Doxorubicin Hydrochloride, Cyclophosphamide, and Paclitaxel With or Without Bevacizumab in Treating Patients With Lymph Node-Positive or High-Risk, Lymph Node-Negative Breast Cancer
Breast Adenocarcinoma

About this trial
This is an interventional treatment trial for Breast Adenocarcinoma
Eligibility Criteria
Inclusion Criteria:
Patients must have histologically confirmed adenocarcinoma of the breast at significant risk of distant recurrence based on at least one of the following criteria:
For axillary lymph node positive disease:
- Involvement of at least one sentinel or axillary lymph node on routine histologic examination; patients with negative sentinel nodes and negative axillary nodes or involvement only demonstrated by immunohistochemistry are not eligible unless they meet one of the other eligibility criteria below
- NOTE: consider intramammary nodes as equivalent to axillary nodes for the purposes of eligibility and stratification
For axillary lymph node negative disease:
- Estrogen receptor (ER) negative tumor >= 1 cm
- ER+ tumor >= 5 cm regardless of recurrence score
- ER+ tumor >= 1 cm but < 5 cm with a recurrence score >= 11 (patients enrolled in the TAILORx trial are eligible)
- NOTE: axillary dissection is strongly encouraged in patients with lymph node involvement identified on sentinel node biopsy
Patients must have completed definitive breast surgery including total mastectomy and axillary dissection (modified radical mastectomy), total mastectomy and sentinel node biopsy, breast conservation surgery and axillary dissection or breast conservation surgery and sentinel node biopsy
- NOTE: breast conservation surgery includes lumpectomy, partial mastectomy, and excisional biopsy
- Margins of breast conservation surgery or mastectomy must be histologically free of invasive breast cancer and ductal carcinoma in situ (DCIS); patients with resection margins positive for lobular carcinoma in situ (LCIS) are eligible
- Time from last surgery for breast cancer (breast conservation surgery, mastectomy, sentinel node biopsy, axillary dissection or re-excision of breast conservation surgery margins) to planned treatment start date must be > 28 days and =< 84 days
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Within =< 8 weeks prior to randomization: Absolute neutrophil count >= 1,000/mm^3
- Within =< 8 weeks prior to randomization: Platelet count >= 100,000/mm^3
- Within =< 8 weeks prior to randomization: Total bilirubin =< 1.5 mg/dL
- Within =< 8 weeks prior to randomization: Aspartate aminotransferase (AST) =< 2 times upper limit of normal(ULN)
- Within =< 8 weeks prior to randomization: Serum creatinine =< 1.5 mg/dL
- Within =< 8 weeks prior to randomization: Urine protein:creatinine ratio < 1.0 or 24-hour protein
- Within =< 8 weeks prior to randomization: Partial thromboplastin time (PTT) =< 1.5 times ULN
- Within =< 8 weeks prior to randomization: Left ventricle ejection fraction (LVEF) >= institutional limits of normal by multigated acquisition scan (MUGA) or echocardiogram (ECHO)
Patients who have undergone breast conservation surgery must receive radiation; prior to randomization, the investigator must specify the planned radiation technique:
- Whole breast radiation (WBRT) after chemotherapy
- Accelerated partial breast radiation (APBI) after chemotherapy
- Accelerated partial breast radiation (APBI) prior to chemotherapy
- NOTE: if APBI was completed prior to study entry, day 1 of protocol therapy must be at least 4 weeks after the completion of APBI
- Post-mastectomy radiation therapy (RT) is required for all patients with a primary tumor of >= 5 cm or involvement of 4 or more lymph nodes; post-mastectomy RT may be administered at the investigator's discretion for all other mastectomy patients
