred and usual lifestyle of the patient.
• Male patients must use two highly effective 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.
12. Female patient of childbearing potential must have a negative pregnancy test at screening and baseline
13. Patient able and willing to comply with study visits and procedures as per protocol
14. 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.
15. Patient able to understand the patient card and
Exclusion criteria:
1. Patient intolerant to one of these treatments: irinotecan, 5-fluorouracil (5-FU), folinic acid
2. More than 1 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 required to receive other therapy than FOLFIRI for second line metastatic colorectal cancer
7. Patient with an hepatic involvement > 50%
8. Patient with active central nervous system (CNS) metastasis or history of CNS metastases
9. Patient with an active infection (Human immunodeficiency virus infection and/or hepatitis B or C infection …)
10. 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
11. 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
WASH OUT
12. Any previous treatment with an investigational agent or chemotherapy or biological agent will require a wash-out period of four weeks prior to baseline.




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

Health Condition(s) or Problem(s) studied

Metastatic colorectal cancer after 1 previous line of treatment
MedDRA version: 20.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864

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

Intervention(s)

Product Name: masitinib 100mg
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: masitinib 200mg
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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

Secondary Objective: 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
• Quality of life assessment at week every 8 weeks
- ECOG Performance Status
- Quality of Life according to the EORTC QLQ-C30
- Analgesic intake
- Pain improvement (VAS)
• Pharmacogenomic assessment (Relationship between genomic data and overall survival)
• Safety profile using the NCI CTCAE v4.03 classification

Main Objective: Overall survival (OS)

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

Secondary Outcome(s)

Secondary end point(s): • Survival rate is defined as the rate of patients alive at each time point
• Overall Progression Free Survival (PFS) is defined as the delay between the date of 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 rate of patients without progression or death at each time point
• Overall Time To Progression (TTP) is defined as the time from the date of randomization to the date of documented progression defined according to RECIST criteria version 1.1
• TTP rate is defined as the rate of patients without documented progression at each time point
• Best Response is defined as the best response (CR or PR or SD or PD) defined according to to RECIST criteria version 1.1 recorded from the start of the treatment until end of study.
• Best Response rate is defined as the number of patients achieving the Best Response divided by the total number of patients in the population of analysis.
• Objective response rate (CR + PR) is defined as the number of patients with documented partial response or complete response defined according to RECIST, divided by the number of randomized patients
• Disease control rate (CR + PR + SD) is defined as the number of patients with documented partial response, complete response or stable disease defined according to RECIST criteria version 1.1, divided by the number of patients randomized at each time point.

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

Secondary ID(s)

2013-000490-79-GR

AB12006

Source(s) of Monetary Support

AB Science