BETH Study: Treatment of HER2 Positive Breast Cancer With Chemotherapy Plus Trastuzumab vs Chemotherapy Plus Trastuzumab Plus Bevacizumab (BETH)
Breast Cancer

About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring HER2 positive breast cancer, invasive breast cancer, bevacizumab, NSABP, Roche, CIRG, trastuzumab, cyclophosphamide, docetaxel, carboplatin, 5-fluorouracil, epirubicin
Eligibility Criteria
Inclusion Criteria:
- Life expectancy of at least 10 years, excluding their diagnosis of breast cancer.
- Women who have had breast reconstruction utilizing tissue expanders must be in agreement with delaying surgery to replace the tissue expanders with permanent implants until 3 months following the last dose of bevacizumab
- Women of reproductive potential must agree to use an effective non-hormonal method of contraception (for example condoms, some intrauterine devices, diaphragms, vasectomized partner, or abstinence) during therapy and for at least 6 months after the last dose of bevacizumab and/or trastuzumab.
- Submission of tumor samples from the breast surgery for central HER2 testing is required for all patients prior to enrollment in the BETH Trial
- Signed and dated IRB/EC-approved consent
- ECOG performance status of 0 or 1
- The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination.
- The breast cancer must be HER2-positive based on test results as follows: Local testing (if available) should demonstrate that the tumor is IHC 2+ or 3+ or is considered to be HER2-positive for gene amplification by FISH, CISH, or other in situ hybridization (ISH) method. If local ISH test results are considered equivocal, the tumor can be submitted for central HER2 testing. (If local testing is not possible, the tumor can be submitted for central HER2 testing.) Central testing (a requirement for ALL patients) must demonstrate that the tumor is HER2-positive which is defined as FISH-positive and/or IHC 3+.
- All of the following staging criteria (according to the 6th edition of the AJCC Cancer Staging Manual) must be met: By pathologic evaluation, primary tumor must be pT1-3; By pathologic evaluation, ipsilateral nodes must be pN0, pN1 (pN1mi, pN1a, pN1b, pN1c), pN2a, pN3a, or pN3b. If pN0, at least one of the following criteria must be met: Pathologic tumor size > 2.0 cm; ER negative and PgR negative; Histologic and/or nuclear grade 2 (intermediate) or 3 (high); or Age < 35 years
- Patients must have undergone either a total mastectomy or breast conserving surgery (lumpectomy).
- For patients who undergo lumpectomy, the margins of the resected specimen must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional operative procedures may be performed to obtain clear margins. If tumor is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible. (Patients with margins positive for lobular carcinoma in situ [LCIS] are eligible without additional resection.)
- For patients who undergo mastectomy, margins must be free of gross residual tumor. Patients with microscopic positive margins are eligible.
- Patients must have completed one of the following procedures for evaluation of pathologic nodal status: Sentinel lymphadenectomy followed by removal of additional non-sentinel lymph nodes if the sentinel node (SN) is positive; Sentinel lymphadenectomy alone if pathologic nodal staging based on sentinel lymphadenectomy is pN0, pN1mi or pN1b; or Axillary lymphadenectomy without SN isolation procedure.
- The interval between the last surgery for breast cancer (treatment or staging) and randomization must be at least 28 days but no more than 84 days.
- Patients must have ER analysis performed on the primary tumor prior to randomization. If ER analysis is negative, then PgR analysis must also be performed.
- The most recent postoperative blood counts, performed within 6 weeks prior to randomization, must meet the following criteria: ANC must be greater than or equal to 1200/mm3; Platelet count must be greater than or equal to 100,000/mm3; and Hemoglobin must be greater than or equal to 10 g/dL.
- The following criteria for evidence of adequate hepatic function must be met based on the results of the most recent postoperative tests performed within 6 weeks prior to randomization: total bilirubin must be less than or equal to upper limit of normal (ULN) for the lab unless the patient has a bilirubin elevation > ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin; and alkaline phosphatase must be less than or equal to 2.5 x ULN for the lab; and AST must be less than or equal to 1.5 x ULN for the lab. Alkaline phosphatase and AST may not both be > the ULN.
- Patients with AST or alkaline phosphatase > ULN are eligible for inclusion in the study if liver imaging (CT, MRI, PET scan, or PET-CT scan performed within 3 months prior to randomization) does not demonstrate metastatic disease and the requirements for evidence of adequate hepatic function are met.
- Patients with alkaline phosphatase that is > ULN but less than or equal to 2.5 x ULN are eligible for inclusion in the study if a bone scan,PET scan, or PET-CT scan (performed within 3 months prior to randomization) does not demonstrate metastatic disease.
- The following criteria for renal function must be met based on the results of the most recent postoperative tests performed within 6 weeks prior to randomization: Serum creatinine must be less than or equal to ULN for the lab. Measured or calculated creatinine clearance must be > 60 mL/min.
