A Safety and Efficacy Study of BCD-021 With Paclitaxel and Carboplatin Compared to Avastin With Paclitaxel and Carboplatin in Non-Small Cell Lung Cancer

April 13, 2023 updated by: Biocad

International Multicenter Randomized Double Blind Phase III Trial Comparing Safety and Efficacy of BCD-021 (CJSC BIOCAD, Russia) and Paclitaxel + Carboplatin to Avastin® (F. Hoffmann-La Roche Ltd, Switzerland) and Paclitaxel + Carboplatin in Inoperable or Advanced Non-squamous Non-small-cell Lung Cancer (NSCLC) Patients

BCD-021-02 is a double-blind randomized clinical trial comparing efficacy of BCD-021 (INN: bevacizumab) and paclitaxel + carboplatin to Avastin and paclitaxel + carboplatin in inoperable or advanced non-squamous NSCLC patients with pharmacokinetics substudy. The purpose of the study is to demonstrate the non-inferiority of efficacy and safety of BCD-021 compared to Avastin. Also study includes pharmacokinetics assessment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

353

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belarus
      • Brest, Belarus
        • Brest Regional Clinical Dispensary
      • Gomel, Belarus
        • Gomel Regional Clinical Oncology Dispensary
      • Grodno, Belarus
        • Grodno Regional Clinical Hospital
      • Vitebsk, Belarus
        • Vitebsk Regional Clinical Oncology Dispensary
  • India
      • Bangalore, India, 560027
        • HCG Bangalore Institute of Oncology
      • Bangalore, India, 560054
        • M.S.Ramaiah Memorial Hospital
      • Bangalore, India, 560099
        • Narayana Hrudayalaya Hospitals
  • Russian Federation
      • Arkhangelsk, Russian Federation, 163045
        • Arkhangelsk District Clinical Oncology Dispensary
      • Chelyabinsk, Russian Federation, 454000
        • Non-governmental Healthcare Institution "Railway Clinical hospital on the Chelyabinsk Station of JSC Russian Railways"
      • Chelyabinsk, Russian Federation
        • State-financed Health Institution "Chelyabinsk Region Clinical Oncology Dispansary"
      • Kursk, Russian Federation, 305035
        • State Healthcare Facility "Kursk Regional Oncology Dispensary"
      • Moscow, Russian Federation, 115478
        • Institution of Russian Academy of Medical Sciences "Russian Cancer Research Center named after N.N. Blokhin"
      • Moscow, Russian Federation, 194044
        • Federal State Institution "Moscow Institute of Cancer Research named after P.A. Hertsen" Ministry of Health of Russian Federation
      • Moscow Region, Russian Federation, 143423
        • State Health Institution of Moscow "Moscow City Oncology Hospital #62 of Moscow Board of Health"
      • Murmansk, Russian Federation, 183047
        • Murmansk Regional Oncology Dispensary
      • Nizhny Novgorod, Russian Federation, 603006
        • Nizhny Novgorod Region State Budgetary Healthcare Facility "Clinical Diagnostics Center"
      • Nizhny Novgorod, Russian Federation
        • State Healthcare Facility "Nizhny Novgorod Regional Oncology Dispensary"
      • Novosibirsk, Russian Federation, 630047
        • City Clinical Hospital №1
      • Orel, Russian Federation, 302020
        • Regional State Health Institution "Orlov Oncology Dispansary"
      • Penza, Russian Federation, 440071
        • State Health Institution "Region Oncology Dispansary"
      • Perm, Russian Federation, 614066
        • Perm Region Oncology Dispensary
      • Rostov-on-Don, Russian Federation, 314019
        • Federal Government Budgetary Institution "Rostov Institute of Cancer Research" of Ministry of Health of Russian Federation
      • Saint Petersburg, Russian Federation, 197022
        • Saint Petersburg City Clinical Oncology Center
      • Samara, Russian Federation, 443031
        • State-financed Health Institution "Samara Region Clinical Oncology Dispansary"
      • Sochi, Russian Federation, 354057
        • Oncology Dispensary 2
      • St. Petersburg, Russian Federation, 197022
        • St. Petersburg State Medical University n.a. I. P. Pavlov
      • St. Petersburg, Russian Federation, 197758
        • St. Petersburg Research and Practice Center for Secondary Care in Oncology
      • St.Petersburg, Russian Federation, 197758
        • N.N.Petrov Oncology Research Center
      • St.Petersburg, Russian Federation
        • Russian scientific center of radiology and surgery technologies
      • St.Petersburg, Russian Federation
        • Military Medical Academy named after S.M. Kirov
      • Stavropol, Russian Federation, 355047
        • State-financed Health Institution "Stavropol Region Clinical Oncology Dispansary"
      • Volgograd, Russian Federation, 400138
        • Volgograd District Oncology Dispensary №1
      • Volgograd, Russian Federation, 404130
        • Volgograd Regional Oncology Dispensary №3
      • Voronezh, Russian Federation, 394000
        • State Health Institution "Voronezh Region Clinical Oncology Dispansary"
  • Ukraine
      • Donetsk, Ukraine
        • Donetsk City Oncology Dispensary
      • Donetsk, Ukraine
        • Donetsk Regional Antitumor Center
      • Kharkiv, Ukraine
        • Kharkiv Regional Clinical Oncology Center
      • Kryvyi Rih, Ukraine
        • Kryvyi Rih Oncology Dispensary
      • Lviv, Ukraine
        • Lviv State Regional Cancer Diagnostic and Treatment Center
      • Makiivka, Ukraine
        • City Hospital № 2
      • Poltava, Ukraine
        • Poltava Regional Clinical Oncology Dispensary
      • Uzhhorod, Ukraine
        • Zakarpatskyi Clinical Oncology Dispensary
      • Vinnytsia, Ukraine
        • Vinnytsia Regional Clinical Oncology Dispensary
      • Zaporizhia, Ukraine
        • Zaporizhia Regional Clinical Oncology Dispensary

