View older revisions Content changed at 2020-11-19, 1399/08/29

Protocol summary

Study aim
The purpose of this study was to compare the efficacy and safety of the proposed bevacizumab biosimilar to the reference product in patients with metastatic colorectal cancer mCRC
Design
This phase III, randomized, two-armed, parallel, double-blinded (patient- and assessor-blinded), active-controlled, multicenter, noninferiority study was conducted in 22 centers across nine cities of Iran. The randomization plan of the 126 patients will be carried out using an on-line system (http://www.randomization.com).
Settings and conduct
This phase III, randomized, two-armed, parallel, double-blinded (patient- and assessor-blinded), active-controlled, multicenter, noninferiority study was conducted in 22 centers across nine cities of Iran
Participants/Inclusion and exclusion criteria
According to criteria
Intervention groups
Study Drug(Arm A): FOLFIRI3 , Bevacizumab (AryoGen Pharmed) Control (Arm B): FOLFIRI3 , Bevacizumab (Avastin)
Main outcome variables
The primary endpoint was progression-free survival (PFS), which was defined as the time from the date of randomization to the first date of documented progression or death as a result of any cause.1 year after randomization

General information

Reason for update
Updating the inclusion and exclusion data, updating of centers, editing of primary and secondary outcome
Acronym
IRCT registration information
IRCT registration number: IRCT2015072517994N2
Registration date: 2016-07-28, 1395/05/07
Registration timing: prospective

Last update: 2020-11-19, 1399/08/29
Update count: 1
Registration date
2016-07-28, 1395/05/07
Registrant information
Name
Mansour Shamsipour
Name of organization / entity
Clinical Trial Center, Tehran University of Medical Sciences
Country
Iran (Islamic Republic of)
Phone
+98 21 6690 1205
Email address
shamsipour@razi.tums.ac.ir
Recruitment status
Recruitment complete
Funding source
AryoGen Pharmed Company
Expected recruitment start date
2016-08-22, 1395/06/01
Expected recruitment end date
2016-08-22, 1395/06/01
Actual recruitment start date
2016-10-04, 1395/07/13
Actual recruitment end date
2017-07-30, 1396/05/08
Trial completion date
2018-07-30, 1397/05/08
Scientific title
A Phase III, randomized, two-armed, double-blind (patient and assessor blinded), parallel active controlled non-Inferiority clinical trial to evaluate the efficacy and safety of bevacizumab(AryoGen®) plus FOLFIRI-3 in comparison with bevacizumab (Avastin®) plus FOLFIRI-3 as a first line therapy in patients with metastatic colorectal cancer (mCRC)
Public title
Evaluation the efficacy and safety of bevacizumab in comparison with bevacizumab (Avastin®) as a first line therapy in patients with metastatic colorectal cancer (mCRC)
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Inclusion criteria: Male or female aged 18-75 years at the time of signing the informed consent form, have been diagnosed as mCRC verified histologically, having one or more bi-dimensionally measurable lesions as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria, was not felt to be amenable to curative resection, with an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1, life expectancy of longer than 3 months ( clinical assessment), adequate organ and marrow function as defined below: Absolute neutrophil count (ANC) greater than/equal to 1,500/mm3; o Platelets greater than/equal to 100,000/ mm3; o Hemoglobin greater than/equal to 9 gm/dl (may be transfused to maintain or exceed this level); o Total bilirubin less than/equal to 1.5 within institutional upper limit of normal (IULN); Aspartate aminotransferase (AST or SGOT)/alanine aminotransferase (ALT or SGPT) less than/equal to 2.5 times IULN, or less than/equal to 5 times IULN if known liver metastases, may have received adjuvant therapy for primary colorectal cancer provided that at least 6 months have elapsed from the time the adjuvant therapy was concluded and recurrent disease was documented, Patients with history of hypertension must be well-controlled (blood pressure less than/equal to 150/100mmHg), on a stable regimen of anti-hypertensive therapy.
Exclusion criteria:
Exclusion criteria, Radiotherapy or surgery for mCRC less than 4 weeks before random assignment, Undergone major surgical procedures or open biopsy within 28 days before the initiation of study treatment, experienced a significant traumatic injury, within 28 days before study entry, currently using or had recently used therapeutic anticoagulants, thrombolytic therapy, chronic, daily treatment with aspirin( higher than 325 mg/daily). (Patients may have prophylactic use of low molecular weight heparin, however therapeutic use of heparin or low molecular weight heparin is not acceptable) - Proteinuria exceeding 500mg/24h - History or presence of central nervous system metastases - Female patients who are pregnant or lactating - Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab, irinotecan, 5-FU, or leucovorin - Serious non-healing wound, ulcer, or an active bone fracture - Patients with any history of another primary malignancy less than/equal to 5 years, with the exception of non-melanoma skin cancer, and carcinoma in situ of the uterine cervix. - Myocardial infarction within 6 months before of study enrollment; - History of stroke within 6 months before of study enrollment; - Unstable symptomatic arrhythmia requiring medication; - Clinically significant peripheral vascular disease; - Uncontrolled diabetes; Serious active or uncontrolled infection - 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: 126
Actual sample size reached: 126
Randomization (investigator's opinion)
Randomized
Randomization description
The randomization plan of the patients will be carried out using an on-line system (http://www.randomization.com). Using permuted block randomization (length of each block is 6) will be made, for a total of 126 patients (with 2:1 allocation ratio). Once the randomization has been made, each patient is given a code with which he will be identified 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 the first two letters of the generic name and study phase, respectively (which is BE3-) and 4 numbers (corresponding to the randomization number), e.g. ABCD001BE3-0001. The randomization number will be assigned in a consecutive way.
Blinding (investigator's opinion)
Double blinded
Blinding description
Each study's drug package for the course of a patient's treatment had a 3-digit number similar to the randomization code, so as long as the random code was unique, each patient had a unique drug package that will be completely identified with the randomized process.
Placebo
Not used
Assignment
Parallel
Other design features