- A urine sample must be tested for protein by determination of the urine protein/creatinine (UPC) ratio or by urine dipstick. UPC ratio must be less than 1.0. Urine dipstick must indicate 0-1+ protein. If dipstick reading is greater than or equal to 2+, determine the UPC ratio, which must be less than 1.0, or collect a 24-hour urine specimen, which must demonstrate < 1.0 g of protein per 24 hours.
- LVEF assessment must be performed within 3 months prior to randomization. The LVEF must be greater than or equal to 55% regardless of the cardiac imaging facility's lower limit of normal (LLN).
- The ECG (performed within 3 months prior to randomization) must not have demonstrated any of the following conditions: ventricular arrhythmias except for benign premature ventricular contractions; supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; and conduction abnormality requiring a pacemaker.
Exclusion Criteria:
- Inflammatory breast cancer.
- Definitive clinical or radiologic evidence of metastatic disease. (Chest imaging [mandatory for all patients] and other imaging [if required] must have been performed within 3 months prior to randomization.)
- Synchronous or previous contralateral invasive breast cancer (Patients with synchronous or previous contralateral DCIS or LCIS are eligible).
- History of ipsilateral invasive breast cancer regardless of treatment or ipsilateral DCIS treated with excision and RT. (Patients with history of ipsilateral LCIS are eligible.)
- History of non-breast malignancies within the 5 years prior to study entry, except for the following: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinomas of the skin.
- Previous therapy with anthracyclines, taxanes, carboplatin, trastuzumab, or bevacizumab for any malignancy.
- RT, chemotherapy, and/or targeted therapy, administered for the currently diagnosed breast cancer prior to randomization.
- Continued therapy with any hormonal agent such as raloxifene or tamoxifen (or other SERM) or an aromatase inhibitor. (Patients are eligible if these medications are discontinued prior to randomization.)
- Any sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy, etc. Patients are eligible if these medications are discontinued prior to randomization.
- Cardiac disease (history of and/or active disease) that would preclude the use of the drugs included in the treatment regimens. This includes but is not confined to: Active cardiac disease - angina pectoris that requires the use of anti-anginal medication; ventricular arrhythmias except for benign premature ventricular contractions; supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; conduction abnormality requiring a pacemaker; valvular disease with documented compromise in cardiac function; and symptomatic pericarditis. History of cardiac disease - myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LV function; history of documented CHF; and documented cardiomyopathy.
- Uncontrolled hypertension defined as systolic blood pressure (BP) > 150 mmHg or diastolic BP > 90 mmHg, with or without anti-hypertensive medication. (BP must be assessed within 28 days prior to randomization.) Patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria.
- History of hypertensive crisis or hypertensive encephalopathy.
- History of TIA or CVA.
- History of any arterial thrombotic event within 12 months before randomization.
- Symptomatic peripheral vascular disease.
- Intrinsic lung disease resulting in dyspnea.
- Unstable diabetes mellitus.
- Active infection or chronic infection requiring chronic suppressive antibiotics.
- Any significant bleeding within 6 months before randomization, exclusive of menorrhagia in premenopausal women.
- Non-healing wound, skin ulcers, or incompletely healed bone fracture.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to planned start of study therapy.
- Anticipation of need for major surgical procedures during study therapy and for at least 3 months following completion of bevacizumab.
- Gastroduodenal ulcer(s) documented by endoscopy to be active within 6 months before randomization.
- History of GI perforation, abdominal fistulae, or intra-abdominal abscess.
- Known bleeding diathesis or coagulopathy.
- Requirement for therapeutic doses of coumadin or equivalent.
- Sensory/motor neuropathy greater than or equal to grade 2, as defined by the NCI CTCAE v3.0.
- Conditions that would prohibit administration of corticosteroids.
- Chronic daily treatment with corticosteroids (dose of > 10 mg/day methylprednisolone equivalent) (excluding inhaled steroids).
- History of hypersensitivity reaction to drugs formulated with polysorbate 80.
- Pregnancy or lactation at the time of study entry. (Note: Pregnancy testing must be performed within 14 days prior to randomization according to institutional standards for women of child-bearing potential.)
- Other non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up.
- Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.
- Use of any investigational product within 4 weeks prior to enrollment in the study.
Sites / Locations
- University of Alabama at Birmingham
- Clearview Cancer Institute-Decatur
- Clearview Cancer Institute
- Clearview Cancer Institute- Huntsville
- Northern Arizona Hematology & Onclogy Associates
- Northern Arizona Hematology & Oncology Associates
- Central Hematology/Oncology Medical Group, Inc.
