A Safety and Efficacy Study of Bevacizumab, Paclitaxel, Carboplatin Compared to Avastin® in Non-Small Cell Lung Cancer
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT05654454
- Lead Sponsor
- Mabscale, LLC
- Brief Summary
BEV-III/2022 is a double-blind randomized multicenter clinical trial comparing efficacy of bevacizumab (manufactured by Mabscale, LLC) and paclitaxel plus carboplatin to Avastin® and paclitaxel plus carboplatin in first-line treatment for patients with advanced (unresectable, locally advanced, recurrent or metastatic) non-squamous NSCLC. The purpose of the study is to demonstrate equivalence of efficacy and safety of bevacizumab (manufactured by Mabscale, LLC) to Avastin®. Study includes pharmacokinetics assessment.
- Detailed Description
Bevacizumab is a monoclonal antibody currently being developed by Mabscale LLC, as a proposed biosimilar to Avastin®, which is approved as first line treatment in combination with carboplatin and paclitaxel for patients with unresectable, locally advanced, recurrent or metastatic non-squamous Non-Small Cell Lung Cancer. This randomized equivalence study is designed to meet the regulatory requirement for approval of a biosimilar product.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 620
- Written informed consent
- Male and female patients at least 18 years of age
- Newly diagnosed Stage IIIB/C or IV non-small cell lung cancer (according to Revised Cancer Staging by American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) 8th edition) or recurrent non-small cell lung cancer (NSCLC)
- Histologically or cytologically confirmed diagnosis of predominately non-squamous NSCLC
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Be eligible to receive study treatment of bevacizumab, paclitaxel, and carboplatin based on local standard of care, for the treatment of advanced or metastatic non-squamous NSCLC
- Presence of at least 1 measurable tumour as defined by modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
- Neutrophils ≥ 1,5 × 10^9/L
- Platelets ≥ 100 × 10^9/L
- Haemoglobin ≥ 90 g/L
- Bilirubin level ≤ 1.5 × upper limit of normal (ULN)
- Aspartate-aminotransferase (AST) and alanine-aminotransferase (ALT) levels < 3 × ULN (< 5 × ULN for patients with liver metastases)
- Alkaline phosphatase level < 3 × ULN (< 5 × ULN for patients with liver or bone metastases)
- Known sensitizing EGFR mutations or ALK translocation positive mutations
- Evidence of a tumor that compresses or invades major blood vessels or tumor cavitation that is likely to bleed
- Major surgery 28 days before inclusion into the study
- Minor surgery 7 days before inclusion into the study
- Stage II or higher of neuropathy or ototoxicity according to Common Terminology Criteria for Adverse Events (CTCAE) v.5.0, excluding trauma
- Life expectancy less than 6 months
- Metastases to central nervous system or carcinomatous meningitis
- Pregnancy or lactation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Bevacizumab with Paclitaxel and Carboplatin Paclitaxel Patients will begin Period 1 receiving bevacizumab combination therapy (Bevacizumab 15 mg/kg IV + Paclitaxel 175 mg/m2 + IV Carboplatin AUC 6 IV) on Day 0 of Cycle 1 for up to 6 cycles of therapy. Each cycle will consist of 3 weeks (21 days ± 3 days) and a cycle will start with the administration of bevacizumab (produced by Mabscale, LLC). In Period 2, eligible patients will continue to receive bevacizumab (produced by Mabscale, LLC) every 3 weeks as monotherapy. Bevacizumab with Paclitaxel and Carboplatin Bevacizumab Patients will begin Period 1 receiving bevacizumab combination therapy (Bevacizumab 15 mg/kg IV + Paclitaxel 175 mg/m2 + IV Carboplatin AUC 6 IV) on Day 0 of Cycle 1 for up to 6 cycles of therapy. Each cycle will consist of 3 weeks (21 days ± 3 days) and a cycle will start with the administration of bevacizumab (produced by Mabscale, LLC). In Period 2, eligible patients will continue to receive bevacizumab (produced by Mabscale, LLC) every 3 weeks as monotherapy. Bevacizumab with Paclitaxel and Carboplatin Carboplatin Patients will begin Period 1 receiving bevacizumab combination therapy (Bevacizumab 15 mg/kg IV + Paclitaxel 175 mg/m2 + IV Carboplatin AUC 6 IV) on Day 0 of Cycle 1 for up to 6 cycles of therapy. Each cycle will consist of 3 weeks (21 days ± 3 days) and a cycle will start with the administration of bevacizumab (produced by Mabscale, LLC). In Period 2, eligible patients will continue to receive bevacizumab (produced by Mabscale, LLC) every 3 weeks as monotherapy. Avastin® with Paclitaxel