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

NCT02069704 | Completed Phase 1 Results DMC

• 1 other identifier: BEVZ92-A-01-13
• Study Type: interventional
• Target: 142
• Locations: 5 countries
• Sites: 18

Brief 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.

Conditions

Metastatic Colorectal Cancer (mCRC)

Keywords

colorectal cancer; metastatic; first-line treatment; comparability

Outcome Measures

Primary Outcomes (2)

• Area Under the Concentration-versus-time Curve (AUC) at Cycle 1 (AUC0-336h) of BEVZ92 and Avastin®

  To compare the pharmacokinetic (PK) profile of BEVZ92 and Avastin®, both administered in combination with FOLFOX (any) or FOLFIRI, by means of comparing the truncated AUC calculated from start of the first infusion until start of the second infusion (i.e. at Cycle 1; AUC0-336h) For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) of the ratio of a log-transformed exposure measure (AUC) falls completely within the range 80-125%.

  AUC0-336 hrs: 0 to 336 hours after start of the first infusion

• AUC at Steady State (AUCss) of BEVZ92 and Avastin®

  To compare the PK profile of BEVZ92 and Avastin®, both administered in combination with FOLFOX (any) or FOLFIRI, by means of comparing the truncated area under the concentration-versus-time curve calculated over a dosage interval at steady state (i.e. at Cycle 7; AUCss). For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% CI of the ratio of a log-transformed exposure measure (AUC) falls completely within the range 80-125%.

  AUCss: 0 to 336 hours after the administration of Cycle 7 infusion (Week 13).

Secondary Outcomes (11)

• Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Reported With BEVZ92 and Avastin®

  From first study dose and up to 30 days after the end of study treatment for each patient, for an average of 11 months

• Anti-Drug Antibody (ADA) of BEVZ92 and Avastin®

  At baseline, and on Day 1 (pre-dose) of Cycles: 1, 5 and 8, and 12 months after first drug administration

• Objective Response Rate (ORR) of BEVZ92 and Avastin®

  Every four weeks. Up to 48 weeks

• Cmax,sd of BEVZ92 and Avastin®

  Cmax, sd: 0 to 336 hours after start of the first infusion.

• Progression-free Survival (PFS) of BEVZ92 and Avastin®

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 weeks.

Study Arms (2)

Bevacizumab biosimilar (BEVZ92)

EXPERIMENTAL

Bevacizumab 25 mg/mL (strength: 100 mg/4 mL).

Drug: Bevacizumab biosimilar (BEVZ92)

Avastin® (bevacizumab, ref. product)

ACTIVE COMPARATOR

Bevacizumab 25mg/ml (strength: 100mg/4ml)

Drug: Avastin® (bevacizumab, reference product)

Interventions

Bevacizumab biosimilar (BEVZ92) DRUG

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.

Also known as: FOLFOX = Folinic acid + Fluorouracil + Oxaliplatin, FOLFIRI = Folinic acid + Fluorouracil + Irinotecan

Bevacizumab biosimilar (BEVZ92)

Avastin® (bevacizumab, reference product) DRUG

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.

Also known as: FOLFOX = Folinic acid + Fluorouracil + Oxaliplatin, FOLFIRI = Folinic acid + Fluorouracil + Irinotecan

Avastin® (bevacizumab, ref. product)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must not have had prior chemotherapy for advanced or metastatic disease. Patients could have received adjuvant chemotherapy or adjuvant chemo-radiotherapy.
• Patient with mCRC for whom bio-chemotherapy is indicated.
• 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.
• Minimum of 4 weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Adequate bone marrow function
• Adequate liver function defined within specific parameters
• Adequate renal function defined within specific parameters
• Adequate coagulation parameters defined within specific parameters
• Negative pregnancy test for females of a childbearing potential.
• Use of an effective form of contraception during the study (for subjects of childbearing potential and their partners).
• Life expectation ≥ 3 months

You may not qualify if:

