Study To Evaluate the Efficacy and Safety Of Bevacizumab, and Associated Biomarkers, In Combination With Paclitaxel Compared With Paclitaxel Plus Placebo as First-line Treatment Of Patients With Her2-Negative Metastatic Breast Cancer
- Conditions
- Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT01663727
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This is a Phase III, randomized, double-blind, placebo-controlled multicenter study to evaluate the efficacy and safety of bevacizumab administered in combination with paclitaxel in patients with previously untreated, locally recurrent, or metastatic HER2-negative breast cancer. Patients will be randomized to one of two treatment arms: bevacizumab or placebo. All patients will be given an intravenous (IV) infusion of of paclitaxel (90 mg/m2) for 3 weeks during each 28-day cycle. bevacizumab or placebo (10 mg/kg) will be administered by IV infusion on Days 1 and 15 of each 28-day cycle. Patients will be treated until disease progression, unacceptable toxicity or death from any cause occurs.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 481
- Histologically or cytologically confirmed, HER2-negative adenocarcinoma of the breast, with measurable or non-measurable locally recurrent or metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
- ECOG performance status of 0 or 1
- For women of childbearing potential, use of an acceptable and effective method of non-hormonal contraception
- For patients who have received recent radiotherapy, recovery prior to randomization from any significant acute toxicity, and radiation treatments have to be completed more than 3 weeks from randomization
Disease-Specific Exclusions:
- HER2-positive status
- Prior chemotherapy for locally recurrent or metastatic disease
- Prior hormonal therapy < 2 weeks prior to randomization
- Prior adjuvant or neo-adjuvant chemotherapy is allowed, provided its conclusion has been for at least 12 months prior to randomization
- Investigational therapy within 28 days of randomization
General Medical Exclusions:
- Life expectancy of < 12 weeks
- Inadequate organ function
- Uncontrolled serious medical or psychiatric illness
- Active infection requiring intravenous (IV) antibiotics at screening
- Pregnancy or lactation
- History of other malignancies within 5 years prior to screening, except for tumors with a negligible risk for metastasis or death
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A Bevacizumab [Avastin] Paclitaxel + Bevacizumab \[Avastin\] B Paclitaxel Paclitaxel + Placebo B Placebo Paclitaxel + Placebo A Paclitaxel Paclitaxel + Bevacizumab \[Avastin\]
- Primary Outcome Measures
Name Time Method Percentage of Participants With Progression or Death in Intent-to-Treat (ITT) Population Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 117.7 weeks) Tumor assessment was performed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by investigator. Disease progression was defined as at least 20 percent (%) increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 millimeter (mm), unequivocal progression of existing non-target lesions, or presence of new lesions.
Progression Free Survival (PFS) in ITT Population Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 117.7 weeks) PFS was defined as the interval between the date of randomization and the first documentation of progressive disease or death from any cause. Tumor assessment was performed as per RECIST v1.1 by investigator. Disease progression was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or presence of new lesions. PFS was estimated using Kaplan Meier method.
PFS in High Baseline Plasma VEGF-A ITT Population Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 111.3 weeks) PFS was defined as the interval between the date of randomization and the first documentation of progressive disease or death from any cause. Tumor assessment was performed as per RECIST v1.1 by investigator. Disease progression was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or presence of new lesions. PFS was estimated using Kaplan Meier method.
Percentage of Participants With Progression or Death in High Baseline Plasma Vascular Endothelial Growth Factor-A (VEGF-A) ITT Population Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 111.3 weeks) Tumor assessment was performed as per RECIST v1.1 by investigator. Disease progression was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or presence of new lesions.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Who Died - ITT Population From randomization till death or clinical cut-off (up to 244 weeks) Percentage of Participants With an Objective Response - ITT Population Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 117.7 weeks) Objective response was defined as having a Complete Response (CR) or Partial Response (PR) according to a RECIST criteria v 1.1. CR was defined as disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to \<10 mm in short axis and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. Measurable disease was defined by the presence of at least one measurable lesion by clinical measurement, chest x-ray, computed tomography (CT), or magnetic resonance imaging (MRI).
Percentage of Participants With an Objective Response - High Baseline Plasma VEGF-A ITT Population Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 111.3 weeks) Objective response was defined as having a CR or PR according to a RECIST criteria v 1.1. CR was defined as disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to \<10 mm in short axis and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. Measurable disease was defined by the presence of at least one measurable lesion by clinical measurement, chest x-ray, CT, or MRI.
