Clinical trial NCT01663727: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-08-13
Enrollment: 481
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Progression or Death in Intent-to-Treat (ITT) Population
timeFrame: Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 117.7 weeks)
measure: Progression Free Survival (PFS) in ITT Population
timeFrame: Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 117.7 weeks)
measure: Percentage of Participants With Progression or Death in High Baseline Plasma Vascular Endothelial Growth Factor-A (VEGF-A) ITT Population
timeFrame: Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 111.3 weeks)
measure: PFS in High Baseline Plasma VEGF-A ITT Population
timeFrame: Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 111.3 weeks)
Secondary outcomes:
measure: Percentage of Participants Who Died - ITT Population
timeFrame: From randomization till death or clinical cut-off (up to 244 weeks)
measure: Overall Survival (OS) - ITT Population
timeFrame: From randomization till death or clinical cut-off (up to 244 weeks)
measure: Percentage of Participants Who Died - High Baseline Plasma VEGF-A ITT Population
timeFrame: From randomization till death or clinical cut-off (up to 244 weeks)
measure: OS - High Baseline Plasma VEGF-A ITT Population
timeFrame: From randomization till death or clinical cut-off (up to 244 weeks)
measure: Percentage of Participants With an Objective Response - ITT Population
timeFrame: Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 117.7 weeks)
measure: Percentage of Participants With an Objective Response - High Baseline Plasma VEGF-A ITT Population
timeFrame: Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 111.3 weeks)
measure: Duration of Response - ITT Population
timeFrame: Baseline, every 8 weeks until documented disease progression or clinical cut-off (up to 117.7 weeks)
measure: Duration of Response - High Baseline Plasma VEGF-A ITT Population
timeFrame: Baseline, every 8 weeks until documented disease progression or clinical cut-off (up to 111.3 weeks)
measure: Percentage of Participants Who Were Alive at 1 Year - ITT Population
timeFrame: 1 year
measure: Secondary: Percentage of Participants Who Were Alive at 1 Year - High Baseline Plasma VEGF-A ITT Population
timeFrame: 1 year
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Corona
country: United States
facility: Wilshire Oncology Medical Group
state: California
city: Glendora
country: United States
facility: Wilshire Oncology Medical Group
state: California
city: La Verne
country: United States
facility: Wilshire Oncology Medical Group
state: California
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center; Oncology
state: California
city: Palm Springs
country: United States
facility: Tenet Health System Desert Inc
state: California
city: Pomona
country: United States
facility: Wilshire Oncology Medical Group; Oncology
state: California
city: Rancho Cucamonga
country: United States
facility: Wilshire Oncology Medical Group
state: California
city: West Covina
country: United States
facility: Wilshire Oncology Medical Group
state: California
city: Washington
country: United States
facility: Washington Hospital
state: District of Columbia
city: Deerfield Beach
country: United States
facility: Sylvester Comprehensive Cancer Center - Deerfield Beach; Sylvester Cancer Center
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - Broadway
state: Florida
city: Plantation
country: United States
facility: BRCR Medical Center, Inc.