Secondary Ids

1

Registry name
ClinicalTrials.gov
Secondary trial Id
NCT03288987
Registration date
2018-07-30, 1397/05/08

Ethics committees

1

Ethics committee
Name of ethics committee
Shahid Beheshti University OF Medical Sciences
Street address
Tehran,Chamran highway,Yaman street,Shahid Shahryari street,Daneshjoo blvd, Shahid Beheshti University of Medical Sciences
City
Tehran
Province
Tehran
Postal code
1985717443
Approval date
2016-06-21, 1395/04/01
Ethics committee reference number
IR.SBMU.REC.1395.4

2

Ethics committee
Name of ethics committee
Ahvaz University of Medical Sciences
Street address
Olum pezeshli Bolivar, Ahvaz University of Medical Sciences, Khuzestan Province, Ahvaz, Iran
City
Ahvaz
Province
Khouzestan
Postal code
61357-15794
Approval date
2016-08-24, 1395/06/03
Ethics committee reference number
IR.AJUMS.REC.1395.351

Health conditions studied

1

Description of health condition studied
Metastatic colorectal cancer
ICD-10 code
C18-9
ICD-10 code description
Malignant neoplasm of colon

Primary outcomes

1

Description
progression-free survival
Timepoint
1 year after randomization
Method of measurement
Method of measurement: 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: the time from date of randomization to date of death due to any cause.Overall response rate: partial and complete responses, according to the RECIST criteria.Time to treatment failure: 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.Safety: Safety will be assessed based on adverse events reports, the results of laboratory tests, vital signs and immunogenicity. All adverse events are categorized by CTCAE (v. 5.0) guideline of the American National Cancer Institute.
Timepoint
During one year after randomization
Method of measurement
time based on month, RESICT guidline

Intervention groups

1

Description
Intervention (Arm A): FOLFIRI - 3+bevacizumab(AryoGen®) FOLFIRI - 3: In this group FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2400 mg/m2), and irinotecan 100 mg/m2 over 1 hour at day 3 will administer. Drug: Bevacizumab ( AryoGen ®) 5 mg/kg will administer every 2 weeks. Initially, it will administer as a 90 min infusion. If the first infusion is well-tolerated, the second will deliver as a 60 min infusion; if the 60-min infusion is well tolerated; all subsequent infusions will deliver over 30 min
Category
Treatment - Drugs

2

Description
Active Comparator(Arm B) FOLFIRI - 3 + Bevacizumab (Avastin) FOLFIRI-3: In this group FOLFIRI-3 regimen consist of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2400 mg/m2), and irinotecan 100 mg/m2 over 1 hour at day 3 will administer. Drug: Bevacizumab (Avastin) 5 mg/kg will administer every 2 weeks. Initially it will administer as a 90 min infusion. If the first infusion is well tolerated, the second will deliver as a 60 min infusion; if the 60-min infusion is well tolerated; all subsequent infusions will deliver over 30 min
Category
Treatment - Drugs

