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Comparing Efficacy and Safety of Stivant (AryoGen Bevacizumab) Versus Avastin in Metastatic Colorectal Cancer

Primary Purpose

Metastatic Colorectal Cancer

Status
Completed
Phase
Phase 3
Locations
Iran, Islamic Republic of
Study Type
Interventional
Intervention
Bevacizumab + FOLFIRI-3
Sponsored by
AryoGen Pharmed Co.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

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
  • 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

Sites / Locations

  • Shafa Hospital
  • Shahid Beheshti Hospital
  • Saba Clinic
  • Sheikh Mofid
  • Payandeh Clinic
  • Shazad Clinic
  • Imam Reza Hospital
  • Qaem Hospital
  • Rasool Hospital
  • Razi Hospital
  • Namazi Hospital
  • Firoozgar Hospital
  • Imam Khomeini Hospital
  • Imam Reza Hospital (501 Artesh)
  • Masih Daneshvari Hospital
  • Masoud Internal Clinic
  • Safa najafi clinic
  • Shariati Hospital
  • Sina Hospital
  • Taleqani Hospital
  • Mortazavizadeh Clinic
  • Seyedshohada Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab)

Bevacizumab + FOLFIRI-3 (Roche Bevacizumab)

Arm Description

Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (AryoGen) 5 mg/kg will be administered every 2 weeks.

Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (Avastin®) 5 mg/kg will be administered every 2 weeks.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Overall Survival (OS)
Overall survival OS was defined as the time from date of randomization to date of death due to any cause
Objective Response Rate
Tumor response was defined as partial and complete responses, according to the RECIST criteria ( version 1.1). The definitions were as follows: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), decrease of at least 30% in the lesion that has the largest diameter; Objective Response Rate (ORR) = CR + PR.
Time to Treatment Failure
Time to treatment failure was 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, Death due to any cause, Discontinuation of treatment
Incidence of the Adverse Events
Safety was assessed on the basis of reports of adverse events, laboratory-test results, and vital sign measurements. Adverse events were categorized According to the Common Toxicity Criteria of the National Cancer Institute, version 5.0, in which a grade of 1 indicates mild adverse events, a grade of 2 moderate adverse events, a grade of 3 serious adverse events, and a grade of 4 life-threatening adverse events
Number of Positive Anti-drug Antibody (ADA) Samples Among Patients (Immunogenicity)
Anti-drug antibody assessment

Full Information

First Posted
September 18, 2017
Last Updated
December 30, 2020
Sponsor
AryoGen Pharmed Co.
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1. Study Identification

Unique Protocol Identification Number
NCT03288987
Brief Title
Comparing Efficacy and Safety of Stivant (AryoGen Bevacizumab) Versus Avastin in Metastatic Colorectal Cancer
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
October 4, 2016 (Actual)
Primary Completion Date
July 30, 2018 (Actual)
Study Completion Date
July 30, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AryoGen Pharmed Co.

4. Oversight

5. Study Description

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.
Detailed Description
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) 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. 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), 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, 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. The primary endpoint is progression-free survival and overall survival, Objective Response rate, time of treatment failures, adverse events and immunogenicity will be assessed as secondary outcomes.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
126 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab)
Arm Type
Experimental
Arm Description
Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (AryoGen) 5 mg/kg will be administered every 2 weeks.
Arm Title
Bevacizumab + FOLFIRI-3 (Roche Bevacizumab)
Arm Type
Active Comparator
Arm Description
Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (Avastin®) 5 mg/kg will be administered every 2 weeks.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab + FOLFIRI-3
Other Intervention Name(s)
FOLFIRI-3 = irinotecan + calcium folinate + 5-fluorouracil
Intervention Description
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.
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
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 Outcome Measure Information:
Title
Overall Survival (OS)
Description
Overall survival OS was defined as the time from date of randomization to date of death due to any cause
Time Frame
Up to 12 months
Title
Objective Response Rate
Description
Tumor response was defined as partial and complete responses, according to the RECIST criteria ( version 1.1). The definitions were as follows: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), decrease of at least 30% in the lesion that has the largest diameter; Objective Response Rate (ORR) = CR + PR.
Time Frame
Up to 12 months
Title
Time to Treatment Failure
Description
Time to treatment failure was 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, Death due to any cause, Discontinuation of treatment
Time Frame
Up to 12 months
Title
Incidence of the Adverse Events
Description
Safety was assessed on the basis of reports of adverse events, laboratory-test results, and vital sign measurements. Adverse events were categorized According to the Common Toxicity Criteria of the National Cancer Institute, version 5.0, in which a grade of 1 indicates mild adverse events, a grade of 2 moderate adverse events, a grade of 3 serious adverse events, and a grade of 4 life-threatening adverse events
Time Frame
Up to 12 months
Title
Number of Positive Anti-drug Antibody (ADA) Samples Among Patients (Immunogenicity)
Description
Anti-drug antibody assessment
Time Frame
Up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hamid Rezvani, M.D
Organizational Affiliation
Shahid Beheshti University of Medical Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shafa Hospital
City
Ahvaz
Country
Iran, Islamic Republic of
Facility Name
Shahid Beheshti Hospital
City
Hamadān
Country
Iran, Islamic Republic of
Facility Name
Saba Clinic
City
Isfahan
Country
Iran, Islamic Republic of
Facility Name
Sheikh Mofid
City
Isfahan
Country
Iran, Islamic Republic of
Facility Name
Payandeh Clinic
City
Kermanshah
Country
Iran, Islamic Republic of
Facility Name
Shazad Clinic
City
Kermanshah
Country
Iran, Islamic Republic of
Facility Name
Imam Reza Hospital
City
Mashhad
Country
Iran, Islamic Republic of
Facility Name
Qaem Hospital
City
Mashhad
Country
Iran, Islamic Republic of
Facility Name
Rasool Hospital
City
Rasht
Country
Iran, Islamic Republic of
Facility Name
Razi Hospital
City
Rasht
Country
Iran, Islamic Republic of
Facility Name
Namazi Hospital
City
Shiraz
Country
Iran, Islamic Republic of
Facility Name
Firoozgar Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Imam Khomeini Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Imam Reza Hospital (501 Artesh)
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Masih Daneshvari Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Masoud Internal Clinic
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Safa najafi clinic
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Shariati Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Sina Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Taleqani Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Mortazavizadeh Clinic
City
Yazd
Country
Iran, Islamic Republic of
Facility Name
Seyedshohada Hospital
City
Yazd
Country
Iran, Islamic Republic of

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32334845
Citation
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.
Results Reference
derived
Links:
URL
http://www.irct.ir/
Description
This protocol is registered according to program in Iran Registry of Clinical Trial (IRCT) with IRCT2015072517994N2 code
URL
http://pubmed.ncbi.nlm.nih.gov/32334845/
Description
Efficacy and Safety of Proposed Bevacizumab Biosimilar BE1040V in Patients With Metastatic Colorectal Cancer: A Phase III, Randomized, Double-blind, Noninferiority Clinical Trial

Learn more about this trial

Comparing Efficacy and Safety of Stivant (AryoGen Bevacizumab) Versus Avastin in Metastatic Colorectal Cancer

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