state: Florida
city: Port Saint Lucie
country: United States
facility: Hematology Oncology Associates of the Treasure Coast
state: Florida
city: Athens
country: United States
facility: Northeast Georgia Cancer Care LLC
state: Georgia
city: Atlanta
country: United States
facility: Peachtree Hematology & Oncology Consultants, Pc
state: Georgia
city: Honolulu
country: United States
facility: Kaiser Foundation Hospital; Dr. Eron's Office
state: Hawaii
city: Indianapolis
country: United States
facility: IU Cancer Pavilion
state: Indiana
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Columbia
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Burlington
country: United States
facility: Lahey Clinic Inc. - PARENT ACCOUNT
state: Massachusetts
city: New Albany
country: United States
facility: The Jones Clinic, PC
state: Mississippi
city: Columbia
country: United States
facility: Missouri Cancer Associates
state: Missouri
city: Saint Louis
country: United States
facility: Washington University; Center for Adv Medicine
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Middletown
country: United States
facility: Signal Point Clinical; Research Center, LLC
state: Ohio
city: Sylvania
country: United States
facility: ProMedica Hickman Cancer Center at Flower Hospital; Hickman Cancer Center
state: Ohio
city: Toledo
country: United States
facility: University of Toledo; Dept. of Medicine
state: Ohio
city: Leesburg
country: United States
facility: Virginia Cancer Specialists - Leesburg
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Oncology Hematology Associates, Inc.; PA Oncology & Hematology
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina; Division of Hematology-Oncology
state: South Carolina
city: Nashville
country: United States
facility: SCRI-Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology-Medical City Dallas
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A. - Dallas Presbyterian
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology, P.A. - Fort Worth
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology- Southwest Fort Worth
state: Texas
city: Galveston
country: United States
facility: Univ of Texas Medical Branch
state: Texas
city: Garland
country: United States
facility: Texas Oncology, P.A. - Garland
state: Texas
city: Kerrville
country: United States
facility: Cancer Care Centers of S Texas
state: Texas
city: Longview
country: United States
facility: Texas Oncology- Longview Cancer Center
state: Texas
city: McAllen
country: United States
facility: Texas Oncology, P.A. - McAllen; South Texas Cancer Center-McAllen
state: Texas
city: Plano
country: United States
facility: Texas Oncology Plano West
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas
state: Texas
city: San Antonio
country: United States
facility: CancerCare Centers of South Texas
state: Texas
city: The Woodlands
country: United States
facility: Texas Oncology, P.A. - Tyler
state: Texas
city: The Woodlands
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Alexandria
country: United States
facility: Virginia Cancer Specialists - Alexandria
state: Virginia
city: Arlington
country: United States
facility: Fairfax Northern Virginia Hematology-Oncology PC
state: Virginia
city: Bristol
country: United States
facility: Wellmonth Physician Services
state: Virginia
city: Chesapeake
country: United States
facility: Virginia Oncology Associates - Chesapeake
state: Virginia
city: Christiansburg
country: United States
facility: Oncology & Hematology Associates of SW Va Inc. - Market Street
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Fredericksburg
country: United States
facility: Hematology Oncology Associates of Fredericksburg, Inc.
state: Virginia
city: Gainesville
country: United States
facility: Virginia Cancer Specialists - Gainsville
state: Virginia
city: Hampton
country: United States
facility: Virginia Oncology Associates - Hampton
state: Virginia
city: Low Moor
country: United States
facility: Oncology and Hematology Assoc. of SW VA, Inc. - Low Moor
state: Virginia
city: Newport News
country: United States
facility: Virginia Oncology Associates - New Port News
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Roanoke
country: United States
facility: Oncology & Hematolgy Associates of SW Va Inc. - Roanoke
state: Virginia
city: Salem
country: United States
facility: Oncology and Hematology Assoc. of SW VA, Inc.
state: Virginia
city: Virginia Beach
country: United States
facility: Virginia Oncology Associates - Virginia Beach
state: Virginia
city: Wytheville
country: United States
facility: Oncology and Hematology Assoc. of SW VA, Inc. - Wytheville
state: Virginia
city: Tacoma
country: United States
facility: Northwest Medical Specialties, PLLC; Research Department
state: Washington
city: Morgantown
country: United States
facility: West Virginia University; Endocrinology
state: West Virginia
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: La Rioja
country: Argentina
facility: Centro Oncologico Riojano Integral (CORI)
city: Pergamino
country: Argentina
facility: Centro de Investigacion Pergamino SA
city: Quilmes
country: Argentina
facility: Instituto de Investigaciones Clínicas Quilmes
city: Rosario, Santa FE
country: Argentina
facility: Sanatorio Parque S.A.