- Comprehensive Blood and Cancer Center
- Kaiser Permanente-Baldwin Park
- Kaiser Permanente-Bellflower
- Providence Saint Joseph Medical Center
- Hematology-Encinitas
- Scripps Clinic Encinitas
- Kaiser Permanente-Fontana
- St. Jude Heritage Healthcare
- Breastlink Medical Group, Inc
- Pacific Shores Medical Group
- Kaiser Permanente-Irvine
- Hematology-La Jolla
- Sabina R. Wallach, MD., AMC
- Scripps Cancer Center-San Diego
- Antelope Valley Cancer Center
- Kaiser Permanente-Sunset
- Kaiser Permanente-West Los Angeles
- Kaiser Permanente-Oakland
- North County Oncology Medical Clinic, Inc.
- Kaiser Permanente-Panorama City
- Kaiser Permanente-Orange County
- Wilshire Oncology Medical Group
- Cancer Care Associates Medical Group, Inc.
- Kaiser Permanente-Riverside
- Kaiser Permanente-Roseville
- Sutter Roseville Medical Center
- Kaiser Permanente-Sacramento
- Sutter Medical Center
- Sutter Medical Group
- Peter T. Reissman, MD, Inc
- William Stanton, MD, Inc
- Kaiser Permanente-San Diego
- Sharp Rees-Stealy
- Scripps Clinic-Rancho Bernardo
- Kaiser Permanente-San Francisco
- Kaiser Permanente-Hayward
- Sansum Clinic
- Santa Barbara Hematology Oncology Medical Group
- Kaiser Permanente-Santa Clara
- Central Coast Medical Oncology Corporation
- Kaiser Permanente-South San Francisco
- Stanford University Medical Center
- UCLA/Santa Clarita Valley Cancer Center
- Kaiser Permanente-Vallejo
- San Diego Pacific Oncology & Hematology-Vista
- Kaiser Permanente-Walnut Creek
- Kaiser Permanente-Woodland Hills
- University of Colorado Cancer Center
- Penrose Cancer Center
- Kaiser Permanente-Franklin
- Cypress Hematology/Oncology
- Rocky Mountain Cancer Center - Midtown
- CCOP-Colorado Cancer Research Prog. Inc.(Administrative Only)
- Shaw Regional Cancer Center
- North Colorado Medical Center
- Kaiser Permanente Rock Creek
- McKee Medical Center
- Exempla Lutheran Medical Center
- Oncology Associates P.C.-Avon
- Medical Specialists of SWIM
- Bridgeport Hospital
- Medical Specialists of Fairfield
- Oncology Associates of Bridgeport-Fairfield
- Hartford Hospital
- Connecticut Multi Specialty Group-Hartford
- Oncology Associates P.C.-Hartford
- Medical Oncology and Hematology, P.C.
- Eastern Connecticut Hematology & Oncology Associates
- Black Rock Medical Group
- Oncology Associates of Bridgeport-Trumbull
- Medical Oncology & Hematology, P.C.
- Connecticut Multi Specialty Group-Wethersfield
- Oncology Associates P.C.-Willimantic
- CCOP, Christiana Care Health Services Inc.
- Washington Cancer Institute
- Sibley Memorial Hospital
- Washington Oncology-Hematology Center, PC-Washington
- Lynn Cancer Institute
- Florida Cancer Specialists-Bonita Springs
- Florida Cancer Specialists-Bradenton
- Florida Cancer Specialists, Brandon
- Florida Cancer Specialists-Cape Coral Parkway
- Florida Cancer Specialists-Cape Coral Del Prado
- Florida Cancer Specialists
- Florida Cancer Specialists-Englewood
- Florida Cancer Specialists-Fort Myers Broadway
- Florida Cancer Specialists-Fort Myers Summerlin
- Robert R. Carroll, MD, PA
- Integrated Community Oncology Network
- Lakeland Regional Cancer Center
- Florida Cancer Specialists-Naples Goodlette
- Florida Cancer Specialists-NAPA Ridge
- Integrated Community Oncology Network
- Florida Hospital Cancer Institute
- Florida Cancer Specialists, Cornerstone
- Florida Cancer Specialists-Port Charlotte
- Florida Cancer Specialists-Park Place
- Florida Cancer Specialist-Cattleman
- Florida Cancer Specialists-Downtown
- Florida Cancer Specialists
- Florida Cancer Specialists
- Florida Cancer Specialists-Venice Island
- Florida Cancer Specialists-Venice
- Palm Beach Cancer Institute
- Phoebe Putney Memorial Hospital
- Northeast Georgia Cancer Care, LLC
