A Clinical Trial to Determine the Therapeutic Efficacy and Safety Between Cetuximab® (Produced by CinnaGen) and FOLFIRI Compared With Erbitux® (Cetuximab, Produced by Merck Company) and FOLFIRI for RAS Wild-type Metastatic Colorectal Cancer Patients
A Clinical Trial to Determine the Therapeutic Efficacy and Safety Between Cetuximab® (Produced by CinnaGen) and FOLFIRI Compared With Erbitux® (Cetuximab, Produced by Merck Company) and FOLFIRI for RAS Wild-type Metastatic Colorectal Cancer Patients
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
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.
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.