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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Bevacizumab [Avastin]; Drug: Paclitaxel; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 481
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma Buenos Aires, Argentina, C1284AEB
    • Hospital Britanico de Buenos Aires
  • La Rioja, Argentina, F5300COE
    • Centro Oncologico Riojano Integral (CORI)
  • Pergamino, Argentina, B2700CPM
    • Centro de Investigacion Pergamino SA
  • Quilmes, Argentina, 1878
    • Instituto De Investigaciones Clinicas Quilmes
  • Rosario, Argentina, S2000KZE
    • Instituto de Oncología de Rosario
  • Rosario, Argentina, 2000
    • Hospital Provincial del Centenario
  • Rosario, Argentina, S2000CVB
    • Instituto CAICI
  • Rosario, Santa FE, Argentina, S2000DSV
    • Sanatorio Parque S.A.
  • Santa Fe, Argentina, 03000
    • ISIS Clinica Especializada
• Belgium
  • Brasschaat, Belgium, 2930
    • AZ Klina
  • Brussel, Belgium, 1090
    • UZ Brussel
  • Edegem, Belgium, 2650
    • UZ Antwerpen
  • Gilly (Charleroi), Belgium, 6000
    • GHdC Site Saint-Joseph
  • Mons, Belgium, 7000
    • CHU Ambroise Paré; Hematology and Oncology Department
• Brazil
  • DF
    • Brasilia, DF, Brazil, 70390-055
      • Clinica de Tratamento e Pesquisa Oncologica - Oncotek
  • RS
    • Passo Fundo, RS, Brazil, 99010-260
      • Hospital da Cidade de Passo Fundo; Centro de Pesquisa em Oncologia
    • Porto Alegre, RS, Brazil, 91350-200
      • Hospital Nossa Senhora da Conceição
    • Porto Alegre, RS, Brazil, 90430-090
      • Clinica de Oncologia de Porto Alegre - CliniOnco
    • Porto Alegre, RS, Brazil, 90110-270
      • Hospital Sao Lucas - PUCRS; Pesquisa Clinica
  • SC
    • Florianopolis, SC, Brazil, 88034-000
      • Centro de Pesquisas Oncológicas - CEPON
    • Itajai, SC, Brazil, 88301-220
      • Clinica de Neoplasias Litoral
  • SP
    • Ribeirao Preto, SP, Brazil, 14048-900
      • Hospital das Clinicas - FMUSP Ribeirao Preto
    • Sao Paulo, SP, Brazil, 22793-080
      • Universidade Federal de São Paulo - UNIFESP
• Bulgaria
  • Gabrovo, Bulgaria, 5300
    • Mhat Dr. Tota Venkova Ad
  • Haskovo, Bulgaria, 6300
    • SHATOD Haskovo EOOD
  • Plovdiv, Bulgaria, 4004
    • Complex Oncological Center - Plovdiv, EOOD
  • Shumen, Bulgaria, 9700
    • Complex Oncological Center - Shumen, EOOD; Department of Chemotherapy
  • Sofia, Bulgaria, 1233
    • SHATOD - Sofia District, EOOD
  • Sofia, Bulgaria, 1303
    • MHAT Serdika, EOOD
  • Sofia, Bulgaria, 1527
    • UMHAT Tsaritsa Yoanna - ISUL, EAD
  • Sofia, Bulgaria, 1784
    • SHATOD - Sofia City, EOOD
  • Varna, Bulgaria, 9010
    • SHATOD Dr. Marko Antonov Markov-Varna, EOOD
  • Veliko Tarnovo, Bulgaria, 5000
    • COC - Veliko Tarnovo
• Chile
  • Santiago, Chile, 7500921
    • Fundacion Arturo Lopez Perez
  • Santiago, Chile, 7500921
    • Centro de Estudios Oncologicos de Santiago (CEOS) Oncologia
  • Santiago, Chile, 8380000
    • Instituto Nacional del Cancer
  • Viña del Mar, Chile
    • Instituto Oncologico Ltda.