Recruitment centers

1

Recruitment center
Name of recruitment center
Taleghani Hospital
Full name of responsible person
Dr.Hamid Rezvani
Street address
Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Daneshjoo Blvd, Yman, St., Chamran Highway, Tehran, Iran.
City
Tehran
Province
Tehran
Postal code
1985717443
Phone
+98 21 2387 1021
Email
hampegrad@gmail.com

2

Recruitment center
Name of recruitment center
Emam khomini Hospital
Full name of responsible person
Seyed Reza Safaeinodehi, Farhad Shahi
Street address
Keshavarz Blvd., Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1417613151
Phone
+98 21 6405 3334
Email
safano1339@gmail.com

3

Recruitment center
Name of recruitment center
501 Artesh Hospital
Full name of responsible person
Mohsen Rajaeinejad
Street address
Etemadzadeh St., Dr.Fatemi Ave. ,Tehran Iran.
City
Tehran
Province
Tehran
Postal code
1411718546
Phone
+98 21 8802 8350
Email
dr.mrajaeinejad@gmail.com

4

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
Province
Tehran
Postal code
2542251250
Phone
+98 21 8833 6310
Email
iravani_m@yahoo.com

5

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
Province
Tehran
Postal code
1991943484
Phone
+98 21 8879 8526
Email
safa3n@icbc.ir

6

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
Province
Tehran
Postal code
321316432
Phone
+98 21 8214 1000
Email
s_m_raz@yahoo.com

7

Recruitment center
Name of recruitment center
Sina Hospital
Full name of responsible person
Dr. Mohammad Esfandbod
Street address
Sina Hospital, Khomeini St., Tehran, Iran.
City
Tehran
Province
Tehran
Postal code
225522134
Phone
+98 21 6312 0112
Email
sfand.bod.m@gmail.com

8

Recruitment center
Name of recruitment center
Shariati Hospital
Full name of responsible person
Dr. Mohammad Vaezi, Dr. Davood Babakhani
Street address
North Kargar Avenue, Tee Jalal Al-E Ahmad, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1245124685
Phone
+98 21 8490 1000
Email
Vaezi.mohammad@yahoo.com

9

Recruitment center
Name of recruitment center
Alzahra clinic
Full name of responsible person
Abbas Hajiqolami, Ali Reza Sadeghi, Amir Abbas Nekuee, Valiollah Mehrzad, Mohsen Khani
Street address
Sheikh mofis St. Alzahra clinic, Isfahan, Iran
City
Isfahan
Province
Isfehan
Postal code
69558457
Phone
+98 31 3663 1751
Email
ali_hajigholami@yahoo.com

10

Recruitment center
Name of recruitment center
Shafa Hospital
Full name of responsible person
Mohammad Seghatoleslami, Mehran Hosseinzadeh, Ahmad Ahmad Zadeh
Street address
Ahvaz, Khuzestan, Iran
City
Ahvaz
Province
Khouzestan
Postal code
6184558595
Phone
+98 61 3374 3281
Email
hoseinzadehmehran@gmail.com

11

Recruitment center
Name of recruitment center
Namazi Hospital
Full name of responsible person
Mani Ramzi, Alireza Rezvani
Street address
Zand Street, Namaz Square, Shiraz, Fars, Iran
City
Shiraz
Province
Fars
Postal code
7144556542
Phone
+98 71 3647 4332
Email
Ramzim@sums.ac.ir

12

Recruitment center
Name of recruitment center
Taleghani Hospital
Full name of responsible person
Mehrdad Payandeh, Babak Shazad
Street address
Martyr Beheshti Blvd., Kermanshah, Iran
City
Kermanshah
Province
Kermanshah
Postal code
8322352614
Phone
+98 83 3722 1814
Email
md.payande@yahoo.com

13

Recruitment center
Name of recruitment center
Emam Reza Hospital
Full name of responsible person
Abolghasem Allahyari
Street address
Emam Reza Square, Ebne Sina Avenue, Mashhad, Iran
City
Mashhad
Province
Razavi Khorasan
Postal code
5542125469
Phone
+98 51 3802 2000
Email
allahyari.abolghasem@yahoo.com

