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
this is a Phase III, randomized, two armed, parallel, double blind (patient and assesor), active controlled, equivalency clinical trial, to compare the efficacy and safety of Cetuximab (produced by CinnaGen company) plus FOLFIRI and Erbitux® (Cetuximab, the reference drug, produced by Merck Company) plus FOLFIRI as first-line treatment for RAS wild-type Metastatic Colorectal Cancer. Patients diagnosed with RAS wild-type Metastatic Colorectal Cancer, according to RECIST criteria (Response Evaluation Criteria in Solid Tumors) and age of 18 years or older will be included. Patients with certain medical conditions such as previous exposure to an anti-EGFR therapy or irinotecan-based chemotherapy and those with adjuvant treatment that was terminated 6 months or less before the start of treatment in our trial and patients that have been treated with radiotherapy, surgery (excluding previous diagnostic biopsy), or any investigational drug in the 30-day period before the start of treatment in our trial and also female patients who are pregnant or lactating and those with history of allergic reactions attributed to compounds chemically or biologically similar to cetuximab, irinotecan, 5-FU or leucovorin and patients with a history of another primary malignancy in less than 5 years, with the exception of non-melanoma skin cancer and carcinoma in-situ of uterine cervix and also those with inability to comply with study and/or follow-up procedures are excluded. This is a randomized, double blind clinical trial in which cetuximab is administered intravenously 400 mg/m2 for the first infusion then weekly intravenous infusions of 250 mg/m2, in addition to bi-weekly Irinotecan infusion of 180 mg/m2, Folinic Acid infusion of 400 mg/m2 (racemic) or 200 mg/m2 (L-form), 5-Fluorouracil bolus of 400 mg/m2 followed by a 46-hour continuous infusion of 2400 mg/m2 until progression or unacceptable toxicity develops for 156 patients in the Cetuximab group and 78 patients in Erbitux® group over 6 months. Changes from baseline in disease activity according to WHO criteria will be assessed in 26 weeks.
The randomization plan of the patients will be carried out using an system (R-CRAN version 3.2.3). Using permuted block randomization blocks (length of each block is 2 or 4) will be made, for a total of 234 patients (with 2:1 allocation ratio).
General information
Acronym
IRCT registration information
IRCT registration number:IRCT2017110821315N10
Registration date:2017-11-15, 1396/08/24
Registration timing:prospective
Last update:
Update count:3
Registration date
2017-11-15, 1396/08/24
Registrant information
Name
Nassim Anjidani
Name of organization / entity
Orchid Pharmed
Country
Iran (Islamic Republic of)
Phone
+98 21 4347 3000
Email address
amini@orchidpharmed.com
Recruitment status
Recruitment complete
Funding source
CinnaGen Company
Expected recruitment start date
2017-11-30, 1396/09/09
Expected recruitment end date
2019-11-30, 1398/09/09
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
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
Public title
An equivalency clinical trial to determine the efficacy and safety between Cetuximab (produced by CinnaGen) compared with Erbitux® in RAS wild-type Metastatic Colorectal Cancer
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria: 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 Response Evaluation Criteria in Solid Tumors (RECIST) Criteria, metastatic disease that could not be resected for curative purposes, immunohistochemical evidence of tumor EGFR expression (expanded wild-type RAS), Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less, life expectancy of longer than 3 months (by clinical assessment), adequate organ and marrow function.
Exclusion criteria: 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, patients with history of allergic reactions attributed to compounds chemically or biologically similar to Cetuximab, irinotecan, 5-FU or leucovorin, patients with a history of another primary malignancy in less than 5 years, with the exception of non-melanoma skin cancer and carcinoma in-situ of uterine cervix, inability to comply with study and/or follow-up procedures.
Age
From 18 years old to 75 years old
Gender
Both
Phase
3
Groups that have been masked
No information
Sample size
Target sample size:
234
Randomization (investigator's opinion)
Randomized
Randomization description
Blinding (investigator's opinion)
Double blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Shahid Beheshti University of Medical Science
Street address
Tabnak St., Velenjak Region, Chamran High Way, Tehran, Iran
City
Tehran
Postal code
Approval date
2017-11-05, 1396/08/14
Ethics committee reference number
IR.SBMU.REC.1396.228
2
Ethics committee
Name of ethics committee
Tabriz University of Medical science
Street address
Tabriz University of Medical science,Tabriz
City
Tabriz
Postal code
Approval date
2017-10-15, 1396/07/23
Ethics committee reference number
IR.TABRIZ.REC.1396.603
Health conditions studied
1
Description of health condition studied
RAS wild-type Metastatic Colorectal Cancer
ICD-10 code
C18.9, C20
ICD-10 code description
Malignant neoplasm of colon, Malignant neoplasm of rectum
Primary outcomes
1
Description
Assessment of Progression-Free Survival (PFS) time of Cetuximab and Erbitux®
Timepoint
a 6-month period
Method of measurement
PFS is defined as the time from the date of randomization to the first date of documentation progression (per investigator assessment) or death as a result of any cause.