• Germany
  • Aschaffenburg, Germany, 63739
    • Studienzentrum Aschaffenburg
  • Dortmund, Germany, 44137
    • St. Johannes Hospital; Klinik fuer innere Medizin II, Onkologie, Haematologie
  • Goch, Germany, 47574
    • Wilhelm-Anton-Hospital gGmbH
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg
  • Köln, Germany, 50935
    • St. Elisabeth-Krankenhaus
  • Ulm, Germany, 89081
    • Universitaetsklinikum Ulm
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Azienda Ospedaliera A. Cardarelli
  • Emilia-Romagna
    • Rimini, Emilia-Romagna, Italy, 47923
      • Ospedale Degli Infermi
  • Lombardia
    • Legnago (VR), Lombardia, Italy, 37045
      • Ospedale Mater Salutis
    • Milano, Lombardia, Italy, 20132
      • Ospedale San Raffaele
    • Pavia, Lombardia, Italy, 27100
      • Fondazione Salvatore Maugeri IRCCS
  • Puglia
    • San Giovanni Rotondo, Puglia, Italy, 71013
      • Ospedale Casa Sollievo Della Sofferenza IRCCS
  • Toscana
    • Lido Di Camaiore, Toscana, Italy, 55043
      • Ospedale Versilia
• Japan
  • Ehime, Japan, 791-0280
    • NHO Shikoku Cancer Center; Dept of Respiratory Medicine
  • Fukuoka, Japan, 811-1395
    • NHO Kyushu Cancer Center
  • Gifu, Japan, 501-1194
    • Gifu University Hospital
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital
  • Hyogo, Japan, 663-8501
    • Hyogo College of Medicine Hospital
  • Iwate, Japan, 020-8505
    • Iwate Medical University Hospital
  • Kagoshima, Japan, 892-0833
    • Hakuaikai Sagara Hospital
  • Kanagawa, Japan, 259-1193
    • Tokai University Hospital
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital
  • Kumamoto, Japan, 862-8505
    • Kumamoto City Hospital
  • Miyagi, Japan, 980-8574
    • Tohoku University Hospital
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital
  • Osaka, Japan, 589-8511
    • Kindai University Hospital
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute
  • Osaka, Japan, 540-0006
    • NHO Osaka National Hospital
  • Sapporo-shi, Japan, 003-0804
    • Nho Hokkaido Cancer Center
  • Shizuoka-shi, Japan, 420-8527
    • Shizuoka General Hospital
  • Tokyo, Japan, 105-8470
    • Toranomon Hospital
  • Tokyo, Japan, 113-8431
    • Juntendo University Hospital
  • Tokyo, Japan, 113-8677
    • Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 10408
    • National Cancer Centre
  • Gyeonggi-do, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 6351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center.
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System; Pharmacy
• Panama
  • Panama, Panama, 0832
    • Centro Hemato Oncologico Panama
  • Panama, Panama
    • Medical Research Centre
• Romania
  • Bucuresti, Romania, 022328
    • Institutul Oncologic "Prof. Dr. Al. Trestioreanu"
  • Cluj-Napoca, Romania, 400058
    • Medisprof srl
  • Cluj-Napoca, Romania, 400015
    • Institutul Oncologic Prof. Dr. Ion Chiricuta Cluj-Napoca; Radioterapie I - Oncologie
  • Timisoara, Romania, 300239
    • Oncomed Srl
• Russian Federation
  • Chernihiv, Russian Federation, 14029
    • CTPI Chernihiv Regional Oncological Dispensary
  • Kazan, Russian Federation, 420029
    • SHI Republican Clinical Oncological Dispensary of HM RT
  • Krasnodar, Russian Federation, 350040
    • Regional Clinical Oncology Dispensary
  • Moscow, Russian Federation, 115478
    • FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
  • Saint-Petersburg, Russian Federation
    • FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"
  • Saint-Petersburg, Russian Federation, 197022
    • City Clinical Oncology Dispensary
  • Saint-Petersburg, Russian Federation, 197101
    • SBEIHPE SSMU n.a. I.P.Pavlov of MOH and SD of RF
  • Samara, Russian Federation, 443031
    • Samara Regional Oncology Dispensary
  • St. Petersburg, Russian Federation, 195271
    • Non-state Healthcare Institution "Road Clinical Hospital of JSC Russian Railways"
• South Africa
  • Bloemfontein, South Africa, 9301
    • National Hospital; Oncotherapy Dept
  • Cape Town, South Africa, 7570
    • Cape Town Oncology Trials
  • Durban, South Africa, 4091
    • Hopelands Cancer Centre Durban
  • Groenkloof, South Africa, 0181
    • Mary Potter Oncology Centre
  • Hilton, South Africa, 3245
    • Hopelands Cancer Centre
  • Port Elizabeth, South Africa, 6045
    • Cancercare
  • Pretoria, South Africa, 0002
    • University of Pretoria; Department of Medical Oncology
• Ukraine
  • Cherkassy, Ukraine, 18009
    • CI Cherkasy Regional Oncological Dispensary of Cherkasy RC RC of Clinical Oncology
  • Dnipropetrovsk, Ukraine, 49102
    • CI Dnipropetrovsk CMCH 4 of Dnipropetrovsk RC Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU
  • Donetsk, Ukraine, 83092
    • CCTPI Donetsk Regional Antitumor Center
  • Kyiv, Ukraine, 03115
    • Kyiv Сity Clinical Oncological Center
  • Lutsk, Ukraine, 63000
    • Medical and Prophylactic Institution Volyn Regional Oncological Dispensary
  • Lviv, Ukraine, 79031
