Clinical trial NCT02069704: Bioequivalence Study Bevacizumab Biosimilar (BEVZ92) Versus Bevacizumab (AVASTIN®) in First-line Treatment mCRC Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Colorectal Cancer (mCRC)
Keywords: colorectal cancer
metastatic
first-line treatment
comparability
Lead sponsor: mAbxience Research S.L.
Sponsor class: INDUSTRY
Collaborators: name: Laboratorio Elea Phoenix S.A.
name: Libbs Farmacêutica LTDA
First posted: 2014-02-24
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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.

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.

Primary outcomes:
measure: Area Under the Concentration-versus-time Curve (AUC) at Cycle 1 (AUC0-336h) of BEVZ92 and Avastin®
timeFrame: AUC0-336 hrs: 0 to 336 hours after start of the first infusion
measure: AUC at Steady State (AUCss) of BEVZ92 and Avastin®
timeFrame: AUCss: 0 to 336 hours after the administration of Cycle 7 infusion (Week 13).
Secondary outcomes:
measure: Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Reported With BEVZ92 and Avastin®
timeFrame: From first study dose and up to 30 days after the end of study treatment for each patient, for an average of 11 months
measure: Anti-Drug Antibody (ADA) of BEVZ92 and Avastin®
timeFrame: At baseline, and on Day 1 (pre-dose) of Cycles: 1, 5 and 8, and 12 months after first drug administration
measure: Objective Response Rate (ORR) of BEVZ92 and Avastin®
timeFrame: Every four weeks. Up to 48 weeks
measure: Cmax,sd of BEVZ92 and Avastin®
timeFrame: Cmax, sd: 0 to 336 hours after start of the first infusion.
measure: Progression-free Survival (PFS) of BEVZ92 and Avastin®
timeFrame: 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.
measure: Cmax,ss of BEVZ92 and Avastin®
timeFrame: Cmax, ss: 0 to 336 hours post-dose after the administration of Cycle 7 infusion (Week 13)
measure: Ctrough,sd of BEVZ92 and Avastin®
timeFrame: Ctrough, sd: 0 to 336 hours after start of the first infusion.
measure: Ctrough,ss of BEVZ92 and Avastin®
timeFrame: Ctrough, ss: 0 to 336 hours after the administration of the Cycle 7 infusion.
measure: Elimination Half-life (t1/2) of BEVZ92 and Avastin®
timeFrame: t1/2: 0 to 336 hours after the administration of the Cycle 7 infusion.
measure: Elimination Rate Constant (Kel) of BEVZ92 and Avastin®
timeFrame: Kel: 0 to 336 hours after the administration of the Cycle 7 infusion.
measure: Volume of Distribution (Vd) of BEVZ92 and Avastin®
timeFrame: Vd: 0 to 336 hours after the administration of the Cycle 7 infusion.
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Hospital de Gastroenterologia "Dr. Carlos Bonorino Udaondo"
city: Rosario
country: Argentina
facility: Instituto Oncológico de Rosario
city: Barretos
country: Brazil
facility: Fundaçáo Pio XII - Hospital do Cancer de Barretos
city: Ijui
country: Brazil
facility: Hospital Caridade
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas da Pucrs
city: São Paulo
country: Brazil
facility: Centro de Pesquisa do Instituto Brasileiro de Controle do Câncer - IBCC
city: São Paulo
country: Brazil
facility: Hosp. A.C Camargo
city: São Paulo
country: Brazil
facility: Instituto do Cancer del estado de S. Paulo (ICEPS )
city: Karamsad
country: India
facility: M S Patel Cancer Centre- Shree Krishna Hospital
state: Gujarat
city: Chennai
country: India
facility: Sri Ramachandra Hospital
city: Mumbai
country: India
facility: Tata Hospital
city: Nagpur
country: India
facility: Central India Canter Research Institute
city: Nashik
country: India
facility: Curie Manavta Cancer Center
city: Thiruvananthapuram
country: India
facility: Regional Cancer Center & Medical College
city: Madrid
country: Spain
facility: Centro Oncológico Clara Campal
city: Dnipropetrovsk
country: Ukraine
facility: Dnipropetrovsk City Multiple-discipline Clinical Hospital №4
city: Kharkiv
country: Ukraine
facility: Kharkiv Regional Clinical Oncology Center
city: Lviv
country: Ukraine
facility: Danylo Halytskiy Lviv National Medical University
Study officials:
References:
citation: 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.