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

• Register: EUCTR
• Last refreshed on: 7 January 2019
• Main ID: EUCTR2013-000493-30-ES
• Date of registration: 16/12/2014
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: Study to evaluate 3 type of treatment (masitinib + FOLFIRI, or masitinib alone, or FOLFIRI alone) 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 - Colon II
• Date of first enrolment: 03/03/2015
• Target sample size: 75
• Recruitment status: Not Recruiting
• 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

Austria, Canada, Czech Republic, France, Germany, Greece, Hungary, Italy, Romania, Slovakia, Spain, United Kingdom, United States

Contacts

• Name: Consuelo Pozo
• Affiliation: ALPHA BIORESEARCH, S.L.

• Name: Consuelo Pozo
• Affiliation: ALPHA BIORESEARCH, S.L.

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. Patient in third line or fourth line treatment for metastatic colorectal cancer
? in failure of all available therapies : 5FU, irinotecan, oxalplatin +/- bevacizumab,
? for which treatment by cetuximab or panatumumab is not recommended
? 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/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)
? Albumin > 1 x LLN
? Urea < 2 x ULN
? Proteinuria < 30 mg/dL (1+) on the dipstick. If proteinuria is ? 1+ on the dipstick, 24 hours proteinuria must be < 1.5g/24 hours
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. Man and woman of childbearing potential, who 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
10. Female patient of childbearing potential must have a negative pregnancy test at screening and baseline
11. Patient able and willing to comply with study visits and procedures as per protocol
12. 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
13. 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
14. Patient affiliated to a social security regimen
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 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

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
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
WASH-OUT
11. 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

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

Metastatic colorectal cancer after 2 or 3 previous lines of treatment
MedDRA version: 17.1 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
INN or Proposed INN: Masitinib Mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Other descriptive name: MASITINIB MESYLATE
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 100-

Product Name: masitinib 200mg
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Masitinib Mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Other descriptive name: MASITINIB MESYLATE
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 200-

Trade Name: Irinotecan (Active Sustance)
Product Name: Irinotecan
Pharmaceutical Form:
INN or Proposed INN: IRINOTECAN
CAS Number: 100286-90-6
Concentration unit: gm/m2 gram(s)/square meter
Concentration type: equal
Concentration number: 180-

Trade Name: 5-fluorouracil (active Sustance)
Product Name: 5-fluorouracil
Pharmaceutical Form:
INN or Proposed INN: FLUOROURACIL
CAS Number: 51-21-8
Other descriptive name: FLUOROURACIL
Concentration unit: gm/m2 gram(s)/square meter
Concentration type: equal
Concentration number: 2400-

Trade Name: Folinic acid (Active Sustance)
Product Name: Folinic acid
Pharmaceutical Form:
INN or Proposed INN: FOLINIC ACID
CAS Number: 1492-18-8
Other descriptive name: Calcium folinate
Concentration unit: gm/m2 gram(s)/square meter
Concentration type: equal
Concentration number: 400-

Primary Outcome(s)

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

Main Objective: Overall survival (OS)

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

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

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)

AB12010

Source(s) of Monetary Support

AB Science