A Phase III, randomized, two armed, parallel, double blind, active controlled, equivalency clinical trial to determine the therapeutic efficacy and safety between Cetuximab (produced by CinnaGen) and FOLFIRI compared with Erbitux® (Cetuximab, the reference drug, produced by Merck Company) and FOLFIRI as first-line treatment for RAS wild-type Metastatic Colorectal Cancer

The aim of this study is to determine the equivalency of efficacy and safety of cetuximab (CinnaGen) versus Erbitux® (Merck) in progression free survival (PFS) when added to FOLFIRI (irinotecan plus leucovorin/ 5-fluorouracil continuous infusion) in patients with metastatic colorectal cancer (mCRC) without mutations in RAS genes

A phase III, Active-controlled, Parallel, double-blind, randomized clinical trial

This is a multicenter, double-blinded study.

Inclusion: • Age of 18 years or older • Histologically confirmed adenocarcinoma of the colon or rectum • Having one or more bi-dimensionally measurable lesions as defined by RECIST Criteria • Adequate organ and marrow function Exclusion: • Previous exposure to an anti-EGFR therapy or irinotecan-based chemotherapy • Adjuvant treatment that was terminated 6 months or less before the start of treatment in our trial • The use of 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 chemically or biologically similar to Cetuximab, irinotecan, 5-FU or leucovorin. • Patients with a history of another primary malignancy in less than 5 years, • Inability to comply with study and/or follow-up procedures

Cetuximab 400 mg/m2 for the first and 250 mg/m2 for subsequent doses

Primary Endpoint: Progression Free Survival Secondary Endpoints: Overall Survival, Time to Treatment Failure, Objective Response Rate, Safety, and Immunogenicity.

updating and changing of the Colorectal metastatic cancer treatment guideline

CinnaGen Company

Eligible patients will be assigned to treatment with the use of a dynamic randomization algorithm that will be designed to achieve overall balance between groups; randomization will be stratified according to site of primary tumor and number of metastasis (1 or more than 1) with 1:2 allocation ratio. After randomization procedure, a code will be allocated to each patient that will be used as patient identifier throughout the study. The assigned code will be denoted by 4 initials (corresponding to the 2 first letter of the first name, the 2 first letter of the first surname) and 3 numbers (center code). Moreover, the code described is followed by study unique identification consisting of first three letters of the generic name (which is CET-) and 3 numbers (corresponding to the randomization number), e.g. ABCD001CET-001. The randomization number will be assigned in a consecutive way. concealment process: Randomization will not be exposed to those conducting the study and will be provided in sealed opaque envelopes with successive numbers. The original paper of randomized remains in the CRO Trial and after checking eligibility criteria, the randomization code is given to the prescriber by telephone. Randomization will not be exposed to the trial executers and will be provided to the researcher of each center in non-transparent sealed envelopes.

Both cetuximab products are indistinguishable for patients and health care providers. Since the route of administration is infusion, and the size and shape of the vial, cap, seal, aluminum and the color are quite similar, it is not possible to distinguish the type of brand from the appearance of vials and it will be possible to make patients blind about the treatment group which they have been allocated to