• Prior treatment for advanced or metastatic colorectal cancer.
• Prior treatment with an anti-angiogenesis agent, in either the neoadjuvant or adjuvant setting.
• Concurrent use of investigational anti-neoplastic agents (including up to 4 weeks prior to enrolment).
• 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.
• Chronic treatment with systemic steroids or other immunosuppressive agents; topical or inhaled corticosteroids are allowed.
• Scheduled immunization with attenuated live vaccines during study period or within 1 week prior to study entry.
• Uncontrolled brain or lepto-meningeal metastases, including patients who continue to require glucocorticoids for brain or lepto-meningeal metastases.
• 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.
• Patients with history of cerebral vascular accident, transient ischemic attack, or subarachnoid haemorrhage within the past 6 month prior to randomization.
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
• 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
• Patients with clinical symptoms or signs of gastrointestinal obstruction that require parenteral hydration and/or nutrition.
• Patients with history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months prior to randomization.
• Patients with history of hypersensitivity to any of the study drugs or ingredients.

Sponsors & Collaborators

• mAbxience Research S.L.: lead
• Laboratorio Elea Phoenix S.A.: collaborator
• Libbs Farmacêutica LTDA: collaborator

Study Sites (18)

Hospital de Gastroenterologia "Dr. Carlos Bonorino Udaondo"

Buenos Aires, Argentina

Location

Instituto Oncológico de Rosario

Rosario, Argentina

Location

Fundaçáo Pio XII - Hospital do Cancer de Barretos

Barretos, Brazil

Location

Hospital Caridade

Ijuí, Brazil

Location

Hospital Sao Lucas da Pucrs

Porto Alegre, Brazil

Location

Centro de Pesquisa do Instituto Brasileiro de Controle do Câncer - IBCC

São Paulo, Brazil

Location

Hosp. A.C Camargo

São Paulo, Brazil

Location

Instituto do Cancer del estado de S. Paulo (ICEPS )

São Paulo, Brazil

Location

M S Patel Cancer Centre- Shree Krishna Hospital

Karamsad, Gujarat, 388 325, India

Location

Sri Ramachandra Hospital

Chennai, India

Location

Tata Hospital

Mumbai, India

Location

Central India Canter Research Institute

Nagpur, India

Location

Curie Manavta Cancer Center

Nashik, India

Location

Regional Cancer Center & Medical College

Thiruvananthapuram, India

Location

Centro Oncológico Clara Campal

Madrid, Spain

Location

Dnipropetrovsk City Multiple-discipline Clinical Hospital №4

Dnipropetrovsk, Ukraine

Location

Kharkiv Regional Clinical Oncology Center

Kharkiv, Ukraine

Location

Danylo Halytskiy Lviv National Medical University

Lviv, Ukraine

Location

Related Publications (1)

• Romera A, Peredpaya S, Shparyk Y, Bondarenko I, Mendonca Bariani G, Abdalla KC, Roca E, Franke F, Melo Cruz F, Ramesh A, Ostwal V, Shah P, Rahuman SA, Paravisini A, Huerga C, Del Campo Garcia A, Millan S. Bevacizumab biosimilar BEVZ92 versus reference bevacizumab in combination with FOLFOX or FOLFIRI as first-line treatment for metastatic colorectal cancer: a multicentre, open-label, randomised controlled trial. Lancet Gastroenterol Hepatol. 2018 Dec;3(12):845-855. doi: 10.1016/S2468-1253(18)30269-3. Epub 2018 Sep 24.

  PMID: 30262136 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis

Interventions

BEVZ92; Fluorouracil; Oxaliplatin; Irinotecan; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Susana Millan
• Organization: mAbxience

susana.millan@mabxience.com

+34917711500

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2014
• First Posted: February 24, 2014
• Study Start: October 29, 2014
• Primary Completion: October 1, 2015
• Study Completion: June 1, 2017
• Last Updated: July 23, 2019
• Results First Posted: July 23, 2019

Record last verified: 2019-07

Locations

AR (2); IN (6); BR (6); ES (1); UA (3)