Clinical trial NCT03391934: Comparing Efficacy and Safety of Cetuximab (CinnaGen) Versus Erbitux® (Merck) in Metastatic Colorectal Cancer
Official title: A Phase III, Randomized, Two-armed, Parallel, Double-blind, Active-controlled, Equivalency Clinical Trial of Cetuximab (CinnaGen Co.) Efficacy and Safety Compared With Erbitux (Merck Co.) and FOLFIRI for RAS Wild-type mCRC
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Keywords: RAS Wild-type
Cetuximab
Metastatic Colorectal Cancer
Lead sponsor: Cinnagen
Sponsor class: INDUSTRY
First posted: 2018-01-05
Enrollment: 234
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: PFS was measured from the start of chemotherapy to the date of disease progression or to the date of death if no progression whichever came first, assessed up to 26 weeks
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 26 weeks after study start
measure: Objective Response rate
timeFrame: 26 weeks after study start
measure: Time of treatment failures
timeFrame: 26 weeks after study start
measure: Adverse events
timeFrame: 26 weeks after study start
measure: immunogenicity
timeFrame: 26 weeks after study start
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Taleqani Hospital
Study officials:
References: