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
A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter 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
2 other identifiers
interventional
481
16 countries
178
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Aug 2012
Longer than P75 for phase_3
178 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 9, 2012
CompletedFirst Posted
Study publicly available on registry
August 13, 2012
CompletedStudy Start
First participant enrolled
August 27, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 30, 2014
CompletedResults Posted
Study results publicly available
February 10, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
November 21, 2017
CompletedJanuary 22, 2019
January 1, 2019
2.3 years
August 9, 2012
January 12, 2016
January 7, 2019
Conditions
Outcome Measures
Primary Outcomes (4)
Percentage of Participants With Progression or Death in Intent-to-Treat (ITT) Population
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.
Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 117.7 weeks)
Progression Free Survival (PFS) in ITT Population
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.
Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 117.7 weeks)
Percentage of Participants With Progression or Death in High Baseline Plasma Vascular Endothelial Growth Factor-A (VEGF-A) ITT Population
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.
Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 111.3 weeks)
PFS in High Baseline Plasma VEGF-A ITT Population
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.
Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 111.3 weeks)
Secondary Outcomes (10)
Percentage of Participants Who Died - ITT Population
From randomization till death or clinical cut-off (up to 244 weeks)
Overall Survival (OS) - ITT Population
From randomization till death or clinical cut-off (up to 244 weeks)
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)
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)
- +5 more secondary outcomes
Study Arms (2)
A
EXPERIMENTALPaclitaxel + Bevacizumab \[Avastin\]
B
EXPERIMENTALPaclitaxel + Placebo
Interventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (178)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
Arizona Cancer Center
Tucson, Arizona, 85724, United States
Wilshire Oncology Medical Group
Corona, California, 92879, United States
Wilshire Oncology Medical Group
Glendora, California, 91741, United States
Wilshire Oncology Medical Group
La Verne, California, 91750, United States
Long Beach Memorial Medical Center; Oncology
Long Beach, California, 90806, United States
Tenet Health System Desert Inc
Palm Springs, California, 92262, United States
Wilshire Oncology Medical Group; Oncology
Pomona, California, 91767, United States
Wilshire Oncology Medical Group
Rancho Cucamonga, California, 91730, United States
Wilshire Oncology Medical Group
West Covina, California, 91790, United States
Washington Hospital
Washington D.C., District of Columbia, 20010, United States
Sylvester Comprehensive Cancer Center - Deerfield Beach; Sylvester Cancer Center
Deerfield Beach, Florida, 33442, United States
Florida Cancer Specialists - Broadway
Fort Myers, Florida, 33901, United States
BRCR Medical Center, Inc.
Plantation, Florida, 33322, United States
Hematology Oncology Associates of the Treasure Coast
Port Saint Lucie, Florida, 34952, United States
Northeast Georgia Cancer Care LLC
Athens, Georgia, 30607, United States
Peachtree Hematology & Oncology Consultants, Pc
Atlanta, Georgia, 30318, United States
Kaiser Foundation Hospital; Dr. Eron's Office
Honolulu, Hawaii, 96819, United States
IU Cancer Pavilion
Indianapolis, Indiana, 46202, United States
Greater Baltimore Medical Center
Baltimore, Maryland, 21204, United States
Maryland Oncology Hematology, P.A.
Columbia, Maryland, 21044, United States
Lahey Clinic Inc. - PARENT ACCOUNT
Burlington, Massachusetts, 01805, United States
The Jones Clinic, PC
New Albany, Mississippi, 38652, United States
Missouri Cancer Associates
Columbia, Missouri, 65201, United States
Washington University; Center for Adv Medicine
St Louis, Missouri, 63110, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Signal Point Clinical; Research Center, LLC
Middletown, Ohio, 45042, United States
ProMedica Hickman Cancer Center at Flower Hospital; Hickman Cancer Center
Sylvania, Ohio, 43560, United States
University of Toledo; Dept. of Medicine
Toledo, Ohio, 43614, United States
Virginia Cancer Specialists - Leesburg
Leesburg, Pennsylvania, 20176, United States
Pennsylvania Oncology Hematology Associates, Inc.; PA Oncology & Hematology
Philadelphia, Pennsylvania, 19106, United States
Medical University of South Carolina; Division of Hematology-Oncology
Charleston, South Carolina, 29425, United States
SCRI-Tennessee Oncology
Nashville, Tennessee, 37203, United States
Texas Oncology-Medical City Dallas
Dallas, Texas, 75230, United States
Texas Oncology, P.A. - Dallas Presbyterian
Dallas, Texas, 75231, United States
Texas Oncology, P.A. - Fort Worth
Fort Worth, Texas, 76104, United States
Texas Oncology- Southwest Fort Worth
Fort Worth, Texas, 76132, United States
Univ of Texas Medical Branch
Galveston, Texas, 77555, United States
Texas Oncology, P.A. - Garland
Garland, Texas, 77060, United States
Cancer Care Centers of S Texas
Kerrville, Texas, 78028, United States
Texas Oncology- Longview Cancer Center
Longview, Texas, 75601, United States
Texas Oncology, P.A. - McAllen; South Texas Cancer Center-McAllen
McAllen, Texas, 78503, United States
Texas Oncology Plano West
Plano, Texas, 75093, United States
Cancer Care Centers of South Texas
San Antonio, Texas, 78212, United States
Cancer Care Centers of South Texas
San Antonio, Texas, 78217, United States
CancerCare Centers of South Texas
San Antonio, Texas, 78258, United States
Texas Oncology, P.A. - Tyler
The Woodlands, Texas, 77060, United States
Texas Oncology, P.A.