- Patients with human epidermal growth factor receptor (HER)2 + (3+ by immunohistochemistry [IHC] or fluorescent in situ hybridization [FISH] ratio >= 2) breast cancer are not eligible
- Patients with synchronous bilateral breast cancer (diagnosed within one month) are eligible if the higher tumor, node, metastasis (TNM) stage tumor meets the eligibility criteria for this trial
- Patients must not have clinical evidence of inflammatory disease or fixed axillary nodes at diagnosis
Patients must not have received prior cytotoxic chemotherapy or hormonal therapy for this breast cancer; prior treatment with an anthracycline, anthracenedione or taxane for any condition is not allowed
- NOTE: prior use of tamoxifen for chemoprevention is allowed but must be discontinued at study entry; similarly, prior raloxifene use is allowed but must be discontinued at study entry
Patients must not have had any major surgical procedure within 28 days of planned treatment start date
- NOTE: non-operative biopsy or placement of a vascular access device is not considered a major surgery
- Patients may not have had placement of a vascular access device within 24 hours of planned day 1 of treatment
Patients must not have clinically significant cardiovascular or cerebrovascular disease, including:
Any history of
- Cerebrovascular disease including transient ischemic attack (TIA), stroke or subarachnoid hemorrhage
- Ischemic bowel
Within the last 12 months
- Myocardial infarction
- Unstable angina
- New York Heart Association (NYHA) class II or greater congestive heart failure
- Grade II or greater peripheral vascular disease
- Uncontrolled hypertension defined as systolic blood pressure (SBP) > 160 or diastolic blood pressure (DBP) > 90
- Uncontrolled or clinically significant arrhythmia
- NOTE: blood pressure must be obtained within =< 8 weeks prior to randomization
- NOTE: patients with controlled atrial fibrillation are eligible
Patients who require full-dose anticoagulation may enroll provided they meet the following criteria:
- The patient must have an in-range international normalized ratio (INR) (usually between 2 and 3) on a stable dose of warfarin or be on stable dose of low molecular weight (LMW) heparin
- The patient must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. varices)
- NOTE: prophylactic use of anticoagulants to maintain patency of a vascular access device is permitted
- Patients must not have a bleeding diathesis, hereditary or acquired bleeding disorder or coagulopathy
- Patients must not have a non-healing wound or fracture; patients with an abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization are not eligible
- Patients must not have hypersensitivity to paclitaxel or drugs using the vehicle Cremophor, Chinese hamster ovary cell products or other recombinant human antibodies
- Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood or urine test within 7 days prior to randomization to rule out pregnancy
- Women of childbearing potential and sexually active males must use an accepted and effective method of contraception
Sites / Locations
- Northeast Alabama Regional Medical Center
- University of Alabama at Birmingham Cancer Center
- Providence Hospital
- Alaska Regional Hospital
- Providence Alaska Medical Center
- Virginia G Piper Cancer Care-Del Camino
- Mayo Clinic in Arizona
- Mercy Hospital Fort Smith
- University of Arkansas for Medical Sciences
- Kaiser Permanente-Deer Valley Medical Center
- PCR Oncology
- Alta Bates Summit Medical Center-Herrick Campus
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
- Mills-Peninsula Medical Center