Overall Survival (OS) - ITT Population From randomization till death or clinical cut-off (up to 244 weeks) OS was defined as the interval between the date of randomization and death from any cause. OS was estimated using Kaplan Meier method.
Secondary: Percentage of Participants Who Were Alive at 1 Year - High Baseline Plasma VEGF-A ITT Population 1 year Percentage of Participants Who Died - High Baseline Plasma VEGF-A ITT Population From randomization till death or clinical cut-off (up to 244 weeks) OS - High Baseline Plasma VEGF-A ITT Population From randomization till death or clinical cut-off (up to 244 weeks) OS was defined as the interval between the date of randomization and death from any cause. OS was estimated using Kaplan Meier method.
Duration of Response - ITT Population Baseline, every 8 weeks until documented disease progression or clinical cut-off (up to 117.7 weeks) Duration of response was defined as the time from the initial date of the objective response to documented disease progression or death (whichever occurred first). Objective response was defined as having a CR or PR according to a RECIST criteria v 1.1. CR was defined as disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to \<10 mm in short axis and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. Disease progression was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or presence of new lesions. Analysis was performed using Kaplan Meier method.
Percentage of Participants Who Were Alive at 1 Year - ITT Population 1 year Duration of Response - High Baseline Plasma VEGF-A ITT Population Baseline, every 8 weeks until documented disease progression or clinical cut-off (up to 111.3 weeks) Duration of response was defined as the time from the initial date of the objective response to documented disease progression or death (whichever occurred first). Objective response was defined as having a CR or PR according to a RECIST criteria v 1.1. CR was defined as disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to \<10 mm in short axis and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. Disease progression was defined at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or presence of new lesions. Analysis was performed using Kaplan Meier method.
Trial Locations
- Locations (173)
Univ of Texas Medical Branch
🇺🇸Galveston, Texas, United States
Texas Oncology, P.A.
🇺🇸The Woodlands, Texas, United States
Wellmonth Physician Services
🇺🇸Bristol, Virginia, United States
West Virginia University; Endocrinology
🇺🇸Morgantown, West Virginia, United States
Kumamoto City Hospital
🇯🇵Kumamoto, Japan
Iwate Medical University Hospital
🇯🇵Iwate, Japan
Fondazione Salvatore Maugeri IRCCS
🇮🇹Pavia, Lombardia, Italy
Gifu University Hospital
🇯🇵Gifu, Japan
NHO Kyushu Cancer Center
🇯🇵Fukuoka, Japan
Lviv State Oncological Regional Treatment and Diagnostic Center
🇺🇦Lviv, Ukraine
CCCH City Oncological Center SHEI Uzhgorod NU
🇺🇦Uzhgorod, Ukraine
Velindre Cancer Centre
🇬🇧Cardiff, United Kingdom
Peterborough City Hospital
🇬🇧Peterborough, United Kingdom
Hopelands Cancer Centre Durban
🇿🇦Durban, South Africa
Medical Research Centre
🇵🇦Panama, Panama
SHI Republican Clinical Oncological Dispensary of HM RT
🇷🇺Kazan, Russian Federation
NHO Osaka National Hospital
🇯🇵Osaka, Japan
NHO Shikoku Cancer Center; Dept of Respiratory Medicine
🇯🇵Ehime, Japan
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hyogo College of Medicine Hospital
🇯🇵Hyogo, Japan
Kindai University Hospital
🇯🇵Osaka, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
University of Pretoria; Department of Medical Oncology
🇿🇦Pretoria, South Africa
Kyiv Сity Clinical Oncological Center
🇺🇦Kyiv, Ukraine
RCI Sumy Regional Clinical Oncological Dispensary
🇺🇦Sumy, Ukraine
Medical and Prophylactic Institution Volyn Regional Oncological Dispensary
🇺🇦Lutsk, Ukraine
Western General Hospital
🇬🇧Edinburgh, United Kingdom
Mary Potter Oncology Centre
🇿🇦Groenkloof, South Africa
Mount Vernon Hospital
🇬🇧Middlesex, United Kingdom
CI Dnipropetrovsk CMCH 4 of Dnipropetrovsk RC Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU
🇺🇦Dnipropetrovsk, Ukraine
Royal Devon and Exeter Hospital (Wonford)
🇬🇧Exeter, United Kingdom
Hiroshima University Hospital
🇯🇵Hiroshima, Japan
Asan Medical Center.