    • Lviv State Oncological Regional Treatment and Diagnostic Center
  • Sumy, Ukraine, 40005
    • RCI Sumy Regional Clinical Oncological Dispensary
  • Uzhgorod, Ukraine, 88000
    • CCCH City Oncological Center SHEI Uzhgorod NU
• United Kingdom
  • Cardiff, United Kingdom, CF14 2TL
    • Velindre Cancer Centre
  • Edinburgh, United Kingdom, EH4 2XU
    • Western General Hospital
  • Exeter, United Kingdom, EX2 5DW
    • Royal Devon and Exeter Hospital (Wonford)
  • Middlesex, United Kingdom, HA6 2RN
    • Mount Vernon Hospital
  • Peterborough, United Kingdom, PE3 9GZ
    • Peterborough City Hospital
  • Plymouth, United Kingdom, PL6 8BX
    • Derriford Hospital; Clinical Neurology Research Group
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center
  • California
    • Corona, California, United States, 92879
      • Wilshire Oncology Medical Group
    • Glendora, California, United States, 91741
      • Wilshire Oncology Medical Group
    • La Verne, California, United States, 91750
      • Wilshire Oncology Medical Group
    • Long Beach, California, United States, 90806
      • Long Beach Memorial Medical Center; Oncology
    • Palm Springs, California, United States, 92262
      • Tenet Health System Desert Inc
    • Pomona, California, United States, 91767
      • Wilshire Oncology Medical Group; Oncology
    • Rancho Cucamonga, California, United States, 91730
      • Wilshire Oncology Medical Group
    • West Covina, California, United States, 91790
      • Wilshire Oncology Medical Group
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital
  • Florida
    • Deerfield Beach, Florida, United States, 33442
      • Sylvester Comprehensive Cancer Center - Deerfield Beach; Sylvester Cancer Center
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists - Broadway
    • Plantation, Florida, United States, 33322
      • BRCR Medical Center, Inc.
    • Port Saint Lucie, Florida, United States, 34952
      • Hematology Oncology Associates of the Treasure Coast
  • Georgia
    • Athens, Georgia, United States, 30607
      • Northeast Georgia Cancer Care LLC
    • Atlanta, Georgia, United States, 30318
      • Peachtree Hematology & Oncology Consultants, Pc
  • Hawaii
    • Honolulu, Hawaii, United States, 96819
      • Kaiser Foundation Hospital; Dr. Eron's Office
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • IU Cancer Pavilion
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
    • Columbia, Maryland, United States, 21044
      • Maryland Oncology Hematology, P.A.
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic Inc. - PARENT ACCOUNT
  • Mississippi
    • New Albany, Mississippi, United States, 38652
      • The Jones Clinic, PC
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Missouri Cancer Associates
    • Saint Louis, Missouri, United States, 63110
      • Washington University; Center for Adv Medicine
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • Ohio
    • Middletown, Ohio, United States, 45042
      • Signal Point Clinical; Research Center, LLC
    • Sylvania, Ohio, United States, 43560
      • ProMedica Hickman Cancer Center at Flower Hospital; Hickman Cancer Center
    • Toledo, Ohio, United States, 43614
      • University of Toledo; Dept. of Medicine
  • Pennsylvania
    • Leesburg, Pennsylvania, United States, 20176
      • Virginia Cancer Specialists - Leesburg
    • Philadelphia, Pennsylvania, United States, 19106
      • Pennsylvania Oncology Hematology Associates, Inc.; PA Oncology & Hematology
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina; Division of Hematology-Oncology
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • SCRI-Tennessee Oncology
  • Texas
    • Dallas, Texas, United States, 75230
      • Texas Oncology-Medical City Dallas
    • Dallas, Texas, United States, 75231
      • Texas Oncology, P.A. - Dallas Presbyterian
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology, P.A. - Fort Worth
    • Fort Worth, Texas, United States, 76132
      • Texas Oncology- Southwest Fort Worth
    • Galveston, Texas, United States, 77555
      • Univ of Texas Medical Branch
    • Garland, Texas, United States, 77060
      • Texas Oncology, P.A. - Garland
    • Kerrville, Texas, United States, 78028
      • Cancer Care Centers of S Texas
    • Longview, Texas, United States, 75601
      • Texas Oncology- Longview Cancer Center
    • McAllen, Texas, United States, 78503
      • Texas Oncology, P.A. - McAllen; South Texas Cancer Center-McAllen
    • Plano, Texas, United States, 75093
      • Texas Oncology Plano West
    • San Antonio, Texas, United States, 78217
      • Cancer Care Centers of South Texas
    • San Antonio, Texas, United States, 78212
      • Cancer Care Centers of South Texas
    • San Antonio, Texas, United States, 78258
      • CancerCare Centers of South Texas
    • The Woodlands, Texas, United States, 77060
      • Texas Oncology, P.A. - Tyler
    • The Woodlands, Texas, United States, 77060
      • Texas Oncology, P.A.