- East Bay Radiation Oncology Center
- Eden Hospital Medical Center
- Valley Medical Oncology Consultants-Castro Valley
- Bay Area Breast Surgeons Inc
- Kaiser Permanente-Fremont
- Valley Medical Oncology Consultants-Fremont
- Washington Hospital
- California Cancer Associates for Research and Excellence (cCare)
- Glendale Memorial Hospital and Health Center
- Marin Cancer Care Inc
- Marin General Hospital
- UC San Diego Moores Cancer Center
- USC / Norris Comprehensive Cancer Center
- Contra Costa Regional Medical Center
- Fremont - Rideout Cancer Center
- Community Hospital of Monterey Peninsula
- El Camino Hospital
- Palo Alto Medical Foundation-Camino Division
- Sutter Cancer Research Consortium
- Highland General Hospital
- Alta Bates Summit Medical Center - Summit Campus
- Bay Area Tumor Institute
- Hematology and Oncology Associates-Oakland
- Tom K Lee Inc
- Kaiser Permanente-Oakland
- Desert Regional Medical Center
- Palo Alto Medical Foundation Health Care
- Stanford Cancer Institute Palo Alto
- Valley Care Health System - Pleasanton
- Valley Medical Oncology Consultants
- Pomona Valley Hospital Medical Center
- Eisenhower Medical Center
- Kaiser Permanente-Redwood City
- Kaiser Permanente-Richmond
- Kaiser Permanente-Roseville
- University of California Davis Comprehensive Cancer Center
- Kaiser Permanente-South Sacramento
- Kaiser Permanente - Sacramento
- Saint Helena Hospital
- Salinas Valley Memorial
- UC San Diego Medical Center - Hillcrest
- Kaiser Permanente-San Diego Mission
- Sharp Memorial Hospital
- Zuckerberg San Francisco General Hospital
- California Pacific Medical Center-Pacific Campus
- Kaiser Permanente-San Francisco
- UCSF Medical Center-Mount Zion
- Kaiser Permanente-Santa Teresa-San Jose
- Kaiser Permanente San Leandro
- Doctors Medical Center- JC Robinson Regional Cancer Center
- Kaiser Permanente-San Rafael
- Kaiser Permanente Medical Center - Santa Clara
- Kaiser Permanente-Santa Rosa
- Kaiser Permanente-South San Francisco
- Kaiser Permanente-Stockton
- Gene Upshaw Memorial Tahoe Forest Cancer Center
- Kaiser Permanente-Vallejo
- Sutter Solano Medical Center/Cancer Center
- Kaiser Permanente-Walnut Creek
- The Medical Center of Aurora
- Boulder Community Hospital
- Penrose-Saint Francis Healthcare
- UCHealth Memorial Hospital Central
- Kaiser Permanente-Franklin
- Porter Adventist Hospital
- Presbyterian - Saint Lukes Medical Center - Health One
- SCL Health Saint Joseph Hospital
- Rose Medical Center
- Western States Cancer Research NCORP
- Swedish Medical Center
- Poudre Valley Hospital
- Saint Mary's Hospital and Regional Medical Center
- North Colorado Medical Center
- Kaiser Permanente-Rock Creek
- Saint Anthony Hospital
- Sky Ridge Medical Center
- Longmont United Hospital
- McKee Medical Center
- Saint Mary Corwin Medical Center
- North Suburban Medical Center
- SCL Health Lutheran Medical Center
- Danbury Hospital
- Smilow Cancer Hospital Care Center at Saint Francis
- Middlesex Hospital
- The Hospital of Central Connecticut
- Norwalk Hospital
- Stamford Hospital/Bennett Cancer Center
- Smilow Cancer Hospital-Torrington Care Center
- Bayhealth Hospital Kent Campus
- Beebe Medical Center
- Christiana Care Health System-Christiana Hospital
- MedStar Georgetown University Hospital
- MedStar Washington Hospital Center
- Sibley Memorial Hospital
- George Washington University Medical Center
- Howard University Hospital
- Lynn Regional Cancer Center - West
- Boca Raton Comprehensive Cancer Center
- Boca Raton Regional Hospital
- Halifax Health Medical Center-Centers for Oncology
- Broward Health North
- Holy Cross Hospital
- Broward Health Medical Center
- Florida Cancer Specialists-Gainesville Cancer Center
