Bioequivalence Study Bevacizumab Biosimilar (BEVZ92) Versus Bevacizumab (AVASTIN®) in First-line Treatment mCRC Patients
Condition: Metastatic Colorectal Cancer (mCRC)
MeSH terms: Colorectal Neoplasms
Intervention: Bevacizumab biosimilar (BEVZ92); Avastin® (bevacizumab, reference product)
Intervention description: Active ingredient Bevacizumab 25 mg/mL (strength = 100 mg/4 mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).
FOLFIRI = Folinic Acid + Fluorouracil + Irinotecan FOLFOX = Folinic Acid + Fluorouracil + Oxaliplatin Treatment will continue until disease progression, unacceptable toxicity, patient withdraws consent or death (whichever occurs first).
*The first infusion will be given over 90 minutes. If it is well tolerated, the second infusion can be given over 60 minutes. If it is well tolerated, subsequent infusions can be given over 30 minutes.
The FOLFOX (any) or FOLFIRI regimen will be chosen as per investigator's criteria based on the hospital standard of care.; Active ingredient: Bevacizumab 25 mg/mL (strength: 100 mg/4 mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to administration of chemotherapy. Treatment will continue until disease progression, unacceptable toxicity, patient withdraws consent or death (whichever occurs first).
*The first infusion will be given over 90 minutes. If the first infusion is well tolerated, the second infusion can be given over 60 minutes. If this infusion is well tolerated, subsequent infusions can be given over 30 minutes.
The FOLFOX (any) or FOLFIRI regimen will be chosen as per investigator's criteria based on the hospital standard of care.
Intervention MeSH terms: Leucovorin; Folic Acid; Bevacizumab; Fluorouracil; Oxaliplatin; Irinotecan; Levoleucovorin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 142.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: colorectal cancer; metastatic; first-line treatment; comparability

Summary:

      This is a multicenter, open label, randomized bioequivalence study of BEVZ92 (bevacizumab
      biosimilar) and Avastin® with 2 parallel arms to compare the pharmacokinetic (PK) profile of
      BEVZ92 and Avastin® in combination with FOLFOX (any) or FOLFIRI chemotherapy.

      FOLFOX (any) or FOLFIRI will be chosen as per investigator criteria based on the hospital
      standard of care.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patient must not have had prior chemotherapy for advanced or metastatic disease.
             Patients could have received adjuvant chemotherapy or adjuvant chemo-radiotherapy.

          2. Patient with mCRC for whom bio-chemotherapy is indicated.

          3. Patients must have at least one measurable non-irradiated site of disease according to
             RECIST (version 1.1) criteria. If the patient has had previous irradiation of the
             marker lesion(s), there must be evidence of progression since the radiation.

          4. Minimum of 4 weeks since any major surgery, completion of radiation, or completion of
             all prior systemic anticancer therapy

          5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

          6. Adequate bone marrow function

          7. Adequate liver function defined within specific parameters

          8. Adequate renal function defined within specific parameters

          9. Adequate coagulation parameters defined within specific parameters

         10. Negative pregnancy test for females of a childbearing potential.

         11. Use of an effective form of contraception during the study (for subjects of
             childbearing potential and their partners).

         12. Life expectation ≥ 3 months

        Exclusion Criteria:

          1. Prior treatment for advanced or metastatic colorectal cancer.

          2. Prior treatment with an anti-angiogenesis agent, in either the neoadjuvant or adjuvant
             setting.

          3. Concurrent use of investigational anti-neoplastic agents (including up to 4 weeks
             prior to enrolment).

          4. History of any other malignancy unless the malignancy is in complete remission and the
             patient has been off all therapy for that malignancy for at least 5 years.

          5. Chronic treatment with systemic steroids or other immunosuppressive agents; topical or
             inhaled corticosteroids are allowed.

          6. Scheduled immunization with attenuated live vaccines during study period or within 1
             week prior to study entry.

          7. Uncontrolled brain or lepto-meningeal metastases, including patients who continue to
             require glucocorticoids for brain or lepto-meningeal metastases.

          8. Patients with active bleeding or history of bleeding diathesis on oral anti-vitamin K
             medication (except low dose coumadin) within the past 6 month prior to randomization
             or coagulopathy.

          9. Patients with history of cerebral vascular accident, transient ischemic attack, or
             subarachnoid haemorrhage within the past 6 month prior to randomization.

         10. Patients who have any severe and/or uncontrolled medical conditions or other
             conditions that could affect their participation in the study

         11. Patients with serious non-healing wound, ulcer, bone fracture, or with a major
             surgical procedure, or significant traumatic injury within 4 weeks prior to
             randomization

         12. Patients with clinical symptoms or signs of gastrointestinal obstruction that require
             parenteral hydration and/or nutrition.

         13. Patients with history of abdominal fistula, gastrointestinal perforation, or
             intra-abdominal abscess within the past 6 months prior to randomization.

         14. Patients with history of hypersensitivity to any of the study drugs or ingredients.