Comparing Efficacy and Safety of Cetuximab (CinnaGen) Versus Erbitux® (Merck) in Metastatic Colorectal Cancer

NCT ID: NCT03391934

Last Updated: 2023-04-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 234 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-20
• Study Completion Date: 2026-02-01

Brief Summary

The study is designed as phase III, randomized, two armed, parallel, double blind (patient and assessor blinded), active controlled, and equivalency clinical trial with primary endpoint of Progression-Free Survival of Cetuximab® (produced by CinnaGen) compared with Erbitux® (Cetuximab, the reference drug) in patients with RAS wild-type Metastatic Colorectal Cancer with the allocation ratio of 2:1.Patients who met the following criteria could be recruited to receive the mentioned intervention randomly. Inclusion criteria: Male or female older than 18 years old, histologically confirmed adenocarcinoma of the colon or rectum which is metastatic, having one or more bi-dimensionally measurable lesions as defined by RECIST criteria, tumor that could not be resected for curative purposes,ECOG performance status score of 2 or less,life expectancy of longer than 3 months (clinical assessment),evidence of tumor EGFR expression (expanded wild-type RAS),adequate organ and marrow function as defined:

ANC ≥ 1,500/mm3 Plt ≥ 100,000/mm3 Hb ≥ 9 g/dL (may have had blood transfusions) AST/ALT ≤ 2.5 IULN or ≤ 5 IULN with known liver metastases Total bilirubin ≤ 1.5 IULN Serum Creatinine ≤ 1.5 IULN INR ≤ 1.5 and PTT ≤ 1.5 IULN

Detailed Description

The study is designed as phase III, randomized, two armed, parallel, double blind (patient and assessor blinded), active controlled, and equivalency clinical trial with primary endpoint of Progression-Free Survival of Cetuximab® (produced by CinnaGen) compared with Erbitux® (Cetuximab, the reference drug) in patients with RAS wild-type Metastatic Colorectal Cancer with the allocation ratio of 2:1.Patients who met the following criteria could be recruited to receive the mentioned intervention randomly. Inclusion criteria: Male or female older than 18 years old, histologically confirmed adenocarcinoma of the colon or rectum which is metastatic, having one or more bi-dimensionally measurable lesions as defined by RECIST criteria, tumor that could not be resected for curative purposes,ECOG performance status score of 2 or less,life expectancy of longer than 3 months (clinical assessment),evidence of tumor EGFR expression (expanded wild-type RAS),adequate organ and marrow function as defined:

ANC ≥ 1,500/mm3 Plt ≥ 100,000/mm3 Hb ≥ 9 g/dL (may have had blood transfusions) AST/ALT ≤ 2.5 IULN or ≤ 5 IULN with known liver metastases Total bilirubin ≤ 1.5 IULN Serum Creatinine ≤ 1.5 IULN INR ≤ 1.5 and PTT ≤ 1.5 IULN

Patients who have previous exposure to an anti-EGFR therapy or irinotecan-based chemotherapy, radiotherapy, surgery (excluding previous diagnostic biopsy), or any investigational drug in the 30-day period before the start of treatment in our trial will be excluded from the study. Also, female patients who are pregnant or lactating, and patients with any history of another primary malignancy in the past five years, with the exception of non-melanoma skin cancer, and carcinoma in situ of uterine cervix, and patients with inability to comply with the study and/or follow up procedures will be excluded.The primary endpoint of the study is Progression-Free Survival (PFS) defined as the time from randomization to disease progression or death from any cause. The secondary endpoints of the study are Overall Survival (OS) defined as the time from date of randomization to date of death due to any cause, Objective Response Rate (ORR) defined as the sum of partial and complete responses, according to RECIST criteria and Time to Treatment Failure (TTF) is defined as the time from the date of randomization to the date of each of the following:

The treatment modalities did not destroy or modify the cancer cells, The tumor either became larger (disease progression) or stayed the same size after treatment, Discontinuation of treatment, Death from any cause

Safety and Immunogenicity will also be assessed during the study.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Cetuximab+ FOLFIRI

