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

NCT01763645 | Completed Phase 3 Results

• 1 other identifier: BCD-021-02
• Study Type: interventional
• Target: 353
• Locations: 4 countries
• Sites: 44

Brief Summary

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.

Conditions

Non-small Cell Lung Cancer

Keywords

NSCLC; bevacizumab; pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate

  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

  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 Outcomes (5)

• Complete Response Rate

  Day 127

• Partial Response Rate

  Day 127

• Stabilization Rate

  Day 127

• Progression Rate

  Day 127

• Occurrence of Anti-bevacizumab Antibodies

  Day 1 (before the drug administration), Day 15, 64 and 127

Study Arms (2)

BCD-021 (CISC BIOCAD)

EXPERIMENTAL

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; Drug: Paclitaxel; Drug: Carboplatin

Avastin (F. Hoffmann-La Roche Ltd)

ACTIVE COMPARATOR

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; Drug: Paclitaxel; Drug: Carboplatin

Interventions

Bevacizumab DRUG

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).

Also known as: Avastin, BCD-021

Avastin (F. Hoffmann-La Roche Ltd); BCD-021 (CISC BIOCAD)

Paclitaxel DRUG

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)

Also known as: Taxacad

Avastin (F. Hoffmann-La Roche Ltd); BCD-021 (CISC BIOCAD)

Carboplatin DRUG

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).

Avastin (F. Hoffmann-La Roche Ltd); BCD-021 (CISC BIOCAD)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Biocad: lead

Study Sites (44)

Brest Regional Clinical Dispensary

Brest, Belarus

Location

Grodno Regional Clinical Hospital

Grodno, Belarus

Location

Gomel Regional Clinical Oncology Dispensary

Homyel, Belarus

Location

Vitebsk Regional Clinical Oncology Dispensary

Vitebsk, Belarus

Location

HCG Bangalore Institute of Oncology

Bangalore, 560027, India

Location

M.S.Ramaiah Memorial Hospital

Bangalore, 560054, India

Location

Narayana Hrudayalaya Hospitals

Bangalore, 560099, India

Location

Arkhangelsk District Clinical Oncology Dispensary

Arkhangelsk, 163045, Russia

Location

Non-governmental Healthcare Institution "Railway Clinical hospital on the Chelyabinsk Station of JSC Russian Railways"

Chelyabinsk, 454000, Russia

Location

State-financed Health Institution "Chelyabinsk Region Clinical Oncology Dispansary"

Chelyabinsk, Russia

Location

State Healthcare Facility "Kursk Regional Oncology Dispensary"

Kursk, 305035, Russia

Location

Institution of Russian Academy of Medical Sciences "Russian Cancer Research Center named after N.N. Blokhin"

Moscow, 115478, Russia

Location

Federal State Institution "Moscow Institute of Cancer Research named after P.A. Hertsen" Ministry of Health of Russian Federation

Moscow, 194044, Russia

Location

State Health Institution of Moscow "Moscow City Oncology Hospital #62 of Moscow Board of Health"

Moscow Region, 143423, Russia

Location

Murmansk Regional Oncology Dispensary

Murmansk, 183047, Russia

Location

Nizhny Novgorod Region State Budgetary Healthcare Facility "Clinical Diagnostics Center"

Nizhny Novgorod, 603006, Russia

Location

State Healthcare Facility "Nizhny Novgorod Regional Oncology Dispensary"

Nizhny Novgorod, Russia

Location

City Clinical Hospital №1

Novosibirsk, 630047, Russia

Location

Regional State Health Institution "Orlov Oncology Dispansary"

Oryol, 302020, Russia

Location

State Health Institution "Region Oncology Dispansary"

Penza, 440071, Russia

Location

Perm Region Oncology Dispensary

Perm, 614066, Russia

Location

Federal Government Budgetary Institution "Rostov Institute of Cancer Research" of Ministry of Health of Russian Federation

Rostov-on-Don, 314019, Russia

Location

Saint Petersburg City Clinical Oncology Center

Saint Petersburg, 197022, Russia

Location

St. Petersburg State Medical University n.a. I. P. Pavlov

Saint Petersburg, 197022, Russia

Location

N.N.Petrov Oncology Research Center

Saint Petersburg, 197758, Russia

Location

St. Petersburg Research and Practice Center for Secondary Care in Oncology

Saint Petersburg, 197758, Russia

Location

Military Medical Academy named after S.M. Kirov

Saint Petersburg, Russia

Location

Russian scientific center of radiology and surgery technologies

Saint Petersburg, Russia

Location

State-financed Health Institution "Samara Region Clinical Oncology Dispansary"

Samara, 443031, Russia

Location

Oncology Dispensary 2

Sochi, 354057, Russia

Location

State-financed Health Institution "Stavropol Region Clinical Oncology Dispansary"

Stavropol, 355047, Russia

Location

Volgograd District Oncology Dispensary №1

Volgograd, 400138, Russia

Location

Volgograd Regional Oncology Dispensary №3

Volgograd, 404130, Russia

Location

State Health Institution "Voronezh Region Clinical Oncology Dispansary"

Voronezh, 394000, Russia

Location

Donetsk City Oncology Dispensary

Donetsk, Ukraine

Location

Donetsk Regional Antitumor Center

Donetsk, Ukraine

Location

Kharkiv Regional Clinical Oncology Center

Kharkiv, Ukraine

Location

Kryvyi Rih Oncology Dispensary

Kryvyi Rih, Ukraine

Location

Lviv State Regional Cancer Diagnostic and Treatment Center

Lviv, Ukraine

Location

City Hospital № 2

Makiivka, Ukraine

Location

Poltava Regional Clinical Oncology Dispensary

Poltava, Ukraine

Location

Zakarpatskyi Clinical Oncology Dispensary

Uzhhorod, Ukraine

Location

Vinnytsia Regional Clinical Oncology Dispensary

Vinnytsia, Ukraine

Location

Zaporizhia Regional Clinical Oncology Dispensary

Zaporizhia, Ukraine

Location

Related Publications (1)

• Stroyakovskiy DL, Fadeeva NV, Matrosova MP, Shelepen KG, Adamchuk GA, Roy B, Nagarkar R, Kalloli M, Zhuravleva D, Voevodin GD, Shustova MS, Kryukov F. Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-021 with reference bevacizumab. BMC Cancer. 2022 Feb 1;22(1):129. doi: 10.1186/s12885-022-09243-7.

  PMID: 35105329 DERIVED

Related Links

• Stroyakovskiy, D.L., Fadeeva, N.V., Matrosova, M.P. et al. Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-021 with reference bevacizumab. BMC Cancer 22, 129 (2022). https://doi.org/10.1186/s12885-022-09243-7

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Bevacizumab; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Results Point of Contact

• Title: Feder Krykov
• Organization: BIOCAD

kryukov@biocad.ru

+7 (812) 380 4933

Study Officials

• Yulia Linkova, MD, PhD

  Director of Clinical Development Department, BIOCAD

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2012
• First Posted: January 9, 2013
• Study Start: October 1, 2012
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: January 11, 2024
• Results First Posted: October 24, 2016

Record last verified: 2023-04

Locations

IN (3); UA (10); BE (4); RU (27)