🇰🇷Seoul, Korea, Republic of
City Clinical Oncology Dispensary
🇷🇺Saint-Petersburg, Russian Federation
Cape Town Oncology Trials
🇿🇦Cape Town, South Africa
Non-state Healthcare Institution "Road Clinical Hospital of JSC Russian Railways"
🇷🇺St. Petersburg, Russian Federation
Seoul National University Bundang Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Severance Hospital, Yonsei University Health System; Pharmacy
🇰🇷Seoul, Korea, Republic of
NHO Hokkaido Cancer Center
🇯🇵Sapporo-shi, Japan
Peachtree Hematology & Oncology Consultants, Pc
🇺🇸Atlanta, Georgia, United States
Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
Northeast Georgia Cancer Care LLC
🇺🇸Athens, Georgia, United States
Washington University; Center for Adv Medicine
🇺🇸Saint Louis, Missouri, United States
Long Beach Memorial Medical Center; Oncology
🇺🇸Long Beach, California, United States
CTPI Chernihiv Regional Oncological Dispensary
🇷🇺Chernihiv, Russian Federation
Ospedale Mater Salutis
🇮🇹Legnago (VR), Lombardia, Italy
Missouri Cancer Associates
🇺🇸Columbia, Missouri, United States
Pennsylvania Oncology Hematology Associates, Inc.; PA Oncology & Hematology
🇺🇸Philadelphia, Pennsylvania, United States
Hospital Provincial del Centenario
🇦🇷Rosario, Argentina
Texas Oncology, P.A. - Fort Worth
🇺🇸Fort Worth, Texas, United States
Virginia Oncology Associates - Hampton
🇺🇸Hampton, Virginia, United States
Texas Oncology, P.A. - Dallas Presbyterian
🇺🇸Dallas, Texas, United States
Centro Oncologico Riojano Integral (CORI)
🇦🇷La Rioja, Argentina
CHU Ambroise Paré; Hematology and Oncology Department
🇧🇪Mons, Belgium
Northwest Medical Specialties, PLLC; Research Department
🇺🇸Tacoma, Washington, United States
Washington Hospital
🇺🇸Washington, District of Columbia, United States
The Jones Clinic, PC
🇺🇸New Albany, Mississippi, United States
Hematology Oncology Associates of the Treasure Coast
🇺🇸Port Saint Lucie, Florida, United States
Texas Oncology-Medical City Dallas
🇺🇸Dallas, Texas, United States
Oncology and Hematology Assoc. of SW VA, Inc. - Low Moor
🇺🇸Low Moor, Virginia, United States
UZ Brussel
🇧🇪Brussel, Belgium
UZ Antwerpen
🇧🇪Edegem, Belgium
Lahey Clinic Inc. - PARENT ACCOUNT
🇺🇸Burlington, Massachusetts, United States
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Virginia Oncology Associates - Virginia Beach
🇺🇸Virginia Beach, Virginia, United States
Centro de Investigacion Pergamino SA
🇦🇷Pergamino, Argentina
Texas Oncology- Southwest Fort Worth
🇺🇸Fort Worth, Texas, United States
Instituto de OncologÃa de Rosario
🇦🇷Rosario, Argentina
ISIS Clinica Especializada
🇦🇷Santa Fe, Argentina
FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"
🇷🇺Saint-Petersburg, Russian Federation
Universitaetsklinikum Ulm
🇩🇪Ulm, Germany
Hospital das Clinicas - FMUSP Ribeirao Preto
🇧🇷Ribeirao Preto, SP, Brazil
Texas Oncology, P.A. - Garland
🇺🇸Garland, Texas, United States
Sanatorio Parque S.A.
🇦🇷Rosario, Santa FE, Argentina
Texas Oncology Plano West
🇺🇸Plano, Texas, United States
Azienda Ospedaliera A. Cardarelli
🇮🇹Napoli, Campania, Italy
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
GHdC Site Saint-Joseph
🇧🇪Gilly (Charleroi), Belgium
Oncology and Hematology Assoc. of SW VA, Inc.