Cetuximab (Produced by CinnaGen Co.): 400 mg/m2 weekly in the first dose and 250 mg/m2 in the next doses Irinitecan: 180 mg/m2 biweekly Leucovorin: 400 mg/m2 biweekly Fluorouracil: 400 mg/m2 push, and 2400 mg/m2 as 46-h infusion biweekly

Group Type: EXPERIMENTAL

Cetuximab + FOLFIRI

Intervention Type: DRUG

Cetuximab 400 mg/m2 will be administered in the first dose and 250 mg/m2 will be administered in the next doses every week. Irinotecan will be administered 180 mg/m2 biweekly. Leucovorin will be administered 400 mg/m2 biweekly.Fluorouracil will be administered 400 mg/m2 push, and 2400 mg/m2 as 46-h infusion biweekly.

Cetuximab + FOLFIRI

Erbitux® (Produced by Merk Co.): 400 mg/m2 weekly Irinitecan: 180 mg/m2 biweekly Leucovorin: 400 mg/m2 biweekly Fluorouracil: 400 mg/m2 push, and 2400 mg/m2 as 46-h infusion biweekly

Group Type: ACTIVE_COMPARATOR

Cetuximab + FOLFIRI

Intervention Type: DRUG

Cetuximab 400 mg/m2 will be administered in the first dose and 250 mg/m2 will be administered in the next doses every week. Irinotecan will be administered 180 mg/m2 biweekly. Leucovorin will be administered 400 mg/m2 biweekly.Fluorouracil will be administered 400 mg/m2 push, and 2400 mg/m2 as 46-h infusion biweekly.

Interventions

Cetuximab + FOLFIRI

Cetuximab 400 mg/m2 will be administered in the first dose and 250 mg/m2 will be administered in the next doses every week. Irinotecan will be administered 180 mg/m2 biweekly. Leucovorin will be administered 400 mg/m2 biweekly.Fluorouracil will be administered 400 mg/m2 push, and 2400 mg/m2 as 46-h infusion biweekly.

Intervention Type: DRUG

Other Intervention Names

FOLFIRI = irinotecan + calcium folinate + 5-fluorouracil

Eligibility Criteria

Inclusion Criteria

• Male or female older than 18 years old
• Histologically confirmed adenocarcinoma of the colon or rectum which is metastatic
• Having one or more bi-dimensionally measurable lesions as defined by RECIST criteria
• Tumor that could not be resected for curative purposes
• ECOG performance status score of 2 or less
• Life expectancy of longer than 3 months (clinical assessment)
• Evidence of tumor EGFR expression (expanded wild-type RAS)
• Adequate organ and marrow function as defined:

ANC ≥ 1,500/mm3 Plt ≥ 100,000/mm3 Hb ≥ 9 g/dL (may have had blood transfusions) AST/ALT ≤ 2.5 IULN or ≤ 5 IULN with known liver metastases Total bilirubin ≤ 1.5 IULN Serum Creatinine ≤ 1.5 IULN INR ≤ 1.5 and PTT ≤ 1.5 IULN

Exclusion Criteria

• Previous exposure to an anti-EGFR therapy or irinotecan-based chemotherapy
• Radiotherapy, surgery (excluding previous diagnostic biopsy), or any investigational drug in the 30-day period before the start of treatment in our trial
• Female patients who are pregnant or lactating
• Patients with any history of another primary malignancy in the past five years, with the exception of non-melanoma skin cancer, and carcinoma in situ of uterine cervix
• Patients with history of allergic reactions attributed to compounds of similar chemical or biologic drugs as cetuximab, irinotecan, fluorouracil or leucovorin
• Adjuvant treatment that was terminated 6 months or less before the start of treatment in our trial
• Inability to comply with study and/or follow-up procedures.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cinnagen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Taleqani Hospital

Tehran, , Iran

Site Status: RECRUITING

Countries

Iran

Central Contacts

Somayeh Amini, Pharm D

Role: CONTACT

amini.s@orchidpharmed.com

00982143473000

Facility Contacts

Somayeh Amini, Pharm D

Role: primary

amini.s@orchidpharmed.com

00982143473000

Morteza Azhdarzadeh, Pharm D

Role: backup

azhdarzadeh.m@orchidpharmed.com

00982143473000

Other Identifiers

CET.CIN.HR.96 (III)

Identifier Type: -

Identifier Source: org_study_id