city: Rosario
country: Argentina
facility: Hospital Provincial del Centenario
city: Rosario
country: Argentina
facility: Instituto CAICI
city: Rosario
country: Argentina
facility: Instituto de Oncología de Rosario
city: Santa Fe
country: Argentina
facility: ISIS Clinica Especializada
city: Brasschaat
country: Belgium
facility: AZ KLINA
city: Brussel
country: Belgium
facility: UZ Brussel
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gilly (Charleroi)
country: Belgium
facility: GHdC Site Saint-Joseph
city: Mons
country: Belgium
facility: CHU Ambroise Paré; Hematology and Oncology Department
city: Brasilia
country: Brazil
facility: Clinica de Tratamento e Pesquisa Oncologica - Oncotek
state: DF
city: Passo Fundo
country: Brazil
facility: Hospital da Cidade de Passo Fundo; Centro de Pesquisa em Oncologia
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas - PUCRS; Pesquisa Clinica
state: RS
city: Porto Alegre
country: Brazil
facility: Clinica de Oncologia de Porto Alegre - CliniOnco
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao
state: RS
city: Florianopolis
country: Brazil
facility: Centro de Pesquisas Oncologicas - CEPON
state: SC
city: Itajai
country: Brazil
facility: Clinica de Neoplasias Litoral
state: SC
city: Ribeirao Preto
country: Brazil
facility: Hospital das Clinicas - FMUSP Ribeirao Preto
state: SP
city: Sao Paulo
country: Brazil
facility: Universidade Federal de Sao Paulo - UNIFESP
state: SP
city: Gabrovo
country: Bulgaria
facility: MHAT Dr. Tota Venkova AD
city: Haskovo
country: Bulgaria
facility: SHATOD Haskovo EOOD
city: Plovdiv
country: Bulgaria
facility: Complex Oncological Center - Plovdiv, EOOD
city: Shumen
country: Bulgaria
facility: Complex Oncological Center - Shumen, EOOD; Department of Chemotherapy
city: Sofia
country: Bulgaria
facility: SHATOD - Sofia District, EOOD
city: Sofia
country: Bulgaria
facility: MHAT Serdika, EOOD
city: Sofia
country: Bulgaria
facility: UMHAT Tsaritsa Yoanna - ISUL, EAD
city: Sofia
country: Bulgaria
facility: SHATOD - Sofia City, EOOD
city: Varna
country: Bulgaria
facility: SHATOD Dr. Marko Antonov Markov-Varna, EOOD
city: Veliko Tarnovo
country: Bulgaria
facility: COC - Veliko Tarnovo
city: Santiago
country: Chile
facility: Centro de Estudios Oncologicos de Santiago (CEOS) Oncologia
city: Santiago
country: Chile
facility: Fundacion Arturo Lopez Perez
city: Santiago
country: Chile
facility: Instituto Nacional del Cancer
city: Viña del Mar
country: Chile
facility: Instituto Oncologico Ltda.
city: Aschaffenburg
country: Germany
facility: Studienzentrum Aschaffenburg
city: Dortmund
country: Germany
facility: St. Johannes Hospital; Klinik fuer innere Medizin II, Onkologie, Haematologie
city: Goch
country: Germany
facility: Wilhelm-Anton-Hospital gGmbH
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Köln
country: Germany
facility: St. Elisabeth-Krankenhaus
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Napoli
country: Italy
facility: Azienda Ospedaliera A. Cardarelli
state: Campania
city: Rimini
country: Italy
facility: Ospedale degli Infermi
state: Emilia-Romagna
city: Legnago (VR)
country: Italy
facility: Ospedale Mater Salutis
state: Lombardia
city: Milano
country: Italy
facility: Ospedale San Raffaele
state: Lombardia
city: Pavia
country: Italy
facility: Fondazione Salvatore Maugeri IRCCS
state: Lombardia
city: San Giovanni Rotondo
country: Italy
facility: Ospedale Casa Sollievo Della Sofferenza IRCCS
state: Puglia
city: Lido Di Camaiore
country: Italy
facility: Ospedale Versilia
state: Toscana
city: Ehime
country: Japan
facility: NHO Shikoku Cancer Center; Dept of Respiratory Medicine
city: Fukuoka
country: Japan
facility: NHO Kyushu Cancer Center
city: Gifu
country: Japan
facility: Gifu University Hospital
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Hyogo
country: Japan
facility: Hyogo College of Medicine Hospital
city: Iwate
country: Japan
facility: Iwate Medical University Hospital
city: Kagoshima
country: Japan
facility: Hakuaikai Sagara Hospital
city: Kanagawa
country: Japan
facility: Tokai University Hospital
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Kumamoto
country: Japan
facility: Kumamoto City Hospital
city: Miyagi
country: Japan
facility: Tohoku University Hospital
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Osaka
country: Japan
facility: NHO Osaka National Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Osaka
country: Japan
facility: Kindai University Hospital
city: Sapporo-shi
country: Japan
facility: NHO Hokkaido Cancer Center
city: Shizuoka-shi
country: Japan
facility: Shizuoka General Hospital
city: Tokyo
country: Japan
facility: Toranomon Hospital
city: Tokyo
country: Japan
facility: Juntendo University Hospital
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Centre
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System; Pharmacy
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center.