Secondary outcomes
1
Description
Overall survival
Timepoint
a 6-month period
Method of measurement
the time from date of randomization to date of death due to any cause
2
Description
Objective response rate
Timepoint
a 6-month period
Method of measurement
RECIST criteria (Response Evaluation Criteria in Solid Tumors)
3
Description
Time to treatment failure
Timepoint
a 6-month period
Method of measurement
- Time of treatment failures define 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 cell. - The tumor either became larger (disease progression) or stayed the same size after treatment, - Death from any cause - Discontinuation of treatment
4
Description
Safety and frequency of AEs
Timepoint
a 6-month period
Method of measurement
Safety wills assess on the basis of reports of adverse events, laboratory-test results, and vital sign measurements
5
Description
Immunogenicity
Timepoint
Weeks 1, 2, 4, 10, 16 and 22
Method of measurement
assessment (antidrug antibody [ADA] and neutralizing antibody [nAb])
Intervention groups
1
Description
CinnaGen Cetuximab (produced by CinnaGen) 400 mg/m2 for the first infusion, then weekly intravenous infusions of 250 mg/m2, every week for 6 months
Category
Treatment - Drugs
2
Description
Erbitux® 400 mg/m2 for the first infusion, then weekly intravenous infusions of 250 mg/m2, every week for 6 months
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Ayatollah Taleghani Hospital
Full name of responsible person
Dr. Hamid Rezvani, Dr.Sina Salari, Dr.Mojtaba Ghadyani, Dr.Hamid attarian
Street address
Tabnak St., Velenjak Region, Chamran High Way, Tehran, Iran
City
Tehran
2
Recruitment center
Name of recruitment center
Dr Safa Najfi Clinic
Full name of responsible person
Dr.Safa Najjar Najafi
Street address
Molla sadra street, Tehran, Iran
City
Tehran
3
Recruitment center
Name of recruitment center
Sheikh mofis clinic
Full name of responsible person
Dr. Fariborz Mokarian, Dr.Ali Hajiqolami,Dr. Ali Reza Sadeghi, Dr.Amir Abbas Nekuee, Dr.Valiollah Me
Street address
Sheikh mofis St. Alzahra clinic, Isfahan, Iran
City
Isfahan
4
Recruitment center
Name of recruitment center
Firozgar Hospital
Full name of responsible person
Dr. Mohsen Razavi
Street address
Valiasr Street, Valadi Street, Tehran, Iran
City
Tehran
5
Recruitment center
Name of recruitment center
Masoud clinic
Full name of responsible person
Dr. Masoud Iravani
Street address
19th street. Amirabad. Tehran Iran
City
Tehran
6
Recruitment center
Name of recruitment center
Namazee Hospital
Full name of responsible person
Dr.Mani Ramzi, Dr. Alireza Rezvani
Street address
Zand Street, Namaz Square, Shiraz, Fars, Iran
City
Shiraz
7
Recruitment center
Name of recruitment center
Dr Payandeh clinic
Full name of responsible person
Dr. Mehrdad Payandeh
Street address
Shahrdari square- Kermanshah- Iran
City
Kermanshah
8
Recruitment center
Name of recruitment center
Dr. Mortazavizadeh Clinic
Full name of responsible person
Dr. Mohammad Reza Mortazavi Zade
Street address
Yazd,Yazd province, Iran,
City
Yazd
9
Recruitment center
Name of recruitment center
Shafa Hospital
Full name of responsible person
Dr. Mehran Hosseinzadeh, Dr. Ahmad Ahmad Zadeh
Street address
Ahvaz, Khuzestan, Iran
City
Ahvaz
10
Recruitment center
Name of recruitment center
Emam Reza Hospital
Full name of responsible person
Dr. Abolghasem Allahyari
Street address
Emam Reza Square, Ebne Sina Avenue, Mashhad, Iran
City
Mashhad
11
Recruitment center
Name of recruitment center
Emam khomini Hospital
Full name of responsible person
Dr.Seyed Reza Safaeinodehi, Dr. Farhad Shahi
Street address
End of Keshavarz Blvd., Tehran, Iran
City
Tehran
12
Recruitment center
Name of recruitment center
Shohadaye Khalij Fars hospital
Full name of responsible person
Dr. Mohammad Reza Ravanbod
Street address
Bushehr University of Medical Sciences, Bushehr, Iran
City
Bushehr
13
Recruitment center
Name of recruitment center
Bahonar hospital
Full name of responsible person
Dr. Ali Nemati
Street address
Kerman street century martyr, Kerman, Iran
City
Kerman
14
Recruitment center
Name of recruitment center
Emam Reza Hospital
Full name of responsible person
Dr. Hadi Mohammad doust
Street address
North Khorasan, bojnurd
City
bojnurd
15
Recruitment center
Name of recruitment center
Shahid Ghazi hospital
Full name of responsible person
Dr Nejati, Dr Esfahani, Dr Senaat, Dr Vaez, Dr Nikanfar, Dr Eyvazi, Dr Hedayati, Dr Chavoshi, Dr Asv
Street address
Golgasht St, Daneshgah St, Tabriz
City
Tabriz
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
CinnaGen company
Full name of responsible person
Somayeh Amini
Street address
No 2, Khorasani deadend, Derakhti St, Dadman St, Shahrak-eGharb
City
Tehran
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?