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

NCT ID: NCT01763645

Last Updated: 2024-01-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 353 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2014-11-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: 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).

Paclitaxel

Intervention Type: 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)

Carboplatin

Intervention Type: 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)

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.

Group Type: ACTIVE_COMPARATOR

Bevacizumab

Intervention Type: 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).

Paclitaxel

Intervention Type: 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)

Carboplatin

Intervention Type: 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).

Interventions

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).

Intervention Type: 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)

Intervention Type: 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).

Intervention Type: DRUG

Other Intervention Names

Avastin; BCD-021; Taxacad

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biocad

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yulia Linkova, MD, PhD

Role: STUDY_DIRECTOR

Director of Clinical Development Department, BIOCAD

Locations

Brest Regional Clinical Dispensary

Brest, , Belarus

Grodno Regional Clinical Hospital

Grodno, , Belarus

Gomel Regional Clinical Oncology Dispensary

Homyel, , Belarus

Vitebsk Regional Clinical Oncology Dispensary

Vitebsk, , Belarus

HCG Bangalore Institute of Oncology

Bangalore, , India

M.S.Ramaiah Memorial Hospital

Bangalore, , India

Narayana Hrudayalaya Hospitals

Bangalore, , India

Arkhangelsk District Clinical Oncology Dispensary

Arkhangelsk, , Russia

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

Chelyabinsk, , Russia

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

Chelyabinsk, , Russia

State Healthcare Facility "Kursk Regional Oncology Dispensary"

Kursk, , Russia

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

Moscow, , Russia

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

Moscow, , Russia

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

Moscow Region, , Russia

Murmansk Regional Oncology Dispensary

Murmansk, , Russia

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

Nizhny Novgorod, , Russia

State Healthcare Facility "Nizhny Novgorod Regional Oncology Dispensary"

Nizhny Novgorod, , Russia

City Clinical Hospital №1

Novosibirsk, , Russia

Regional State Health Institution "Orlov Oncology Dispansary"

Oryol, , Russia

State Health Institution "Region Oncology Dispansary"

Penza, , Russia

Perm Region Oncology Dispensary

Perm, , Russia

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

Rostov-on-Don, , Russia

Saint Petersburg City Clinical Oncology Center

Saint Petersburg, , Russia

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

Saint Petersburg, , Russia

N.N.Petrov Oncology Research Center

Saint Petersburg, , Russia

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

Saint Petersburg, , Russia

Military Medical Academy named after S.M. Kirov

Saint Petersburg, , Russia

Russian scientific center of radiology and surgery technologies

Saint Petersburg, , Russia

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

Samara, , Russia

Oncology Dispensary 2

Sochi, , Russia

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

Stavropol, , Russia

Volgograd District Oncology Dispensary №1

Volgograd, , Russia

Volgograd Regional Oncology Dispensary №3

Volgograd, , Russia

State Health Institution "Voronezh Region Clinical Oncology Dispansary"

Voronezh, , Russia

Donetsk City Oncology Dispensary

Donetsk, , Ukraine

Donetsk Regional Antitumor Center

Donetsk, , Ukraine

Kharkiv Regional Clinical Oncology Center

Kharkiv, , Ukraine

Kryvyi Rih Oncology Dispensary

Kryvyi Rih, , Ukraine

Lviv State Regional Cancer Diagnostic and Treatment Center

Lviv, , Ukraine

City Hospital № 2

Makiivka, , Ukraine

Poltava Regional Clinical Oncology Dispensary

Poltava, , Ukraine

Zakarpatskyi Clinical Oncology Dispensary

Uzhhorod, , Ukraine

Vinnytsia Regional Clinical Oncology Dispensary

Vinnytsia, , Ukraine

Zaporizhia Regional Clinical Oncology Dispensary

Zaporizhia, , Ukraine

Countries

Belarus; India; Russia; Ukraine

References

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.

Reference Type: DERIVED

PMID: 35105329 (View on PubMed)

Related Links

https://doi.org/10.1186/s12885-022-09243-7

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

Other Identifiers

BCD-021-02

Identifier Type: -

Identifier Source: org_study_id