The Woodlands, Texas, 77060, United States
Virginia Cancer Specialists - Alexandria
Alexandria, Virginia, 22304, United States
Fairfax Northern Virginia Hematology-Oncology PC
Arlington, Virginia, 22205, United States
Wellmonth Physician Services
Bristol, Virginia, 24201, United States
Virginia Oncology Associates - Chesapeake
Chesapeake, Virginia, 23320, United States
Oncology & Hematology Associates of SW Va Inc. - Market Street
Christiansburg, Virginia, 24073, United States
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031, United States
Hematology Oncology Associates of Fredericksburg, Inc.
Fredericksburg, Virginia, 22408, United States
Virginia Cancer Specialists - Gainsville
Gainesville, Virginia, 20155, United States
Virginia Oncology Associates - Hampton
Hampton, Virginia, 23666, United States
Oncology and Hematology Assoc. of SW VA, Inc. - Low Moor
Low Moor, Virginia, 24457, United States
Virginia Oncology Associates - New Port News
Newport News, Virginia, 23606, United States
Virginia Oncology Associates
Norfolk, Virginia, 23502, United States
Oncology & Hematolgy Associates of SW Va Inc. - Roanoke
Roanoke, Virginia, 24014, United States
Oncology and Hematology Assoc. of SW VA, Inc.
Salem, Virginia, 77060, United States
Virginia Oncology Associates - Virginia Beach
Virginia Beach, Virginia, 23456, United States
Oncology and Hematology Assoc. of SW VA, Inc. - Wytheville
Wytheville, Virginia, 24382, United States
Northwest Medical Specialties, PLLC; Research Department
Tacoma, Washington, 98405, United States
West Virginia University; Endocrinology
Morgantown, West Virginia, 26506, United States
Hospital Britanico de Buenos Aires
Ciudad Autonoma Buenos Aires, C1284AEB, Argentina
Centro Oncologico Riojano Integral (CORI)
La Rioja, F5300COE, Argentina
Centro de Investigacion Pergamino SA
Pergamino, B2700CPM, Argentina
Instituto de Investigaciones Clínicas Quilmes
Quilmes, 1878, Argentina
Hospital Provincial del Centenario
Rosario, 2000, Argentina
Instituto CAICI
Rosario, S2000CVB, Argentina
Instituto de Oncología de Rosario
Rosario, S2000KZE, Argentina
Sanatorio Parque S.A.