  • Virginia
    • Alexandria, Virginia, United States, 22304
      • Virginia Cancer Specialists - Alexandria
    • Arlington, Virginia, United States, 22205
      • Fairfax Northern Virginia Hematology-Oncology PC
    • Bristol, Virginia, United States, 24201
      • Wellmonth Physician Services
    • Chesapeake, Virginia, United States, 23320
      • Virginia Oncology Associates - Chesapeake
    • Christiansburg, Virginia, United States, 24073
      • Oncology & Hematology Associates of SW Va Inc. - Market Street
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, PC
    • Fredericksburg, Virginia, United States, 22408
      • Hematology Oncology Associates of Fredericksburg, Inc.
    • Gainesville, Virginia, United States, 20155
      • Virginia Cancer Specialists - Gainsville
    • Hampton, Virginia, United States, 23666
      • Virginia Oncology Associates - Hampton
    • Low Moor, Virginia, United States, 24457
      • Oncology and Hematology Assoc. of SW VA, Inc. - Low Moor
    • Newport News, Virginia, United States, 23606
      • Virginia Oncology Associates - New Port News
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates
    • Roanoke, Virginia, United States, 24014
      • Oncology & Hematolgy Associates of SW Va Inc. - Roanoke
    • Salem, Virginia, United States, 77060
      • Oncology and Hematology Assoc. of SW VA, Inc.
    • Virginia Beach, Virginia, United States, 23456
      • Virginia Oncology Associates - Virginia Beach
    • Wytheville, Virginia, United States, 24382
      • Oncology and Hematology Assoc. of SW VA, Inc. - Wytheville
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties, PLLC; Research Department
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University; Endocrinology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Paclitaxel + Bevacizumab [Avastin]	Drug: Bevacizumab [Avastin]; Intravenous repeating dose; Drug: Paclitaxel; Intravenous repeating dose
Experimental: B; Paclitaxel + Placebo	Drug: Paclitaxel; Intravenous repeating dose; Drug: Placebo; Intravenous repeating dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Died - ITT Population		From randomization till death or clinical cut-off (up to 244 weeks)
Overall Survival (OS) - ITT Population	OS was defined as the interval between the date of randomization and death from any cause. OS was estimated using Kaplan Meier method.	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	OS was defined as the interval between the date of randomization and death from any cause. OS was estimated using Kaplan Meier method.	From randomization till death or clinical cut-off (up to 244 weeks)
Percentage of Participants With an Objective Response - ITT Population	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).	Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 117.7 weeks)
Percentage of Participants With an Objective Response - High Baseline Plasma VEGF-A ITT Population	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.	Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 111.3 weeks)
Duration of Response - ITT Population	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.	Baseline, every 8 weeks until documented disease progression or clinical cut-off (up to 117.7 weeks)
Duration of Response - High Baseline Plasma VEGF-A ITT Population	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.	Baseline, every 8 weeks until documented disease progression or clinical cut-off (up to 111.3 weeks)
Percentage of Participants Who Were Alive at 1 Year - ITT Population		1 year
Secondary: Percentage of Participants Who Were Alive at 1 Year - High Baseline Plasma VEGF-A ITT Population		1 year

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• 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.
• Miles 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2012
• Primary Completion (Actual): November 30, 2014
• Study Completion (Actual): November 21, 2017

Study Registration Dates

• First Submitted: August 9, 2012
• First Submitted That Met QC Criteria: August 9, 2012
• First Posted (Estimate): August 13, 2012

Study Record Updates

• Last Update Posted (Actual): January 22, 2019
• Last Update Submitted That Met QC Criteria: January 7, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Paclitaxel; Bevacizumab
• Other Study ID Numbers: GO25632; 2011-005335-97 (EudraCT Number)