- Grady Healthsystem
- Emory University
- Augusta Oncology Associates
- Northwest Georgia Oncology Centers PC
- Northwest Georgia Oncology Centers PC
- Northwest Georgia Oncology Centers PC
- Suburban Hematology-Oncology Associates
- Central Georgia Cancer Care
- Georgia Cancer Specialists
- Georgia Cancer Specialists
- Suburban Hematology Oncology Associates PC
- Oncare Hawaii, Inc-POB2
- Straub Clinic and Hospital
- University of Hawaii
- Oncare Hawaii, Inc-KMP
- Kootenai Cancer Center
- Mountain States Tumor Institute
- Mountain States Tumor Institute
- Cancer Care & Hematology Specialists of Chicagoland
- MBCCOP, John H. Stroger, JR., Hospital of Cook County-Chicago
- Rush University Medical Center
- Crossroads Cancer Center
- Cancer Care Specialists-Central Illinois
- Decatur Memorial Hospital
- Edward Hospital
- Edward Cancer Center Plainfield
- Cancer Care and Hematology Specialists of Chicagoland
- Yorkville Family Practice
- Cancer Care of Southern Indiana
- Corydon Hospital Medical Plaza
- Elkhart Clinic
- Michiana Hematology-Oncology, P.C. (Elkhart)
- Waverly Hematology Oncology
- Clark Medical Building
- Howard Regional Health System
- Michiana Hematology-Oncology, P.C. (LaPorte)
- Cancer Care Center
- Michiana Hematology-Oncology PC
- Oncology, P.C. Plymouth
- South Bend Clinic
- Michiana Hematology-Oncology, P.C. (Main Office)
- Northern Indiana Cancer Research Consortium
- Michiana Hematology-Oncology, P.C. Cedar St.
- Providence Medical Group
- Hematology and Medical Oncology Consultants-Bettendorf
- Hematology and Medical Oncology Consultants-Davenport
- University of Iowa
- Lawrence Memorial Hospital
- University of Kentucky Medical Center
- NortonHealthcare Pavillion
- Norton Medical Plaza II
- Norton Medical Plaza West
- Old Brownsboro Crossing
- Baton Rouge General Medical Center
- Eastern Maine Medical Center
- Mercy Medical Center
- Greater Baltimore Medical Center
- Franklin Square Hospital Center
- Harry & Jeannette Weinberg Cancer Institute
- Hematology-Oncology Associates
- Carolyn Hendricks, MD
- Suburban Hospital
- The Office of Frederik Smith
- Washington Oncology-Hematology Center, PC-Chevy Chase
- Associates in Oncology/Hematology
- Peninsula Regional Oncology & Hematology
- Peninsula Regional Medical Center
- Holy Cross Hospital
- Oncology Care Associates
- Berkshire Hematology Oncology, P.C.-North Adams
- Berkshire Hematology Oncology, P.C.
- Bixby Medical Center
- CCOP, St. Joseph Mercy Hospital
- Battle Creek Health System
- Bay Regional Medical Center
- Dr. Cook and Abramson - Bay City
- St. Joseph Mercy Woodland Health Center
- Josephone Ford Cancer Center
- Henry Ford Medical Center-Fairlane
- Henry Ford Hospital
- UP Hematology/Oncology Assoc.-Doctor's Park Family Physicians
- CCOP Hurley Medical Center
- Genesys Hurley
- Sing and Arora
- Genesys Regional Medical Center
- Grand Rapids Clinical Oncology Program
- Spectrum Health Hospitals
- St. Mary's Health Services
- CCOP, St. John Hospital and Medical Center
- Portage Internal Medical Associates
- UP Hematology/Oncology Associates
- UP Hematology/Oncology Associates-Gogebic Range
- West Michigan Cancer Center
- Hematology/Oncology Associates of OH and MI, PC
- CCOP, Sparrow Health System
- Michigan State University - Breslin Cancer Center
- Hematology Oncology-Lapeer
- Lapeer Regional Hospital
- Keewanaw Memorial Hospital
- St. Mary Mercy Hospital - Livonia
- Marquette General Hospital
- Upper Peninsula Hematology/Oncology Associates
- Community Cancer Care Specialists-Mt. Clemens
- Mount Clemens Regional Medical Center
- Hackley Hospital
- Michiana Hematology-Oncology PC
- CCOP, William Beaumont Hospital
- CCOP, St. Mary's Medical Center
