Clinical trial NCT03288987: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Lead sponsor: AryoGen Pharmed Co.
Sponsor class: INDUSTRY
First posted: 2017-09-20
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 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:
measure: Overall Survival (OS)
timeFrame: Up to 12 months
measure: Objective Response Rate
timeFrame: Up to 12 months
measure: Time to Treatment Failure
timeFrame: Up to 12 months
measure: Incidence of the Adverse Events
timeFrame: Up to 12 months
measure: Number of Positive Anti-drug Antibody (ADA) Samples Among Patients (Immunogenicity)
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Ahvaz
country: Iran, Islamic Republic of
facility: Shafa Hospital
city: Hamadān
country: Iran, Islamic Republic of
facility: Shahid Beheshti Hospital
city: Isfahan
country: Iran, Islamic Republic of
facility: Saba Clinic
city: Isfahan
country: Iran, Islamic Republic of
facility: Sheikh Mofid
city: Kermanshah
country: Iran, Islamic Republic of
facility: Payandeh Clinic
city: Kermanshah
country: Iran, Islamic Republic of
facility: Shazad Clinic
city: Mashhad
country: Iran, Islamic Republic of
facility: Imam Reza Hospital
city: Mashhad
country: Iran, Islamic Republic of
facility: Qaem Hospital
city: Rasht
country: Iran, Islamic Republic of
facility: Rasool Hospital
city: Rasht
country: Iran, Islamic Republic of
facility: Razi Hospital
city: Shiraz
country: Iran, Islamic Republic of
facility: Namazi Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Firoozgar Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Imam Khomeini Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Imam Reza Hospital (501 Artesh)
city: Tehran
country: Iran, Islamic Republic of
facility: Masih Daneshvari Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Masoud Internal Clinic
city: Tehran
country: Iran, Islamic Republic of
facility: Safa najafi clinic
city: Tehran
country: Iran, Islamic Republic of
facility: Shariati Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Sina Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Taleqani Hospital
city: Yazd
country: Iran, Islamic Republic of
facility: Mortazavizadeh Clinic
city: Yazd
country: Iran, Islamic Republic of
facility: Seyedshohada Hospital
Study officials:
affiliation: Shahid Beheshti University of Medical Sciences
name: Hamid Rezvani, M.D
role: PRINCIPAL_INVESTIGATOR
References:
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.