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital
- Mayo Clinic in Florida
- Jupiter Medical Center
- Lakeland Regional Health Hollis Cancer Center
- The Watson Clinic
- Cancer Centers of Central Florida PA
- Mount Sinai Medical Center
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- AdventHealth Orlando
- Cleveland Clinic-Weston
- University Cancer and Blood Center LLC
- Grady Health System
- Emory University Hospital Midtown
- Piedmont Hospital
- Emory University Hospital/Winship Cancer Institute
- Atlanta Regional CCOP
- Emory Saint Joseph's Hospital
- Northside Hospital
- Augusta University Medical Center
- WellStar Cobb Hospital
- John B Amos Cancer Center
- Dekalb Medical Center
- Eisenhower Army Medical Center
- Northeast Georgia Medical Center-Gainesville
- Northside Hospital - Gwinnett
- Medical Center of Central Georgia
- Wellstar Kennestone Hospital
- Southern Regional Medical Center
- Harbin Clinic Medical Oncology and Clinical Research
- Memorial Health University Medical Center
- Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
- Pali Momi Medical Center
- Hawaii Cancer Care Inc - Waterfront Plaza
- Queen's Medical Center
- Straub Clinic and Hospital
- University of Hawaii Cancer Center
- Queen's Cancer Center - Kuakini
- The Cancer Center of Hawaii-Liliha
- Kapiolani Medical Center for Women and Children
- Maui Memorial Medical Center
- Pacific Cancer Institute of Maui
- Saint Alphonsus Cancer Care Center-Boise
- Saint Luke's Cancer Institute - Boise
- Kootenai Clinic Cancer Services - Post Falls
- Saint Anthony's Health
- Rush - Copley Medical Center
- MacNeal Hospital and Cancer Center
- Saint Joseph Medical Center
- Illinois CancerCare-Bloomington
- Graham Hospital Association
- Illinois CancerCare-Canton
- Illinois CancerCare-Carthage
- Memorial Hospital
- Mount Sinai Hospital Medical Center
- Hematology and Oncology Associates
- Northwestern University
- John H Stroger Jr Hospital of Cook County
- Rush University Medical Center
- University of Illinois
- Swedish Covenant Hospital
- Presence Resurrection Medical Center
- University of Chicago Comprehensive Cancer Center
- Weiss Memorial Hospital
- UChicago Medicine Comprehensive Cancer Center - Saint Joseph Hospital
- Decatur Memorial Hospital
- Heartland Cancer Research NCORP
- Advocate Sherman Hospital
- Ascension Alexian Brothers - Elk Grove Village
- Elmhurst Memorial Hospital
- Eureka Hospital
- Illinois CancerCare-Eureka
- NorthShore University HealthSystem-Evanston Hospital
- Saint Francis Hospital
- Galesburg Cottage Hospital
- Illinois CancerCare-Cottage
- Illinois CancerCare-Galesburg
- Ingalls Memorial Hospital
- Illinois CancerCare-Havana
- Mason District Hospital
- Hematology Oncology Associates of Illinois-Highland Park
- Hinsdale Hematology Oncology Associates Incorporated
- Hopedale Medical Complex - Hospital
- Midwest Center for Hematology Oncology
- Duly Health and Care Joliet
- Presence Saint Mary's Hospital
- Illinois CancerCare-Kewanee Clinic
- AMITA Health Adventist Medical Center
- AMG Libertyville - Oncology
- Illinois CancerCare-Macomb
- Mcdonough District Hospital
- Loyola University Medical Center
- Garneau, Stewart C MD (UIA Investigator)
- Porubcin, Michael MD (UIA Investigator)
- Sharis, Christine M MD (UIA Investigator)
- Spector, David MD (UIA Investigator)
- Stoffel, Thomas J MD (UIA Investigator)
- Trinity Medical Center
- Holy Family Medical Center
- Illinois CancerCare-Monmouth
- Good Samaritan Regional Health Center
- DuPage Medical Group-Ogden
- Illinois Cancer Specialists-Niles
- Bromenn Regional Medical Center
- Carle Cancer Institute Normal
- Illinois CancerCare-Community Cancer Center