- Lakeside Cancer Specialists, PLLC
- Michiana Hematology-Oncology, PC Lakeland
- Chippewa Medical Associates
- Osteopathic Medical Oncology Hematology
- Munson Medical Center
- CCOP, St. John Macomb Hospital
- Henry Ford Medical Center-West Bloomfield
- Metro Health Hospital
- Minnesota Oncology Hematology-Burnsville
- Park Nicollet Clinic
- Hubert H. Humphrey Cancer Center - Coon Rapids
- Minnesota Oncology Hematology-Edina
- Fairview Southdale Medical Oncology Clinic
- Hubert H. Humphrey Cancer Center - Fridley
- Minnesota Oncology Hematology PA - Maplewood
- Minnesota Oncology Hematology-Minneapolis
- Hubert H. Humphrey Cancer Center-Robbinsdale
- Park Nicollet Health Services
- Minnesota Hematology Oncology-St. Paul
- Minnesota Oncology Hematology-Waconia
- Minnesota Oncology Hematology
- University of Tennessee Cancer Institute
- University of Missouri-Ellis Fischel
- Freeman Cancer Institute
- St. John's Regional Health Center-Joplin
- Saint Luke's Hospital
- CCOP, Kansas City (Administrative Only)
- St. John's Regional Health Center
- Cox Health Systems
- Hematology Oncology Centers of the Northern Rockies
- Comprehensive Cancer Centers of Nevada (Siena)
- University Medical Center of Southern Nevada
- Cancer and Blood Specialists- Shadow Lane
- Cancer Consultants
- Nevada Cancer Institute
- Renown Regional Medical Center
- Alpine Hematology-Oncology
- Summit Medical Group
- Drs. Forte, Schleider, Attas and Condemi, PA
- Cancer Institute of New Jersey at Hamilton
- Monmouth Medical Center
- Morristown Memorial Hospital
- Cancer Institute of New Jersey
- University of Medicine and Dentistry of New Jersey
- Newark Beth Israel Medical Center
- Sparta Cancer Treatment Center
- Overlook Hospital
- New York Oncology Hematology PC-Albany
- NY Oncology Hematology PC at Albany Medical Center
- Amsterdam Community Cancer Program
- Interlakes Oncology & Hematology, P.C.
- Hematology Oncology Assaociates of CNY, CCOP
- NY Oncology Hematology PC-Hudson Carvell Cancer Tx Prog.
- NY Oncology Hematology PC- Latham- Capital District Oncology Hematology
- Beth Israel Medical Center
- St. Luke's-Roosevelt Hospital Center
- Riverview Cancer Care Medical Association
- Hematology Oncology Associates of CNY, CCOP
- University Hospital and Medical Center - SUNY
- University Hospital and Medical Center-SUNY
- Hematology Oncology Assoc. of CNY, CCOP (Comm. General Hospital Satellite Office)
- Troy Cancer Treatment Program
- Cancer Care of Western North Carolina
- CCOP, Mission Hospitals, Inc.
- Cancer Center of NC at Asheville
- Carolinas Hematology-Oncology Associates - Tyron St
- Carolinas Medical Center - Blumenthal Cancer Center
- CCOP Presbyterian Hospital
- Mecklenburg Medical Group - Morehead Medical Dr
- Mecklenburg Medical Group - Cameron Valley Pkwy
- Carolinas Hematology Oncology Associates - Harris Blvd.
- Carolinas Hematology-Oncology - John J. Delaney
- CCOP, Wayne Memorial Hospital
- Moses Cone Regional Cancer Center
- Northwestern Carolina Oncology & Hematology, PA
- Carolina BioOncology Institute
- Akron City Hospital
- Akron General Medical Center
- Alliance Cancer Center
- Aultman Hospital
- Tri County Hematology/Oncology
- Kenwood Office
- Oncology/Hematology Care Clinical Trials LLC
- North Treatment Center - Blue Ash Medical Center
- Oncology/Hematology Care Clinical Trials LLC, Cincinnati, OH Blue Ash Med. Cntr. (Administrative Only)
- Oncology/Hematology Care Clinical Trials LLC
- Case Western Reserve/University Hospitals-Ireland Cancer Cntr.
- Dayton Physicians-LLC-Hematology & Medical Oncology Division
- Healthplex
- Dayton Physicians, LLC - Greenville
- Hamilton Office
- Dayton Clinical Oncology Program-Kettering
- Marian A. Llenado Lee, MD, Inc.