and Carboplatin Bevacizumab Patients will begin Period 1 receiving bevacizumab combination therapy ( Avastin® 15 mg/kg IV + Paclitaxel 175 mg/m2 IV + Carboplatin AUC 6 IV) on Day 0 of Cycle 1 for up to 6 cycles of therapy. Each cycle will consist of 3 weeks (21 days ± 3 days) and a cycle will start with the administration of bevacizumab (as Avastin®). In Period 2, eligible patients will continue to receive bevacizumab (Avastin®) every 3 weeks as monotherapy. Avastin® with Paclitaxel and Carboplatin Paclitaxel Patients will begin Period 1 receiving bevacizumab combination therapy ( Avastin® 15 mg/kg IV + Paclitaxel 175 mg/m2 IV + Carboplatin AUC 6 IV) on Day 0 of Cycle 1 for up to 6 cycles of therapy. Each cycle will consist of 3 weeks (21 days ± 3 days) and a cycle will start with the administration of bevacizumab (as Avastin®). In Period 2, eligible patients will continue to receive bevacizumab (Avastin®) every 3 weeks as monotherapy. Avastin® with Paclitaxel and Carboplatin Carboplatin Patients will begin Period 1 receiving bevacizumab combination therapy ( Avastin® 15 mg/kg IV + Paclitaxel 175 mg/m2 IV + Carboplatin AUC 6 IV) on Day 0 of Cycle 1 for up to 6 cycles of therapy. Each cycle will consist of 3 weeks (21 days ± 3 days) and a cycle will start with the administration of bevacizumab (as Avastin®). In Period 2, eligible patients will continue to receive bevacizumab (Avastin®) every 3 weeks as monotherapy.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) at Week 18 18 weeks from randomisation Objective response rate was assigned for a subject if the subject displayed either complete response (CR) or partial response (PR) per RECIST version 1.1 at Week 18, as assessed by independent radiological review committee (IRC).
- Secondary Outcome Measures
Name Time Method Progression-free Survival (PFS) At week 18 and 42 from randomisation Progression-free survival was defined as the time from randomization to subsequent confirmed progression per RECIST version 1.1, or death (whichever occurred first), measured in weeks and months. For PFS assessment clinical progression (i.e., treatment discontinuation due to progression of disease) was also considered as an event.
Duration of response (DOR) 48 weeks Duration of responce was defined as the time from responce to treatment till progression or death.
Overall Survival (OS) At week 18 and 42 from randomisation Overall survival was defined as the time from randomization to subsequent death, measured in weeks and months.
Trial Locations
- Locations (28)
Smolensk oncologic dispensary
🇷🇺Smolensk, Russian Federation
Leningrad regional clinical hospital
🇷🇺Saint Petersburg, Russian Federation
Northwestern Center for Evidence-Based Medicine
🇷🇺Saint Petersburg, Russian Federation
Bashkir State Medical University
🇷🇺Ufa, Russian Federation
Kaluga Regional Clinical Oncology Dispensary
🇷🇺Kaluga, Russian Federation
Tverskoy Regional Oncological Dispensary
🇷🇺Tver, Russian Federation
Nizhny Novgorod Regional Oncology Dispensary
🇷🇺Nizhny Novgorod, Russian Federation
National Medical Oncology Research Center n.a. N.N. Blokhina
🇷🇺Moscow, Russian Federation
Smolensk Regional Clinical Hospital
🇷🇺Smolensk, Russian Federation
Arkhangelsk Clinical Oncological Dispensary
🇷🇺Arkhangel'sk, Russian Federation
Regional clinical oncological dispensary n.a.Sigal
🇷🇺Kazan', Russian Federation
State Budget Healthcare Institution Ivanovo Regional Oncology Dispensary
🇷🇺Ivanovo, Russian Federation
Burdenko Main Military Clinical Hospital
🇷🇺Moscow, Russian Federation
Hadassah Medical Moscow
🇷🇺Moscow, Russian Federation
Euromedservice medical center
🇷🇺Pushkin, Russian Federation
Murmansk Regional Clinical Hospital
🇷🇺Murmansk, Russian Federation
Omsk clinical oncologic dispensary
🇷🇺Omsk, Russian Federation
Clinical Hospital RZD-Medicine
🇷🇺Saint Petersburg, Russian Federation
Euro Cityclinic
🇷🇺Saint Petersburg, Russian Federation
Leningrad regional clinical hospital (prev.Oncological dispensary n.a.Roman)
🇷🇺Saint Petersburg, Russian Federation
National Medical Research Center of Oncology N.A. N.N. Petrov
🇷🇺Saint Petersburg, Russian Federation
Medical University "Reaviz"
🇷🇺Samara, Russian Federation
Oblastnoy Clinical Oncological Dispansery
🇷🇺Veliki Nóvgorod, Russian Federation
Regional Clinical Oncological Hospital
🇷🇺Yaroslavl, Russian Federation
Volgograd Regional Clinical Oncology Dispensary
🇷🇺Volgograd, Russian Federation
Novosibirsk oncologic dispensary
🇷🇺Novosibirsk, Russian Federation
Perm Edge Clinical Hospital
🇷🇺Perm, Russian Federation
Perm Regional Clinical Hospital
🇷🇺Perm, Russian Federation