Bioequivalence Study Bevacizumab Biosimilar (BEVZ92) Versus Bevacizumab (AVASTIN®) in First-line Treatment mCRC Patients

Open Label Randomized Bioequivalence Study to Evaluate the Pharmacokinetic and Safety Profile of Bevacizumab Biosimilar (BEVZ92) vs Bevacizumab (AVASTIN®), Both With FOLFOX or FOLFIRI, in First-line Treatment for mCRC Patients

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.

Planned enrolment duration: 12 months. Pre-treatment period (included in enrolment period): 1 month. Treatment period: Patients will continue treatment until disease progression or unacceptable toxicity, or withdrawal of consent.

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.