- Northwest Ohio Oncology Center
- UHHS - Chagrin Highlands
- UHHS Green Road-Ireland Cancer Center
- Flower Memorial Hospital
- Bayview Oncology Associates
- Toledo Clinic
- UHHS Westlake-Ireland Cancer Center
- Northwest Cancer Specialists-Portland
- Providence Portland Medical Center
- Adventist Medical Center
- Northwest Cancer Specialists-Adventist Office
- CCOP, Columbia River Oncology
- Providence Oncology and Hematology Care Clinic
- Providence St. Vincent Medical Center
- Lehigh Valley Hospital
- Geisinger Clinic
- Hematology Oncology Associates of NE PA
- Ephrata Cancer Center at Ephrata Community Hospital
- UPMC Cancer Centers Arnold Palmer Pavilion-Mountainview
- UPMC Cancer Centers Arnold Palmer-Oakbrook
- UPMC Cancer Centers-Indiana
- UPMC Cancer Centers-John P. Murtha Cancer Center
- UPMC Cancer Centers - McKeesport Hospital
- Riddle Memorial Hospital
- UPMC Cancer Centers Arnold Palmer-Mt. Pleasant
- Kimmel Cancer Center at Jefferson
- Cancer Center at Center One
- Albert Einstein Healthcare Network
- Allegheny General Hospital/Allegheny-Singer Research Institute
- NSABP Foundation, Inc
- University of Pittsburgh
- UPMC Cancer Centers - UPMC St. Margaret
- Hillman Cancer Center
- UPMC Cancer Centers - UPMC Passavant
- Mercy Hospital
- Scranton Hematology Oncology
- Hematology and Oncology Associates
- Mount Nittany Medical Center
- UPMC Cancer Centers-Uniontown
- UPMC Cancer Centers - Wexford
- York Hospital
- Thompson Oncology Group-Blount
- Thompson Cancer Survival Center-Dowell Springs
- Thompson Cancer Survival Center
- Thompson Oncology Group-West
- The West Clinic
- Texas Oncology- Sammons CC
- The Center for Cancer and Blood Disorders
- Baylor College of Medicine
- Ben Taub General Hospital
- Covenant Health System dba Joe Arrington Cancer Research & Treatment Center
- North Texas Regional Cancer Center
- Intermountain Medical Center
- McKay-Dee Hospital
- Utah Valley Regional Medical Center
- Dixie Medical Center
- LDS Hospital
- VCU Massey Cancer Center at Stony Point
- MBCCOP, Virginia Commonwealth University
- Overlake Internal Medicine
- Rockwood Cancer Treatment Center - Sinto Ave
- Rockwood Cancer Treatment Center
- Southwest Washington Hospital
- Northwest Cancer Specialists-136th Ave
- Northwest Cancer Specialists-134th St.
- West Virginia University Hospitals Inc.
- Oncology Alliance-Burlington
- Oncology Alliance-Franklin
- Oncology Alliance
- Aurora BayCare Medical Center
- Oncology Alliance-Kenosha South
- Oncology Alliance-Kenosha North
- CCOP, Marshfield Clinic
- Oncology Alliance-Menomonee Falls
- Oncology Alliance-Mequon
- Oncology Alliance-South
- Oncology Alliance-Racine
- Oncology Alliance-Waukeska
- Marshfield Clinic Weston Center
- Hospital Universitario Austral
- Breast Clinica de la mama
- Centro Oncologico Rosario (COR)
- Hospital Britanico de Buenos Aires
- CEMIC
- Macarthur Cancer Center
- St. George Hospital
- Cancer Therapy Center
- North Shore Private Hospital
- Royal North Shore Hospital
- Southern Medical Day Care
- Royal Brisbane & Women's Hospital
- Mater Adult Hospital
- Ashford Cancer Center
- Flinders Medical Centre
- Frankston Hospital
- The Alfred Hospital
- Mount Medical Center
- Berdat Family Comprehensive Cancer Centre
- Krankenhaus Barmherzige Brueder Graz, Medizinische Abteilung
- Universitatsfrauenklinik Graz
- Medizinische Universitat Graz - Onkologie
- AI University Hospital Innsbruck
- Bezirkskrankenhaus Kufstein, Innere Medizin
- Landeskrankenhaus Leoben, Abteilung fur Haemato-Onkologie
- Krankenhaus Barmherzige Schwestern Linz, Kooperative Studiengruppe, Chirurgie
- AI Universitätsklinikum der PMU Landeskliniken
- AKH Vienna
- Medizinische Universitaet Wien-Allgemeines Krankenhaus, Onkologie
- Krankenhaus Hietzing, Gynaekologische Abteilung
- Landeskrankenhaus Voecklabruck, 2. Medizinische Abteilung
- Klinikum Wels-Grieskirchen, Kooperative Gruppe Wels/4. Medizinische Abteilung
- AZ Klina
- C. H. Notre-Dame and Reine Fabiola
- Clinique St Pierre
- Medical Institute St. Augustinus
- Clinical Centre University of Sarajevo
- Centro Goiano de oncologia
- Lifecenter Sistema de Saude S/A
- Instituto Nacional de Cancer
- Clinica Oncologistas Associados
- Assoiacao hospital de caridade de ijui
- Hospital Das Clinicas de Porto Alegre-HCPA
- Irmandade da Santa Casa de Misericoria de Porto Alegre Nucleo de Novos Tratamentos