- Mid-Illinois Hematology Oncology Associates Limited
- Advocate Christ Medical Center
- Illinois CancerCare-Ottawa Clinic
- Ottawa Regional Hospital and Healthcare Center
- Advocate Lutheran General Hospital
- Illinois CancerCare-Pekin
- OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
- Pekin Hospital
- Proctor Hospital
- Illinois CancerCare-Peoria
- Methodist Medical Center of Illinois
- OSF Saint Francis Medical Center
- Illinois CancerCare-Peru
- Illinois Valley Hospital
- Illinois CancerCare-Princeton
- Perry Memorial Hospital
- West Suburban Medical Center
- Swedish American Hospital
- OSF Saint Anthony Medical Center
- Edward H Kaplan MD and Associates
- Hematology Oncology Associates of Illinois - Skokie
- Illinois CancerCare-Spring Valley
- Saint Margaret's Hospital
- Memorial Medical Center
- Carle Cancer Center
- Northwestern Medicine Cancer Center Warrenville
- Northwestern Medicine Central DuPage Hospital
- Ascension Saint Vincent Anderson
- Franciscan Saint Francis Health-Beech Grove
- IU Health Bloomington
- Elkhart Clinic
- Michiana Hematology Oncology PC-Elkhart
- Elkhart General Hospital
- Fort Wayne Medical Oncology and Hematology Inc-Parkview
- Goshen Center for Cancer Care
- Indiana University/Melvin and Bren Simon Cancer Center
- Sidney and Lois Eskenazi Hospital
- Franciscan Health Indianapolis
- Ascension Saint Vincent Indianapolis Hospital
- Community Howard Regional Health
- IU Health La Porte Hospital
- IU Health Arnett Cancer Care
- Horizon Oncology Research LLC
- Premier Oncology Hematology Associates
- Franciscan Saint Anthony Health-Michigan City
- Michiana Hematology Oncology PC-Mishawaka
- Saint Joseph Regional Medical Center-Mishawaka
- IU Health Ball Memorial Hospital
- The Community Hospital
- Michiana Hematology Oncology PC-Plymouth
- Reid Health
- Memorial Hospital of South Bend
- Michiana Hematology Oncology PC-South Bend
- South Bend Clinic
- Northern Indiana Cancer Research Consortium
- Michiana Hematology Oncology PC-Westville
- McFarland Clinic - Ames
- Constantinou, Costas L MD (UIA Investigator)
- University of Iowa Healthcare Cancer Services Quad Cities
- Physicians' Clinic of Iowa PC
- Saint Luke's Hospital
- Mercy Hospital
- Oncology Associates at Mercy Medical Center
- Medical Oncology and Hematology Associates-West Des Moines
- Heartland Oncology and Hematology LLP
- Genesis Medical Center - East Campus
- Genesis Cancer Care Institute
- Mercy Capitol
- Iowa Methodist Medical Center
- Iowa-Wide Oncology Research Coalition NCORP
- Medical Oncology and Hematology Associates-Des Moines
- Mercy Medical Center - Des Moines
- Mission Cancer and Blood - Laurel
- Iowa Lutheran Hospital
- Mercy Medical Center - North Iowa
- Ottumwa Regional Health Center
- Siouxland Regional Cancer Center
- Mercy Medical Center-Sioux City
- Saint Luke's Regional Medical Center
- Cedar Valley Medical Specialists
- MercyOne Waterloo Cancer Center
- Cancer Center of Kansas - Chanute
- Cancer Center of Kansas - Dodge City
- Cancer Center of Kansas - El Dorado
- Cancer Center of Kansas - Fort Scott
- Cancer Center of Kansas-Independence
- University of Kansas Cancer Center
- Cancer Center of Kansas-Kingman
- Lawrence Memorial Hospital
- Southwest Medical Center
- Cancer Center of Kansas-Liberal
- Cancer Center of Kansas - Newton
- Olathe Cancer Center
- Cancer Center of Kansas - Parsons
- Cancer Center of Kansas - Pratt
- Cancer Center of Kansas - Salina
- Salina Regional Health Center
- Cotton O'Neil Cancer Center / Stormont Vail Health
- University of Kansas Health System Saint Francis Campus
- Cancer Center of Kansas - Wellington
- Associates In Womens Health
- Cancer Center of Kansas-Wichita Medical Arts Tower