🇺🇸Salem, Virginia, United States
Oncology and Hematology Assoc. of SW VA, Inc. - Wytheville
🇺🇸Wytheville, Virginia, United States
Hospital Britanico de Buenos Aires
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Instituto CAICI
🇦🇷Rosario, Argentina
Instituto de Investigaciones ClÃnicas Quilmes
🇦🇷Quilmes, Argentina
Hospital da Cidade de Passo Fundo; Centro de Pesquisa em Oncologia
🇧🇷Passo Fundo, RS, Brazil
National Hospital; Oncotherapy Dept
🇿🇦Bloemfontein, South Africa
UMHAT Tsaritsa Yoanna - ISUL, EAD
🇧🇬Sofia, Bulgaria
St. Johannes Hospital; Klinik fuer innere Medizin II, Onkologie, Haematologie
🇩🇪Dortmund, Germany
Universidade Federal de Sao Paulo - UNIFESP
🇧🇷Sao Paulo, SP, Brazil
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany
St. Elisabeth-Krankenhaus
🇩🇪Köln, Germany
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
IU Cancer Pavilion
🇺🇸Indianapolis, Indiana, United States
CancerCare Centers of South Texas
🇺🇸San Antonio, Texas, United States
SCRI-Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Cancer Care Centers of South Texas
🇺🇸San Antonio, Texas, United States
Oncology & Hematology Associates of SW Va Inc. - Market Street
🇺🇸Christiansburg, Virginia, United States
SHATOD - Sofia City, EOOD
🇧🇬Sofia, Bulgaria
Complex Oncological Center - Plovdiv, EOOD
🇧🇬Plovdiv, Bulgaria
SHATOD - Sofia District, EOOD
🇧🇬Sofia, Bulgaria
COC - Veliko Tarnovo
🇧🇬Veliko Tarnovo, Bulgaria
Fundacion Arturo Lopez Perez
🇨🇱Santiago, Chile
MHAT Dr. Tota Venkova AD
🇧🇬Gabrovo, Bulgaria
SHATOD Haskovo EOOD
🇧🇬Haskovo, Bulgaria
MHAT Serdika, EOOD
🇧🇬Sofia, Bulgaria
Instituto Nacional del Cancer
🇨🇱Santiago, Chile
Complex Oncological Center - Shumen, EOOD; Department of Chemotherapy
🇧🇬Shumen, Bulgaria
Instituto Oncologico Ltda.
🇨🇱Viña del Mar, Chile
Institutul Oncologic Prof. Dr. Ion Chiricuta Cluj-Napoca; Radioterapie I - Oncologie
🇷🇴Cluj-Napoca, Romania
SHATOD Dr. Marko Antonov Markov-Varna, EOOD
🇧🇬Varna, Bulgaria
Centro de Estudios Oncologicos de Santiago (CEOS) Oncologia
🇨🇱Santiago, Chile
Institutul Oncologic "Prof. Dr. Al. Trestioreanu"
🇷🇴Bucuresti, Romania
Centro Hemato Oncologico Panama
🇵🇦Panama, Panama
Centro de Pesquisas Oncologicas - CEPON
🇧🇷Florianopolis, SC, Brazil
Tokai University Hospital
🇯🇵Kanagawa, Japan
Tohoku University Hospital
🇯🇵Miyagi, Japan
Toranomon Hospital
🇯🇵Tokyo, Japan
Osaka International Cancer Institute
🇯🇵Osaka, Japan
Shizuoka General Hospital
🇯🇵Shizuoka-shi, Japan
Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
🇯🇵Tokyo, Japan
Cancer Care Centers of S Texas
🇺🇸Kerrville, Texas, United States
Texas Oncology- Longview Cancer Center
🇺🇸Longview, Texas, United States
Wilshire Oncology Medical Group
🇺🇸West Covina, California, United States
Sylvester Comprehensive Cancer Center - Deerfield Beach; Sylvester Cancer Center
🇺🇸Deerfield Beach, Florida, United States
Tenet Health System Desert Inc
🇺🇸Palm Springs, California, United States
Wilshire Oncology Medical Group; Oncology
🇺🇸Pomona, California, United States
Florida Cancer Specialists - Broadway
🇺🇸Fort Myers, Florida, United States
Maryland Oncology Hematology, P.A.
🇺🇸Columbia, Maryland, United States
BRCR Medical Center, Inc.