- Clinica de Oncologia de Porto Alegre
- Fundacao Dr. Amaral Carvalho
- Instituto de Oncologia Clinica de Piracicaba
- Centro de Oncologia e Hematologia da Faculdade de Medicina do ABC
- Instituto do Cancer de Sao Paulo
- Conjunto Hospitalar de Sorocaba
- District Oncology Dispensary Plovdiv
- MHAT "Tsaritsa Yoanna-ISUL" EOOD
- Tom Baker Cancer Centre
- Cross Cancer Institute, Dept of Medicine
- Lion's Gate Hospital
- Dr. H. Bliss Murphy Cancer Centre
- William Osler Health Center
- Credit Valley Hospital
- Southlake Regional Health Centre
- Ottawa Hospital Regional Cancer Centre
- St. Michaels Hospital
- Humber River Regional Hospital
- Windsor Regional Cancer Centre
- Hopital Charles LeMoyne
- Hopital Maisonneuve Rosemont
- Royal Victoria Hospital
- Montreal General Hospital
- Jewish General Hospital
- Hospital du Sacre-Coeur
- University of Montreal Hospital Group
- Centre Hospitalier Affilie Universitaire De Quebec, Hospital du St-Sacrement
- Hospital Regional Rancagua
- Chinese Academy of Medical Science
- The Pla 307 Hospital
- Chinese PLA General Hospital
- Jilin Cancer Hospital
- West China Hospital, Sichuan University
- Fuzhou General Hospital of Nanjing Military Area
- Sun Yat-sen University Hospital
- 1st Affiliated Hospital of Zhejiang University
- Zhejiang Tumor Hospital
- Tianjin Cancer Hospital
- University Hospital Zagreb
- FN Na Bulovce
- National Cancer Institute
- Tartu University Hospital Clinic of Hematology and Oncology
- CHU D'Amiens
- CH-Service Hemato-Oncologie
- Clinique Bordeaux Nord Aquitaine
- CHU Morvan
- Hopital Pasteur
- Ch intercommunal de creteil
- Centre Leonard de Vinci
- Institut Daniel Hollard
- CHD les Oudairies
- Clinique Francois Chenieux
- CHU Dupuytren
- Hopital St. Joseph
- Centre Regional de Lutte contre le Cancer (CRLC) Val d'Aurelle
- Centre Catherine de Sienne
- Clinique Hartmann
- Hopital St. Antoine
- CHU Hotel Dieu
- Clinique Saint Hilaire
- Pole de cancerologie prive
- CLCC Paul Strauss
- Institution Claudius Regaud
- Polyclinique du Parc
- Klinikum St. Marien Amberg
- Hochwaldkrankenhaus
- Klinikverbund Suedwest - Sindelfingen-Böeblingen Clinical Centre
- Klinikum Chemnitz
- Universitaetsklinikum Dresden
- Luisenkrankenhaus
- Universitaetsfrauenklinik
- Zentrum fur Frauenheilkunde und Geburtshilfe
- Medizinisches Versorgungszentrum Osthessen
- Kreiskrankenhaus Hameln
- Klinikum Stadt Hanau
- Klinikum Hannover Nordstadt
- Universitat Frauenklinik Jena
- Onkologische schwerpunktpraxis
- Klinikum Lippe Lemgo
- Asklepios Kliniken Lich GmbH
- Universitaetsklinikum Mainz
- St. Vincenz u. Elisabeth Hospital
- RotKreuzKlinikum München GmbH
- Universitaetsklinikum Munster
- Ev Krankenhaus Bethesda
- Praxis und Tagesklinik fuer Onkologie und
- Klinikum Rosenheim
- Klinikum Schaumburg
- Johanniter Krankenhaus
- Robert-Bosch-Krankenhaus
- Fachärzte fürlnnere Medizin, Hämatologie
- P.G. Hospital of Thessaloniki "Papageorgiou"
- Prince of Wales Hospital
- Queen Elizabeth Hospital
- Semmelweis Egyetem Clinic of Radiology
- DEOEC Onkologiai Tanszek
- Petz Aladar Megyei Oktato
- Kaposi Mor oktato korhaz Onkologiai tanszek
- Cork University Hospital
- St. Vincent's University Hospital
- Beaumont Hospital
- St. James's Hospital
- Adelaide and Meath National Childrens Hospital
- Institute for Cancer Research
- Mater Private Hospital
- University College Hospital Galway
- Midwestern Regional Hospital
- Sligo General Hospital
- The Lady Davis Carmel Medical Center/Lynn
- Meir Medical Center
- Kaplan Medical Center
- Sourasky (Ichilov) Medical Center
- Ziv Medical Center
- Assaf Harofeh Medical Center
- Humanitas Centro Catanese
- (Azienda u.s.I. chieti) - Policinico Ospedaliero
- Ospedale vito fazzi
- Ospedale di Mirano
- IRCCS - Instituto Nazionale per lo Studio e la Cura
- Fondazione Salvatore Maugeri
- Ospedale S. Filippo Neri
- Regina Elena Cancer Institute
- Ospedale casa sollievo della sofferenza
- Universita-istituto Clinica Medica
- Asl n. 5 -Ospedale s. Vincenzo
- Seoul National University Bundang Hospital
- Seoul National University Hospital
- Severance Hospital
- Samsung Medical Center
- Asan Medical Center
- P. Stradina Clinical University Hospital
- Opcion Oncologia
- Hospital Nacional Carlos Alberto Seguin
- Hospital Nacional Edgardo Rebagliati Martins
- Cebu Doctors University Hospital
- Regional Oncology Center
- Centrum Onkologii Instytut im. M.