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Written informed consent;
  • Newly diagnosed histologically or cytologically confirmed NSCLC excluding squamous NSCLC (mixed cancer types should be classified according to the prevalent cell type);
  • IIIb or IV stage of NSCLC (TNM classification version 6);
  • Age ≥ 18 years and age ≤ 75 years (both inclusive);
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2, (not declining within 2 weeks prior to the first dose of investigational product);
  • Life expectancy - 12 weeks or more from the moment of randomization;
  • Presence of at least 1 measurable tumour with a size not less than 1 cm (revealed with CT slice thickness not more than 5 mm), as defined by modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria (specifically, no ascites, pleural, or pericardial effusions, osteoblastic bone metastases, or carcinomatous lymphangitis of the lung as only lesion;
  • Patients should be able to follow the Protocol procedures (according to Investigator's assessment);
  • Patients must implement reliable contraceptive measures during all the study treatment, starting 4 weeks prior to the administration of the first dose of investigational product until 6 months after the last dose of investigational product. This requirement does not apply to participants who have undergone surgical sterilization, or patients who are postmenopausal (documented) for the past 2 years. Reliable contraceptive measures include two methods of contraception, including one barrier method

Exclusion Criteria:

  • Squamous NSCLC;
  • Proven coagulopathy, clinically significant hemorrhage in the past including nasal hemorrhage;
  • absolute neutrophil count <1500/mm3;
  • Platelets <100 000/mm3;
  • Hemoglobin < 90 g/L;
  • Creatinine level ≥1.5 mg/dL;
  • Bilirubin level ≥1.5 × upper limit of normal (ULN);
  • Aspartate-aminotransferase(AST) and alanine-aminotransferase (ALT) levels ≥2.5 × ULN (≥5 × ULN for patients with liver metastases);
  • Alkaline phosphatase level ≥5 × ULN;
  • Current therapeutic anticoagulation treatment, aspirin (more than 325 mg/day), nonsteroidal anti-inflammatory drugs, antiplatelet agents or protracted treatment with these drugs less than 1 month before entering the study;
  • Uncontrolled hypertension comprising all cases of arterial hypertension when no decrease in blood pressure could be achieved despite treatment with a combination of 3 antihypertensive drugs including one diuretic and non-medical correction methods (low salt diet, physical exercise);
  • Any previous anticancer therapy (chemotherapy, radiation therapy , surgery etc.) of metastatic NSCLC;
  • Radiation or hormone therapy within 21 days prior to randomization;
  • Major surgery 28 days before inclusion into the study;
  • Previous antiangiogenic therapy;
  • Hypersensitivity to taxanes, platinum agents, recombinant murine proteins, contrast agents, premedication agents specified by Protocol (dexamethasone, diphenhydramine, ranitidine) or excipients of investigational products;
  • NSCLC metastases in central nervous system excluding metastases non-progressing without glucocorticosteroids within 4 weeks before inclusion into the trial;
  • Cardiovascular system pathology (CHF stage III-IV according to New York Heart Association (NYHA) classification);
  • Pregnancy or lactation;
  • Conditions limiting patient's adherence to Protocol requirements (dementia, neurologic or psychiatric disorders, drug addiction, alcoholism and others);
  • Stage II-IV neuropathy according to Common Terminology Criteria for Adverse Events (CTCAE) v.4.0;
  • Simultaneous participation in other clinical trials, previous participation in other clinical trials within 30 days before entering into the trial, previous participation in the same trial;
  • Any other concomitant cancer revealed within 5 years prior to screening, except curatively treated intraductal carcinoma in situ, curatively treated cervical carcinoma in situ or curatively treated basal cell or squamous cell carcinoma;
  • Acute or active chronic infections;
  • Hepatitis C virus, hepatitis B virus, HIV, or syphilis infections;
  • Obstacles in intravenous administration of study drugs