🇺🇸Plantation, Florida, United States
Greater Baltimore Medical Center
🇺🇸Baltimore, Maryland, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
ProMedica Hickman Cancer Center at Flower Hospital; Hickman Cancer Center
🇺🇸Sylvania, Ohio, United States
Virginia Cancer Specialists - Leesburg
🇺🇸Leesburg, Pennsylvania, United States
Signal Point Clinical; Research Center, LLC
🇺🇸Middletown, Ohio, United States
Texas Oncology, P.A. - Tyler
🇺🇸The Woodlands, Texas, United States
Virginia Cancer Specialists - Alexandria
🇺🇸Alexandria, Virginia, United States
Virginia Oncology Associates - Chesapeake
🇺🇸Chesapeake, Virginia, United States
Fairfax Northern Virginia Hematology-Oncology PC
🇺🇸Arlington, Virginia, United States
Virginia Oncology Associates - New Port News
🇺🇸Newport News, Virginia, United States
Oncology & Hematolgy Associates of SW Va Inc. - Roanoke
🇺🇸Roanoke, Virginia, United States
Virginia Cancer Specialists - Gainsville
🇺🇸Gainesville, Virginia, United States
AZ KLINA
🇧🇪Brasschaat, Belgium
Clinica de Tratamento e Pesquisa Oncologica - Oncotek
🇧🇷Brasilia, DF, Brazil
Hospital Sao Lucas - PUCRS; Pesquisa Clinica
🇧🇷Porto Alegre, RS, Brazil
Clinica de Oncologia de Porto Alegre - CliniOnco
🇧🇷Porto Alegre, RS, Brazil
Clinica de Neoplasias Litoral
🇧🇷Itajai, SC, Brazil
Hakuaikai Sagara Hospital
🇯🇵Kagoshima, Japan
Studienzentrum Aschaffenburg
🇩🇪Aschaffenburg, Germany
Wilhelm-Anton-Hospital gGmbH
🇩🇪Goch, Germany
Ospedale degli Infermi
🇮🇹Rimini, Emilia-Romagna, Italy
Ospedale San Raffaele
🇮🇹Milano, Lombardia, Italy
Ospedale Casa Sollievo Della Sofferenza IRCCS
🇮🇹San Giovanni Rotondo, Puglia, Italy
Ospedale Versilia
🇮🇹Lido Di Camaiore, Toscana, Italy
Niigata Cancer Center Hospital
🇯🇵Niigata, Japan
Kumamoto University Hospital
🇯🇵Kumamoto, Japan
Juntendo University Hospital
🇯🇵Tokyo, Japan
National Cancer Centre
🇰🇷Gyeonggi-do, Korea, Republic of
Oncomed SRL
🇷🇴Timisoara, Romania
Medisprof SRL
🇷🇴Cluj-Napoca, Romania
Regional Clinical Oncology Dispensary
🇷🇺Krasnodar, Russian Federation
SBEIHPE SSMU n.a. I.P.Pavlov of MOH and SD of RF
🇷🇺Saint-Petersburg, Russian Federation
Samara Regional Oncology Dispensary
🇷🇺Samara, Russian Federation
CCTPI Donetsk Regional Antitumor Center
🇺🇦Donetsk, Ukraine
Hopelands Cancer Centre
🇿🇦Hilton, South Africa
Cancercare
🇿🇦Port Elizabeth, South Africa
Derriford Hospital; Clinical Neurology Research Group
🇬🇧Plymouth, United Kingdom
Texas Oncology, P.A. - McAllen; South Texas Cancer Center-McAllen
🇺🇸McAllen, Texas, United States
University of Toledo; Dept. of Medicine
🇺🇸Toledo, Ohio, United States
Hematology Oncology Associates of Fredericksburg, Inc.
🇺🇸Fredericksburg, Virginia, United States
Hospital Nossa Senhora da Conceicao
🇧🇷Porto Alegre, RS, Brazil
CI Cherkasy Regional Oncological Dispensary of Cherkasy RC RC of Clinical Oncology
🇺🇦Cherkassy, Ukraine
Medical University of South Carolina; Division of Hematology-Oncology
🇺🇸Charleston, South Carolina, United States
Kaiser Foundation Hospital; Dr. Eron's Office
🇺🇸Honolulu, Hawaii, United States
FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
🇷🇺Moscow, Russian Federation