- ZOZ MSWiA z Warminsko-Mazurskim Centrum
- Olsztynski Osrodek Onkologiczny "Kopernik"
- Samodzielny Publiczny Zaklad Opieki
- Breast Cancer Clinic
- HUC
- IPO Francisco Gentil-Porto
- County Hospital Alba-Iulia
- Institute of Oncology "AI.Trestioreanu"
- Institutul Oncologic "Prof. Dr. I. Chiricuta" Cluj-Napoca
- State Medical Institution "Republican Clinical Oncology Dispensary Ministry of Health of Republic Tatarstan"
- State Institution "Russian Oncological Research Center n.a. N.N. Blokhin of RAMS"
- Federal State Institution "Research Institute of Oncology n.a. N.N. Petrov Rosmedtechnologiy"
- Saint-Petersburg State Medical Institution "City Clinical Oncology Dispensary"
- Clinical Hospital Center Bezanijska Kosa
- Clinic of Oncology, Clinical Center nis
- University Clinical Centre
- Department of Oncotherapy National Hospital
- Hopelands Cancer Centre
- Johannesburg Hospital
- Hospital Universitario Insular de Gran Canaria
- Fundacion Hospitalaria de Alcorcon
- Hospital General de Alicante
- Hospital Perpetuo Socorro
- Hospital Germans Trias l Pujol
- Hospital Comarcal de Barbastro
- Hospital Del Mar
- Hospital Santa Crue l San Pau
- Hospital Clinic i Provincial
- Consorci Sanitari de Terrassa
- Althaia Xarxa Assistencial de Manresa
- Hospital Espiritu Santo
- Hospital De San Pedro de Alcantara
- Hospital Gral. De Elche
- Hospital de Cabueñes, Oncologia Médica
- Instituto Catalan Oncologia de Girona
- Complejo Hospitalario de Jaen
- Complejo Hospitalario Universitario A Coruna
- Centro Oncologico de Galicia
- Hospital Universitario de Canarias
- Hospital Xera Calde
- Hospital Universitario Gregorio Maranon
- Hospital Ruber International
- Fundacion Jimenez Diaz
- Hospital Universitario San Carlos
- Centro Integral de Oncologia "Clara Campal"
- Hospital Clinico Virgen de la Victoria
- Hospital Univesitario Carlos Haya
- Hospital Santa Maria Nai Dr. Cabaleiro
- Complejo Hospitalario de Pontevedra
- Hospital del Parc Tauli
- Hospital Universitario de Salamanca
- Instituto Oncologico de Guipuzcoa
- Hospital Universitario Virgen del Rocio
- Hospital Torrevieja Salud, UTE
- Hospital Clinico Universitario de Valencia
- Hospital Clinico Universitario Lozano Blesa
- Hospital U. Miguel Servet
- Sahlgrenska University Hospital
- Karolinska University Hospital
- Changhua Christian Hospital
- Kaohsiung Medical University Chung
- National Cheng Kung University
- Sun Yat-Sen Cancer Center
- Taipei Veterans General Hospital
- Chang Gung Memorial Hospital
- Chulalongkorn Hospital
- National Cancer Institute
- Songklanagarind Hospital
- Royal Bournemouth Hospital
- Bristol Hematology - Oncology Centre
- Ipswich Hospital
- Christie Hospital NHS Trust
- Nottingham City Hospital
- Peterborough District Hospital
- Sunrise Cancer Centre
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Active Comparator
Experimental
Active Comparator
Experimental
1A: TCH-H
1B: TCHB-HB
2A: TH-FEC-H
2B: THB-FEC-HB
Docetaxel (T), Carboplatin (C), and Trastuzumab (H) followed by Trastuzumab (H)
Docetaxel (T), Carboplatin (C), Trastuzumab (H), Bevacizumab (B) followed by Trastuzumab (T) and Bevacizumab (B)
Docetaxel (T) and Trastuzumab (H) followed by 5-fluorouracil (F), Epirubicin (E), and Cyclophosphamide (C) followed by Trastuzumab (H)
Docetaxel (T), Trastuzumab (H), and Bevacizumab (B) followed by 5-Fluorouracil (F), Epirubicin (E), and Cyclophosphamide (C) followed by Trastuzumab (H) and Bevacizumab (B)