Comparing Efficacy and Safety of Stivant (AryoGen Bevacizumab) Versus Avastin in Metastatic Colorectal Cancer
A Phase III, Randomized, Two-armed, Triple Blinded, Parallel, Active Controlled Non-Inferiority Clinical Trial of Stivant (AryoGen Trastuzumab) Efficacy and Safety in Comparison to Avastin in Metastatic Colorectal Cancer
1 other identifier
interventional
126
1 country
22
Brief Summary
This is a Phase III, randomized, two arms, double-blind (patient and assessor blinded), parallel active non inferiority controlled clinical trial with a 2:1 allocation. This trial was conducted to evaluate the efficacy and safety of bevacizumab (produced by AryoGen Pharmed) plus FOLFIRI-3 compared with bevacizumab (Avastin®) plus FOLFIRI-3 in patients with metastatic colorectal cancer (mCRC). Patients who met the following criteria could be recruited to receive the mentioned intervention randomly. Inclusion criteria: male or female aged 18-75 years, 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 (ECOG) performance status of ≤ 1, Life expectancy of longer than 3 months, Adequate organ and marrow function, 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Oct 2016
22 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 4, 2016
CompletedFirst Submitted
Initial submission to the registry
September 18, 2017
CompletedFirst Posted
Study publicly available on registry
September 20, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 30, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
July 30, 2018
CompletedResults Posted
Study results publicly available
January 22, 2021
CompletedJanuary 22, 2021
September 1, 2020
1.8 years
September 18, 2017
September 15, 2020
December 30, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS)
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.
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 12 months
Secondary Outcomes (5)
Overall Survival (OS)
Up to 12 months
Objective Response Rate
Up to 12 months
Time to Treatment Failure
Up to 12 months
Incidence of the Adverse Events
Up to 12 months
Number of Positive Anti-drug Antibody (ADA) Samples Among Patients (Immunogenicity)
Up to 12 months
Study Arms (2)
Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab)
EXPERIMENTALBevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (AryoGen) 5 mg/kg will be administered every 2 weeks.
Bevacizumab + FOLFIRI-3 (Roche Bevacizumab)
ACTIVE COMPARATORBevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (Avastin®) 5 mg/kg will be administered every 2 weeks.
Interventions
Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. 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 (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.
Eligibility Criteria
You may qualify if:
- Are 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;
- Platelets greater than/equal to 100,000/ mm3;
- Hemoglobin greater than/equal to 9 gm/dl (may be transfused to maintain or exceed this level);
- 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 150/100), on a stable regimen of anti-hypertensive therapy.
You may not qualify if:
- 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
- Myocardial infarction within 6 months before of study enrollment;
- History of stroke within 6 months before of study enrollment;
- Clinically significant peripheral vascular disease;
- Uncontrolled diabetes; Serious active or uncontrolled infection
- Inability to comply with study and/or follow-up procedures
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (22)
Shafa Hospital
Ahvāz, Iran
Shahid Beheshti Hospital
Hamadan, Iran
Saba Clinic
Isfahan, Iran
Sheikh Mofid
Isfahan, Iran
Payandeh Clinic
Kermanshah, Iran
Shazad Clinic
Kermanshah, Iran
Imam Reza Hospital
Mashhad, Iran
Qaem Hospital
Mashhad, Iran
Rasool Hospital
Rasht, Iran
Razi Hospital
Rasht, Iran
Namazi Hospital
Shiraz, Iran
Firoozgar Hospital
Tehran, Iran
Imam Khomeini Hospital
Tehran, Iran
Imam Reza Hospital (501 Artesh)
Tehran, Iran
Masih Daneshvari Hospital
Tehran, Iran
Masoud Internal Clinic
Tehran, Iran
Safa najafi clinic
Tehran, Iran
Shariati Hospital
Tehran, Iran
Sina Hospital
Tehran, Iran
Taleqani Hospital
Tehran, Iran
Mortazavizadeh Clinic
Yazd, Iran
Seyedshohada Hospital
Yazd, Iran
Related Publications (1)
Rezvani H, Mortazavizadeh SM, Allahyari A, Nekuee A, Najafi SN, Vahidfar M, Ghadyani M, Khosravi A, Qarib S, Sadeghi A, Esfandbod M, Rajaeinejad M, Rezvani A, Hajiqolami A, Payandeh M, Shazad B, Anjidani N, Meskinimood S, Alikhasi A, Karbalaeian M, Salari S. Efficacy and Safety of Proposed Bevacizumab Biosimilar BE1040V in Patients With Metastatic Colorectal Cancer: A Phase III, Randomized, Double-blind, Noninferiority Clinical Trial. Clin Ther. 2020 May;42(5):848-859. doi: 10.1016/j.clinthera.2020.03.009. Epub 2020 Apr 22.
PMID: 32334845DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Nasim Anjidani (Director of Medical- Clinical Trials)
- Organization
- Aryogen
Study Officials
- PRINCIPAL INVESTIGATOR
Hamid Rezvani, M.D
Shahid Beheshti University of Medical Sciences
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 18, 2017
First Posted
September 20, 2017
Study Start
October 4, 2016
Primary Completion
July 30, 2018
Study Completion
July 30, 2018
Last Updated
January 22, 2021
Results First Posted
January 22, 2021
Record last verified: 2020-09
Data Sharing
- IPD Sharing
- Will not share