Rosario, Santa FE, S2000DSV, Argentina
ISIS Clinica Especializada
Santa Fe, 03000, Argentina
AZ KLINA
Brasschaat, 2930, Belgium
UZ Brussel
Brussels, 1090, Belgium
UZ Antwerpen
Edegem, 2650, Belgium
GHdC Site Saint-Joseph
Gilly (Charleroi), 6000, Belgium
CHU Ambroise Paré; Hematology and Oncology Department
Mons, 7000, Belgium
Clinica de Tratamento e Pesquisa Oncologica - Oncotek
Brasília, Federal District, 70390-055, Brazil
Hospital da Cidade de Passo Fundo; Centro de Pesquisa em Oncologia
Passo Fundo, Rio Grande do Sul, 99010-260, Brazil
Hospital Sao Lucas - PUCRS; Pesquisa Clinica
Porto Alegre, Rio Grande do Sul, 90110-270, Brazil
Clinica de Oncologia de Porto Alegre - CliniOnco
Porto Alegre, Rio Grande do Sul, 90430-090, Brazil
Hospital Nossa Senhora da Conceicao
Porto Alegre, Rio Grande do Sul, 91350-200, Brazil
Centro de Pesquisas Oncologicas - CEPON
Florianópolis, Santa Catarina, 88034-000, Brazil
Clinica de Neoplasias Litoral
Itajaí, Santa Catarina, 88301-220, Brazil
Hospital das Clinicas - FMUSP Ribeirao Preto
Ribeirão Preto, São Paulo, 14048-900, Brazil
Universidade Federal de Sao Paulo - UNIFESP
São Paulo, São Paulo, 22793-080, Brazil
MHAT Dr. Tota Venkova AD
Gabrovo, 5300, Bulgaria
SHATOD Haskovo EOOD
Haskovo, 6300, Bulgaria
Complex Oncological Center - Plovdiv, EOOD
Plovdiv, 4004, Bulgaria
Complex Oncological Center - Shumen, EOOD; Department of Chemotherapy
Shumen, 9700, Bulgaria
SHATOD - Sofia District, EOOD
Sofia, 1233, Bulgaria
MHAT Serdika, EOOD
Sofia, 1303, Bulgaria
UMHAT Tsaritsa Yoanna - ISUL, EAD
Sofia, 1527, Bulgaria
SHATOD - Sofia City, EOOD
Sofia, 1784, Bulgaria
SHATOD Dr. Marko Antonov Markov-Varna, EOOD
Varna, 9010, Bulgaria
COC - Veliko Tarnovo
Veliko Tarnovo, 5000, Bulgaria
Centro de Estudios Oncologicos de Santiago (CEOS) Oncologia
Santiago, 7500921, Chile
Fundacion Arturo Lopez Perez
Santiago, 7500921, Chile
Instituto Nacional del Cancer
Santiago, 8380000, Chile
Instituto Oncologico Ltda.
Viña del Mar, Chile
Studienzentrum Aschaffenburg
Aschaffenburg, 63739, Germany
St. Elisabeth-Krankenhaus
Cologne, 50935, Germany
St. Johannes Hospital; Klinik fuer innere Medizin II, Onkologie, Haematologie
Dortmund, 44137, Germany
Wilhelm-Anton-Hospital gGmbH
Goch, 47574, Germany
Universitätsklinikum Heidelberg
Heidelberg, 69120, Germany
Universitaetsklinikum Ulm
Ulm, 89081, Germany
Ospedale Casa Sollievo Della Sofferenza IRCCS
San Giovanni Rotondo, Apulia, 71013, Italy
Azienda Ospedaliera A. Cardarelli
Napoli, Campania, 80131, Italy
Ospedale degli Infermi
Rimini, Emilia-Romagna, 47923, Italy
Ospedale Mater Salutis
Legnago (VR), Lombardy, 37045, Italy
Ospedale San Raffaele
Milan, Lombardy, 20132, Italy
Fondazione Salvatore Maugeri IRCCS
Pavia, Lombardy, 27100, Italy
Ospedale Versilia
Lido di Camaiore, Tuscany, 55043, Italy
NHO Shikoku Cancer Center; Dept of Respiratory Medicine
Ehime, 791-0280, Japan
NHO Kyushu Cancer Center
Fukuoka, 811-1395, Japan
Gifu University Hospital
Gifu, 501-1194, Japan
Hiroshima University Hospital
Hiroshima, 734-8551, Japan
Hyogo College of Medicine Hospital
Hyōgo, 663-8501, Japan
Hakuaikai Sagara Hospital
Kagoshima, 892-0833, Japan
Tokai University Hospital
Kanagawa, 259-1193, Japan
Kumamoto University Hospital
Kumamoto, 860-8556, Japan
Kumamoto City Hospital
Kumamoto, 862-8505, Japan
Tohoku University Hospital
Miyagi, 980-8574, Japan
Niigata Cancer Center Hospital
Niigata, 951-8566, Japan
Iwate Medical University Hospital
Numakunai, 020-8505, Japan
NHO Osaka National Hospital
Osaka, 540-0006, Japan
Osaka International Cancer Institute
Osaka, 541-8567, Japan
Kindai University Hospital
Osaka, 589-8511, Japan
NHO Hokkaido Cancer Center
Sapporo, 003-0804, Japan
Shizuoka General Hospital
Shizuoka, 420-8527, Japan
Toranomon Hospital
Tokyo, 105-8470, Japan
Juntendo University Hospital
Tokyo, 113-8431, Japan
Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
Tokyo, 113-8677, Japan
Centro Hemato Oncologico Panama
Panama City, 0832, Panama
Medical Research Centre