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Panama
country: Panama
facility: Centro Hemato Oncologico Panama
city: Panama
country: Panama
facility: Medical Research Centre
city: Bucuresti
country: Romania
facility: Institutul Oncologic "Prof. Dr. Al. Trestioreanu"
city: Cluj-Napoca
country: Romania
facility: Institutul Oncologic Prof. Dr. Ion Chiricuta Cluj-Napoca; Radioterapie I - Oncologie
city: Cluj-Napoca
country: Romania
facility: Medisprof SRL
city: Timisoara
country: Romania
facility: Oncomed SRL
city: Chernihiv
country: Russian Federation
facility: CTPI Chernihiv Regional Oncological Dispensary
city: Kazan
country: Russian Federation
facility: SHI Republican Clinical Oncological Dispensary of HM RT
city: Krasnodar
country: Russian Federation
facility: Regional Clinical Oncology Dispensary
city: Moscow
country: Russian Federation
facility: FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
city: Saint-Petersburg
country: Russian Federation
facility: City Clinical Oncology Dispensary
city: Saint-Petersburg
country: Russian Federation
facility: SBEIHPE SSMU n.a. I.P.Pavlov of MOH and SD of RF
city: Saint-Petersburg
country: Russian Federation
facility: FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"
city: Samara
country: Russian Federation
facility: Samara Regional Oncology Dispensary
city: St. Petersburg
country: Russian Federation
facility: Non-state Healthcare Institution "Road Clinical Hospital of JSC Russian Railways"
city: Bloemfontein
country: South Africa
facility: National Hospital; Oncotherapy Dept
city: Cape Town
country: South Africa
facility: Cape Town Oncology Trials
city: Durban
country: South Africa
facility: Hopelands Cancer Centre Durban
city: Groenkloof
country: South Africa
facility: Mary Potter Oncology Centre
city: Hilton
country: South Africa
facility: Hopelands Cancer Centre
city: Port Elizabeth
country: South Africa
facility: Cancercare
city: Pretoria
country: South Africa
facility: University of Pretoria; Department of Medical Oncology
city: Cherkassy
country: Ukraine
facility: CI Cherkasy Regional Oncological Dispensary of Cherkasy RC RC of Clinical Oncology
city: Dnipropetrovsk
country: Ukraine
facility: CI Dnipropetrovsk CMCH 4 of Dnipropetrovsk RC Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU
city: Donetsk
country: Ukraine
facility: CCTPI Donetsk Regional Antitumor Center
city: Kyiv
country: Ukraine
facility: Kyiv Сity Clinical Oncological Center
city: Lutsk
country: Ukraine
facility: Medical and Prophylactic Institution Volyn Regional Oncological Dispensary
city: Lviv
country: Ukraine
facility: Lviv State Oncological Regional Treatment and Diagnostic Center
city: Sumy
country: Ukraine
facility: RCI Sumy Regional Clinical Oncological Dispensary
city: Uzhgorod
country: Ukraine
facility: CCCH City Oncological Center SHEI Uzhgorod NU
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital (Wonford)
city: Middlesex
country: United Kingdom
facility: Mount Vernon Hospital
city: Peterborough
country: United Kingdom
facility: Peterborough City Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital; Clinical Neurology Research Group
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.