Comparing Efficacy and Safety of Stivant (AryoGen Bevacizumab) Versus Avastin in Metastatic Colorectal Cancer
Condition: Metastatic Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Bevacizumab + FOLFIRI-3
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.
Intervention MeSH terms: Leucovorin; Bevacizumab; Fluorouracil; Irinotecan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 126.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

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.
    

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