Panama City, Panama
Institutul Oncologic "Prof. Dr. Al. Trestioreanu"
Bucharest, 022328, Romania
Institutul Oncologic Prof. Dr. Ion Chiricuta Cluj-Napoca; Radioterapie I - Oncologie
Cluj-Napoca, 400015, Romania
Medisprof SRL
Cluj-Napoca, 400058, Romania
Oncomed SRL
Timișoara, 300239, Romania
CTPI Chernihiv Regional Oncological Dispensary
Chernihiv, 14029, Russia
SHI Republican Clinical Oncological Dispensary of HM RT
Kazan', 420029, Russia
Regional Clinical Oncology Dispensary
Krasnodar, 350040, Russia
FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
Moscow, 115478, Russia
Non-state Healthcare Institution "Road Clinical Hospital of JSC Russian Railways"
Saint Petersburg, 195271, Russia
City Clinical Oncology Dispensary
Saint Petersburg, 197022, Russia
SBEIHPE SSMU n.a. I.P.Pavlov of MOH and SD of RF
Saint Petersburg, 197101, Russia
FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"
Saint Petersburg, Russia
Samara Regional Oncology Dispensary
Samara, 443031, Russia
National Hospital; Oncotherapy Dept
Bloemfontein, 9301, South Africa
Cape Town Oncology Trials
Cape Town, 7570, South Africa
Hopelands Cancer Centre Durban
Durban, 4091, South Africa
Mary Potter Oncology Centre
Groenkloof, 0181, South Africa
Hopelands Cancer Centre
Hilton, 3245, South Africa
Cancercare
Port Elizabeth, 6045, South Africa
University of Pretoria; Department of Medical Oncology
Pretoria, 0002, South Africa
National Cancer Centre
Gyeonggi-do, 10408, South Korea
Seoul National University Bundang Hospital
Gyeonggi-do, 13620, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Severance Hospital, Yonsei University Health System; Pharmacy
Seoul, 03722, South Korea
Asan Medical Center.
Seoul, 138-736, South Korea
Samsung Medical Center
Seoul, 6351, South Korea
CI Cherkasy Regional Oncological Dispensary of Cherkasy RC RC of Clinical Oncology
Cherkassy, 18009, Ukraine
CI Dnipropetrovsk CMCH 4 of Dnipropetrovsk RC Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU
Dnipropetrovsk, 49102, Ukraine
CCTPI Donetsk Regional Antitumor Center
Donetsk, 83092, Ukraine
Kyiv Сity Clinical Oncological Center
Kyiv, 03115, Ukraine
Medical and Prophylactic Institution Volyn Regional Oncological Dispensary
Lutsk, 63000, Ukraine
Lviv State Oncological Regional Treatment and Diagnostic Center
Lviv, 79031, Ukraine
RCI Sumy Regional Clinical Oncological Dispensary
Sumy, 40005, Ukraine
CCCH City Oncological Center SHEI Uzhgorod NU
Uzhhorod, 88000, Ukraine
Velindre Cancer Centre
Cardiff, CF14 2TL, United Kingdom
Western General Hospital
Edinburgh, EH4 2XU, United Kingdom
Royal Devon and Exeter Hospital (Wonford)
Exeter, EX2 5DW, United Kingdom
Mount Vernon Hospital
Middlesex, HA6 2RN, United Kingdom
Peterborough City Hospital
Peterborough, PE3 9GZ, United Kingdom
Derriford Hospital; Clinical Neurology Research Group
Plymouth, PL6 8BX, United Kingdom
Related Publications (2)
Masuda N, Takahashi M, Nakagami K, Okumura Y, Nakayama T, Sato N, Kanatani K, Tajima K, Kashiwaba M. First-line bevacizumab plus paclitaxel in Japanese patients with HER2-negative metastatic breast cancer: subgroup results from the randomized Phase III MERiDiAN trial. Jpn J Clin Oncol. 2017 May 1;47(5):385-392. doi: 10.1093/jjco/hyx001.
PMID: 28158579DERIVEDMiles D, Cameron D, Bondarenko I, Manzyuk L, Alcedo JC, Lopez RI, Im SA, Canon JL, Shparyk Y, Yardley DA, Masuda N, Ro J, Denduluri N, Hubeaux S, Quah C, Bais C, O'Shaughnessy J. Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation. Eur J Cancer. 2017 Jan;70:146-155. doi: 10.1016/j.ejca.2016.09.024. Epub 2016 Nov 4.
PMID: 27817944DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-LaRoche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
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
August 9, 2012
First Posted
August 13, 2012
Study Start
August 27, 2012
Primary Completion
November 30, 2014
Study Completion
November 21, 2017
Last Updated
January 22, 2019
Results First Posted
February 10, 2016
Record last verified: 2019-01