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IRCT2015072517994N2 IRCT 2016-07-28 Aryogene pharmed company Evaluation the efficacy and safety of bevacizumab in comparison with bevacizumab (Avastin®) as a first line therapy in patients with metastatic colorectal cancer (mCRC) A Phase III, randomized, two-armed, double-blind (patient and assessor blinded), parallel active controlled non-Inferiority clinical trial to evaluate the efficacy and safety of bevacizumab(AryoGen®) plus FOLFIRI-3 in comparison with bevacizumab (Avastin®) plus FOLFIRI-3 as a first line therapy in patients with metastatic colorectal cancer (mCRC) 2016-08-22 anticipated 126 Complete https://irct.ir/trial/16423 interventional Randomization: Randomized, Blinding: Double blinded, Placebo: Not used, Assignment: Parallel, Purpose: Treatment, Randomization description: The randomization plan of the patients will be carried out using an on-line system (http://www.randomization.com). Using permuted block randomization (length of each block is 6) will be made, for a total of 126 patients (with 2:1 allocation ratio). Once the randomization has been made, each patient is given a code with which he will be identified throughout the study. The assigned code will be denoted by 4 initials (corresponding to the 2 first letter of the first name, the 2 first letter of the first surname), and 3 numbers (center code). Moreover, the code described is followed by study unique identification consisting of the first two letters of the generic name and study phase, respectively (which is BE3-) and 4 numbers (corresponding to the randomization number), e.g. ABCD001BE3-0001. The randomization number will be assigned in a consecutive way, Blinding description: Each study's drug package for the course of a patient's treatment had a 3-digit number similar to the randomization code, so as long as the random code was unique, each patient had a unique drug package that will be completely identified with the randomized process. 3 Metastatic colorectal cancer. Intervention 1: Intervention (Arm A): FOLFIRI - 3+bevacizumab(AryoGen®) FOLFIRI - 3: In this group 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 (2400 mg/m2), and irinotecan 100 mg/m2 over 1 hour at day 3 will administer. Drug: Bevacizumab ( AryoGen ®) 5 mg/kg will administer every 2 weeks. Initially, it will administer as a 90 min infusion. If the first infusion is well-tolerated, the second will deliver as a 60 min infusion; if the 60-min infusion is well tolerated; all subsequent infusions will deliver over 30 min. Intervention 2: Active Comparator(Arm B) FOLFIRI - 3 + Bevacizumab (Avastin) FOLFIRI-3: In this group FOLFIRI-3 regimen consist 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 (2400 mg/m2), and irinotecan 100 mg/m2 over 1 hour at day 3 will administer. Drug: Bevacizumab (Avastin) 5 mg/kg will administer every 2 weeks. Initially it will administer as a 90 min infusion. If the first infusion is well tolerated, the second will deliver as a 60 min infusion; if the 60-min infusion is well tolerated; all subsequent infusions will deliver over 30 min. Undecided - It is not yet known if there will be a plan to make this available Justification or reason for indecision in sharing IPD is There is no further information
public Dr. Nasim Anjidani
No 42, Attar Aqu., Vanak squ., Tehran, Iran
tehran Iran (Islamic Republic of) 1994766411 +98 21 4347 3000 anjidani.n@orchidpharmed.com Aryogen pharmed company scientific Dr.Hamid Rezvani
Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Daneshjoo Blvd, Yman, St., Chamran Highway, Tehran, Iran.
Tehran Iran (Islamic Republic of) 1985711151 +98 21230311 Amini.S@orchidpharmed.com Taleghani Hospital Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Åland Islands Iran (Islamic Republic of) Iran (Islamic Republic of) Inclusion criteria: 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; o Platelets greater than/equal to 100,000/ mm3; o Hemoglobin greater than/equal to 9 gm/dl (may be transfused to maintain or exceed this level); o 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 150/100mmHg), on a stable regimen of anti-hypertensive therapy. 18 years 75 years Both Exclusion criteria, 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 a 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/24h - 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 an 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 the 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; - Clinically significant peripheral vascular disease; - Uncontrolled diabetes; Serious active or uncontrolled infection - Inability to comply with study and/or follow-up procedures C18-9 Malignant neoplasm of colon Treatment - Drugs Treatment - Drugs Intervention (Arm A): FOLFIRI - 3+bevacizumab(AryoGen®) FOLFIRI - 3: In this group 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 (2400 mg/m2), and irinotecan 100 mg/m2 over 1 hour at day 3 will administer. Drug: Bevacizumab ( AryoGen ®) 5 mg/kg will administer every 2 weeks. Initially, it will administer as a 90 min infusion. If the first infusion is well-tolerated, the second will deliver as a 60 min infusion; if the 60-min infusion is well tolerated; all subsequent infusions will deliver over 30 min Active Comparator(Arm B) FOLFIRI - 3 + Bevacizumab (Avastin) FOLFIRI-3: In this group FOLFIRI-3 regimen consist 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 (2400 mg/m2), and irinotecan 100 mg/m2 over 1 hour at day 3 will administer. Drug: Bevacizumab (Avastin) 5 mg/kg will administer every 2 weeks. Initially it will administer as a 90 min infusion. If the first infusion is well tolerated, the second will deliver as a 60 min infusion; if the 60-min infusion is well tolerated; all subsequent infusions will deliver over 30 min Progression-free survival. Timepoint: 1 year after randomization. Method of measurement: Method of measurement: 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. Overall survival: the time from date of randomization to date of death due to any cause.Overall response rate: partial and complete responses, according to the RECIST criteria.Time to treatment failure: 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.Safety: Safety will be assessed based on adverse events reports, the results of laboratory tests, vital signs and immunogenicity. All adverse events are categorized by CTCAE (v. 5.0) guideline of the American National Cancer Institute. Timepoint: During one year after randomization. Method of measurement: time based on month, RESICT guidline. NCT03288987 ClinicalTrials.gov Aryogene pharmed company Approved 2016-06-21 Shahid Beheshti University OF Medical Sciences Tehran,Chamran highway,Yaman street,Shahid Shahryari street,Daneshjoo blvd, Shahid Beheshti University of Medical Sciences Tehran Tehran Iran (Islamic Republic of) Approved 2016-08-24 Ahvaz University of Medical Sciences Olum pezeshli Bolivar, Ahvaz University of Medical Sciences, Khuzestan Province, Ahvaz, Iran Ahvaz Khouzestan Iran (Islamic Republic of)