Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Clinical Trial to Evaluate the Efficacy and Safety of Bevacizumab (AryoGen Pharmed) Compared With Bevacizumab (Avastin®) in Metastatic Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03288987
Recruitment Status : Completed
First Posted : September 20, 2017
Last Update Posted : February 6, 2019
Sponsor:
Information provided by (Responsible Party):
AryoGen Pharmed Co.

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.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: Bevacizumab + FOLFIRI-3 Phase 3

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 126 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Two-armed, Double-blind (Patient and Assessors), Parallel Active Controlled Non-Inferiority Clinical Trial 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)
Actual Study Start Date : October 5, 2016
Actual Primary Completion Date : July 30, 2018
Actual Study Completion Date : July 30, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab)
Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (AryoGen) 5 mg/kg will be administered every 2 weeks.
Drug: Bevacizumab + FOLFIRI-3
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.
Other Name: FOLFIRI-3 = irinotecan + calcium folinate + 5-fluorouracil

Active Comparator: Bevacizumab + FOLFIRI-3 (Roche Bevacizumab)
Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (Avastin®) 5 mg/kg will be administered every 2 weeks.
Drug: Bevacizumab + FOLFIRI-3
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.
Other Name: FOLFIRI-3 = irinotecan + calcium folinate + 5-fluorouracil




Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ 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 ]
    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 :
  1. Overall Survival (OS) [ Time Frame: 1 Year after study start ]
    Overall survival OS is defines as the time from date of randomization to date of death due to any cause

  2. Objective Response rate [ Time Frame: 1 Year after study start ]
    Tumor response was defined as partial and complete responses, according to the RECIST criteria

  3. Time of treatment failures [ Time Frame: 1 Year after study start ]

    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. Adverse event [ Time Frame: 1 Year after study start ]
    Safety wills assess 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 4.0, 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

  5. immunogenicity [ Time Frame: 1 Year after study start ]
    antidrug antibody and neutralizing antibody assessment



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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;
    • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03288987


Locations
Layout table for location information
Iran, Islamic Republic of
Taleqani Hospital
Tehrān, Tehran, Iran, Islamic Republic of
Sponsors and Collaborators
AryoGen Pharmed Co.

Additional Information:
Layout table for additonal information
Responsible Party: AryoGen Pharmed Co.
ClinicalTrials.gov Identifier: NCT03288987     History of Changes
Other Study ID Numbers: BEV.ARY.HR.94 (III)
First Posted: September 20, 2017    Key Record Dates
Last Update Posted: February 6, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
Layout table for MeSH terms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Irinotecan
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action