Comparing Efficacy and Safety of Stivant (AryoGen Bevacizumab) Versus Avastin in Metastatic Colorectal Cancer
- Registration Number
- NCT03288987
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 126
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Are male or female aged 18-75 years at the time of signing the informed consent form.
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Have been diagnosed as mCRC verified histologically
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Having one or more bi-dimensionally measurable lesions as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria,
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Was not felt to be amenable to curative resection,
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With an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
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Life expectancy of longer than 3 months ( clinical assessment)
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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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) Bevacizumab + FOLFIRI-3 Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (AryoGen) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) Bevacizumab + FOLFIRI-3 Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (Avastin®) 5 mg/kg will be administered every 2 weeks.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) 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
Name Time Method Incidence of the Adverse Events Up to 12 months 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
Overall Survival (OS) Up to 12 months Overall survival OS was defined as the time from date of randomization to date of death due to any cause
Time to Treatment Failure Up to 12 months 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 treatmentObjective Response Rate Up to 12 months 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.
Number of Positive Anti-drug Antibody (ADA) Samples Among Patients (Immunogenicity) Up to 12 months Anti-drug antibody assessment
Trial Locations
- Locations (22)
Shahid Beheshti Hospital
🇮🇷Hamadān, Iran, Islamic Republic of
Masoud Internal Clinic
🇮🇷Tehran, Iran, Islamic Republic of
Safa najafi clinic
🇮🇷Tehran, Iran, Islamic Republic of
Mortazavizadeh Clinic
🇮🇷Yazd, Iran, Islamic Republic of
Qaem Hospital
🇮🇷Mashhad, Iran, Islamic Republic of
Rasool Hospital
🇮🇷Rasht, Iran, Islamic Republic of
Imam Reza Hospital (501 Artesh)
🇮🇷Tehran, Iran, Islamic Republic of
Masih Daneshvari Hospital
🇮🇷Tehran, Iran, Islamic Republic of
Firoozgar Hospital
🇮🇷Tehran, Iran, Islamic Republic of
Saba Clinic
🇮🇷Isfahan, Iran, Islamic Republic of
Imam Reza Hospital
🇮🇷Mashhad, Iran, Islamic Republic of
Imam Khomeini Hospital
🇮🇷Tehran, Iran, Islamic Republic of
Seyedshohada Hospital
🇮🇷Yazd, Iran, Islamic Republic of
Namazi Hospital
🇮🇷Shiraz, Iran, Islamic Republic of
Shariati Hospital
🇮🇷Tehran, Iran, Islamic Republic of
Sheikh Mofid
🇮🇷Isfahan, Iran, Islamic Republic of
Shazad Clinic
🇮🇷Kermanshah, Iran, Islamic Republic of
Shafa Hospital
🇮🇷Ahvaz, Iran, Islamic Republic of
Payandeh Clinic
🇮🇷Kermanshah, Iran, Islamic Republic of
Sina Hospital
🇮🇷Tehran, Iran, Islamic Republic of
Taleqani Hospital
🇮🇷Tehran, Iran, Islamic Republic of
Razi Hospital
🇮🇷Rasht, Iran, Islamic Republic of