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BCD-021 (CISC BIOCAD)
BCD-021 is a product code for bevacizumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-021 in combination with carboplatin and paclitaxel. BCD-021 will be administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks (on Day 1 of each course). Paclitaxel will be administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.
Drug: Bevacizumab
Patients will receive 6 courses of bevacizumab in combination with carboplatin and paclitaxel. Bevacizumab will be administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks (on Day 1 of each cycle).
Other Names:
  • Avastin
  • BCD-021
Drug: Paclitaxel
Paclitaxel will be administered at a dose of 175 mg/m2 as 3 hour intravenous infusion on Day 1 of each 3-week course (6 courses totally)
Other Names:
  • Taxacad
Drug: Carboplatin
Carboplatin will be administered (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel on Day 1 of each 3-week course (6 courses totally).
Active Comparator: Avastin (F. Hoffmann-La Roche Ltd)
In this arm patients will receive 6 courses of treatment with Avastin in combination with carboplatin and paclitaxel. Avastin will be administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks on Day 1. Paclitaxel will be administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.
Drug: Bevacizumab
Patients will receive 6 courses of bevacizumab in combination with carboplatin and paclitaxel. Bevacizumab will be administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks (on Day 1 of each cycle).
Other Names:
  • Avastin
  • BCD-021
Drug: Paclitaxel
Paclitaxel will be administered at a dose of 175 mg/m2 as 3 hour intravenous infusion on Day 1 of each 3-week course (6 courses totally)
Other Names:
  • Taxacad
Drug: Carboplatin
Carboplatin will be administered (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel on Day 1 of each 3-week course (6 courses totally).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate
Time Frame: Day 127
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Day 127
Area Under the Curve After the First Test Drug Administration
Time Frame: up to Day 22, after the first bevacizumab administration (time points for blood samples: 0 h 1.5 h, 3 h, 4.5 h, 6 h, 24 h, 96 h, 168 h, 336 h and 504 h)
primary outcome measure for pharmacokinetics (PK) substudy
up to Day 22, after the first bevacizumab administration (time points for blood samples: 0 h 1.5 h, 3 h, 4.5 h, 6 h, 24 h, 96 h, 168 h, 336 h and 504 h)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Response Rate
Time Frame: Day 127
secondary outcome measure for efficacy evaluation
Day 127
Partial Response Rate
Time Frame: Day 127
secondary outcome measure for efficacy evaluation
Day 127
Stabilization Rate
Time Frame: Day 127
secondary outcome measure for efficacy evaluation
Day 127
Progression Rate
Time Frame: Day 127
secondary outcome measure for efficacy evaluation
Day 127
Occurrence of Anti-bevacizumab Antibodies
Time Frame: Day 1 (before the drug administration), Day 15, 64 and 127
Secondary outcome measure for immunogenicity assessment
Day 1 (before the drug administration), Day 15, 64 and 127

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Biocad

Investigators

  • Study Director: Yulia Linkova, MD, PhD, Director of Clinical Development Department, BIOCAD

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2012

Primary Completion (Actual)

November 1, 2014

Study Completion (Actual)

November 1, 2014

Study Registration Dates

First Submitted

December 27, 2012

First Submitted That Met QC Criteria

January 7, 2013

First Posted (Estimated)

January 9, 2013

Study Record Updates

Last Update Posted (Estimated)

January 11, 2024

Last Update Submitted That Met QC Criteria

April 13, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BCD-021-02

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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