14

Recruitment center
Name of recruitment center
Ghaem Hospital
Full name of responsible person
Hossein Rahimi
Street address
Ghaem Hospital, Parastar Street, Ahmad Abad Street
City
Mashhad
Province
Razavi Khorasan
Postal code
551524212
Phone
+98 51 3802 2000
Email
dr_rahimi49@yahoo.com

15

Recruitment center
Name of recruitment center
Mortazavi Zade Clinic
Full name of responsible person
Mohammad Reza Mortazavi Zade
Street address
25, haj mohammadi ave., yazd
City
Yazd
Province
Yazd
Postal code
3533621568
Phone
+98 35 3400 4412
Fax
Email
mortazavizadeh@yahoo.com

16

Recruitment center
Name of recruitment center
Seyedshohada Hospital
Full name of responsible person
Mohammad Reza Vahidfar
Street address
Imam St., Yazd
City
Yazd
Province
Yazd
Postal code
3352633621
Phone
+98 21 5580 1630
Email
vahidfar50@yahoo.com

17

Recruitment center
Name of recruitment center
Razi Hospital
Full name of responsible person
Behrooz Najafi, Siroos Qarib, Hossein Mirpoor
Street address
Sardar jangal, Rasht, Iran
City
Rasht
Province
Guilan
Postal code
3325216425
Phone
+98 13 3355 0028
Email
Bnajafi@gums.ac.ir

18

Recruitment center
Name of recruitment center
Hazrate Rasool
Full name of responsible person
Mahdi Mirbolouk
Street address
Imam khomeinim Blvd, Rasht, Iran
City
Rasht
Province
Guilan
Postal code
3368974578
Phone
+98 13 3366 2217
Email
mirboloukmahdi@yahoo.com

19

Recruitment center
Name of recruitment center
Masih Daneshvari Hospital
Full name of responsible person
Dr Adnan Khosravi
Street address
Tehran Province, Darabad
City
tehran
Postal code
195561541
Phone
Email
adkhosravi@yahoo.com

20

Recruitment center
Name of recruitment center
Saba clinic
Full name of responsible person
Dr Mohsen Khani
Street address
amadgah Street, Isfahan
City
Isfehan
Province
Isfehan
Postal code
323555447
Phone
+98 31 3224 0219
Email
khani.hot@gmail.com

21

Recruitment center
Name of recruitment center
Shahid Beheshti
Full name of responsible person
Dr Mohammad Abbasi
Street address
qaem squ., eram bolivar Hamadan
City
hamadan
Province
Hamadan
Postal code
9888574525
Phone
+98 81 3838 0283
Email
abbasi.m@gmail.com

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Aryogene pharmed company
Full name of responsible person
Dr. Nasim Anjidani
Street address
Aryogen Biopharma 140 Corner Tajbakhsh street, 24th km Makhsous Road, Teheran, Iran
City
karaj
Province
Alborz
Postal code
3164819711
Phone
+98 26 3610 6480
Email
contact@aryogen.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Aryogene pharmed company
Proportion provided by this source
100
Public or private sector
Private
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Industry

Person responsible for general inquiries

Contact
Name of organization / entity
Aryogen pharmed company
Full name of responsible person
Dr. Nasim Anjidani
Position
Pharmacist
Latest degree
Medical doctor
Other areas of specialty/work
Street address
No 42, Attar Aqu., Vanak squ., Tehran, Iran
City
tehran
Province
Tehran
Postal code
1994766411
Phone
+98 21 4347 3000
Fax
Email
anjidani.n@orchidpharmed.com
Web page address

Person responsible for scientific inquiries

Contact
Name of organization / entity
Taleghani Hospital
Full name of responsible person
Dr.Hamid Rezvani
Position
MD, Hematoncologist
Latest degree
Medical doctor
Other areas of specialty/work
Street address
Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Daneshjoo Blvd, Yman, St., Chamran Highway, Tehran, Iran.
City
Tehran
Province
Tehran
Postal code
1985711151
Phone
+98 21230311
Fax
Email
Amini.S@orchidpharmed.com
Web page address

Person responsible for updating data

Contact
Name of organization / entity
Aryogene pharmed company
Full name of responsible person
Dr Nasim Anjidani
Position
Pharmacist
Latest degree
Medical doctor
Other areas of specialty/work
Street address
No 42, Attar Squ., Vanak Squ., Tehran Iran
City
Tehran
Province
Tehran
Postal code
1994766411
Phone
+98 21 4347 3000
Fax
Email
anjidani.n@orchidpharmed.com
Web page address

Sharing plan

Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available
Loading...