A 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

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2015/10/006331
• Date of registration: 30-10-2015
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: A 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
• 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: 01-11-2015
• Target sample size: 550
• Recruitment status: Other (Terminated)
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=12245
• Study type: Interventional
• Study design: Randomized, Parallel Group, Placebo Controlled Trial; Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:Centralized Blinding and masking:Participant and Investigator Blinded
• Phase: Phase 3

Countries of recruitment

Canada, China, Czech Republic, France, Greece, Hong Kong, Hungary, India, Malaysia, Philippines, Romania, Singapore, Slovakia, South Africa, Spain, Taiwan, Tunisia, United Kingdom, United States of America

Contacts

• Name: Jhansi Reddy
• Affiliation: Maya Clinicals Drug Development Pvt. Ltd.

• Name: Dr Sudhir Kumar
• Affiliation: Maya Clinicals Drug Development Pvt. Ltd.

Key inclusion & exclusion criteria

Inclusion criteria: To be eligible the patient must fulfil all the following 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 ³10 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/ALT <= 3 x ULN (<= 5 x ULN in case of liver metastases)

· GammaGT <= 2.5 x ULN (<= 5 x ULN in case of liver metastases)

· Bilirubin <= 1.5 x ULN

· Normal Creatinine or if abnormal creatinine, creatinine clearance >= 50 mL/min (Cockcroft and Gault formula)

· Albumin > 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

10. Patient weight >40 kg and BMI > 18

11. 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

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 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 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.
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 metastasis or history of CNS metastases

9. Patient with an active infection (Human immunodeficiency virus infection and/or hepatitis B or C infection â?¦)

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

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Patients with metastatic colorectal cancer

Intervention(s)

Intervention1: Masitinib, FOLFIRI: Masitinib will be taken orally, daily at 6mg/kg/day. FOLFIRI will be administered every 2 weeks
Control Intervention1: Placebo, FOLFIRI: Placebo will be taken orally, daily. FOLFIRI will be administered every 2 weeks

Primary Outcome(s)

Overall Survival (OS)Timepoint: till death or last follow up

Secondary Outcome(s)

TTP rateTimepoint: every 8 weeks

Objective Response RateTimepoint: every 8 weeks

PFS rateTimepoint: every 8 weeks

Survival RateTimepoint: every 6 months

Secondary ID(s)

AB12006 ROW version N° 3.0 dated November 21, 2013

CT/21/14 - DCG(I)

Source(s) of Monetary Support

AB Science

Ethics review

Status: Approved
Approval date: 29/06/2015
Contact:

Sri Venkateshwara Hospital Ethics Committee

Status: Not Approved
Approval date:
Contact:

Amaravati ethics committee

Status: Not Approved
Approval date:
Contact:

Apple Hospital Ethics Committee

Status: Not Approved
Approval date:
Contact:

Ethics Committee, S.P Medical College and A.G Hospitals Ethics Committee

Status: Not Approved
Approval date:
Contact:

Ethics Committee, Sri Venkateswara Institute of Medical Sciences

Status: Not Approved
Approval date:
Contact:

Institute Ethics Committee, AIIMS, New Delhi

Status: Not Approved
Approval date:
Contact:

Institutional Ethics Committee, City Cancer Centre

Status: Not Approved
Approval date:
Contact:

Institutional Ethics Committee, Government Medical College, Nagpur

Status: Not Approved
Approval date:
Contact:

Institutional Ethics Committee, JIPMER

Status: Not Approved
Approval date:
Contact:

Institutional Ethics committee, Mahatma Gandhi Cancer Hospital and Research institute

Status: Not Approved
Approval date:
Contact:

Manas Hospital Ethics Committee

Status: Not Approved
Approval date:
Contact:

Medical Ethics Committee, Kidwai Memorial Institute of Oncology

Status: Not Approved
Approval date:
Contact:

MNJ Institute of Oncology & Regional Cancer Centre Ethics Committee

Results

• Date Completed: 22/03/2016