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)
A Phase III, randomized, two-armed, double-blind, parallel active controlled to evaluate the efficacy and safety of bevacizumab plus FOLFIRI-3 in comparison with (Avastin®) plus FOLFIRI-3 as a first line therapy in patients with metastatic colorectal cancer (mCRC).
Perpose: 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).
Inclusion criteria:
- Are male or female aged 18-75 years.
- 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
- May have received adjuvant therapy for primary colorectal cancer provided that at least 6 months
Exclusion criteria:
- Prior systemic therapy for mCRC
- Radiotherapy or surgery for mCRC less than 4 weeks before random assignment.
- Experienced significant traumatic injury, within 28 days before study entry
Intervention
FOLFIRI3 + Bevacizumab (AryoGen Pharmed
FOLFIRI3 + Bevacizumab (Avastin®)
The primary end point is progression-free survival.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.
General information
Acronym
IRCT registration information
IRCT registration number:IRCT2015072517994N2
Registration date:2016-07-28, 1395/05/07
Registration timing:prospective
Last update:
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
2017-08-23, 1396/06/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
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: 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: o 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); o 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; o Serum creatinine less than/equal to 1.5 times IULN Patients must have an International Normalized Ratio (INR) less than/equal to 1.5 and a Partial Thromboplastin Time (PTT) less than/equal to IULN, 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 150/100), on a stable regimen of anti-hypertensive therapy. Exclusion criteria: prior targeted therapy for mCRC, 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 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/24 h - 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 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 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 (Patients with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible); - 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
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 Sciences
Street address
Tehran,Chamran highway,Yaman street,Shahid Shahryari street,Daneshjoo blvd, Shahid Beheshti University of Medical Sciences
City
Tehran
Postal code
Approval date
2016-06-21, 1395/04/01
Ethics committee reference number
ir.sbmu.1395.4
2
Ethics committee
Name of ethics committee
Ahvaz University of Medical Sciences
Street address
City
Ahvaz
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 study start
Method of measurement
clinical report form
Secondary outcomes
1
Description
Overall survival , Objective Response rate, Time of treatment failures
Timepoint
1 year after study start
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 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 ( 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, Dr. Sina Salari, Dr. Mojtaba Ghadyani, Dr. Hamid attarian
Street address
Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Daneshjoo Blvd, Yman, St., Chamran Highway, Tehran, Iran.
City
Tehran
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
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
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
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
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
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
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
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
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
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
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
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
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