- Ascension Via Christi Hospitals Wichita
- Cancer Center of Kansas - Wichita
- Wichita NCI Community Oncology Research Program
- Cancer Center of Kansas - Winfield
- King's Daughter's Medical Center
- The James Graham Brown Cancer Center at University of Louisville
- Doctors Carrol, Sheth, Raghavan
- Owensboro Health Mitchell Memorial Cancer Center
- Baton Rouge General Medical Center
- Mary Bird Perkins Cancer Center
- Ochsner Health Center-Summa
- Ochsner Health Center-Covington
- DeSoto Regional Health System
- Ochsner LSU Health Monroe Medical Center
- Louisiana State University Health Science Center
- University Medical Center New Orleans
- Ochsner Medical Center Jefferson
- LSU Health Sciences Center at Shreveport
- Highland Clinic
- Harold Alfond Center for Cancer Care
- Eastern Maine Medical Center
- Central Maine Medical Center
- Maine Center for Cancer Medicine-Scarborough
- Maine General Medical Center-Thayer
- York Hospital
- Anne Arundel Medical Center
- University of Maryland/Greenebaum Cancer Center
- Greater Baltimore Medical Center
- MedStar Union Memorial Hospital
- MedStar Franklin Square Medical Center/Weinberg Cancer Institute
- MedStar Good Samaritan Hospital
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Suburban Hospital
- University of Maryland Shore Medical Center at Easton
- Christiana Care - Union Hospital
- Frederick Memorial Hospital
- Associates in Oncology Hematology PC -Kensington
- Maryland Oncology Hematology PA-Aquilino Cancer Center
- Holy Cross Hospital
- Sturdy Memorial Hospital
- Tufts Medical Center
- Massachusetts General Hospital Cancer Center
- Brigham and Women's Hospital
- Boston Medical Center
- Beth Israel Deaconess Medical Center
- Dana-Farber Cancer Institute
- Steward Saint Elizabeth's Medical Center
- Lahey Hospital and Medical Center
- MetroWest Medical Center-Framingham Union Hospital
- Addison Gilbert Hospital
- Cape Cod Hospital
- Lowell General Hospital
- Norwood Hospital
- Berkshire Medical Center - Cancer Center
- Baystate Medical Center
- Michigan Cancer Research Consortium NCORP
- Saint Joseph Mercy Hospital
- Bronson Battle Creek
- Spectrum Health Big Rapids Hospital
- Beaumont Hospital - Dearborn
- Wayne State University/Karmanos Cancer Institute
- Ascension Saint John Hospital
- Green Bay Oncology - Escanaba
- Hurley Medical Center
- Genesys Regional Medical Center-West Flint Campus
- Cancer Research Consortium of West Michigan NCORP
- Spectrum Health at Butterworth Campus
- Trinity Health Grand Rapids Hospital
- Holland Community Hospital
- Green Bay Oncology - Iron Mountain
- Allegiance Health
- Bronson Methodist Hospital
- West Michigan Cancer Center
- Borgess Medical Center
- Sparrow Hospital
- Trinity Health Saint Mary Mercy Livonia Hospital
- MyMichigan Medical Center Midland
- McLaren Cancer Institute-Macomb
- Mercy Health Partners-Hackley Campus
- Trinity Health Muskegon Hospital
- Lakeland Hospital Niles
- McLaren Cancer Institute-Northern Michigan
- Saint Joseph Mercy Oakland
- Lake Huron Medical Center
- William Beaumont Hospital-Royal Oak
- Ascension Saint Mary's Hospital
- Lakeland Medical Center Saint Joseph
- Marie Yeager Cancer Center
- Oncology Care Associates PLLC
- Ascension Providence Hospitals - Southfield
- Munson Medical Center
- Saint John Macomb-Oakland Hospital
- University of Michigan Health - West
- Medini, Eitan MD (UIA Investigator)
- Sanford Joe Lueken Cancer Center
- Fairview Ridges Hospital
- Mercy Hospital
- Essentia Health Cancer Center
- Essentia Health Saint Mary's Medical Center
- Miller-Dwan Hospital
- Saint Luke's Hospital of Duluth
- Fairview Southdale Hospital
- Etzell, Paul S MD (UIA Investigator)
- Lake Region Healthcare Corporation-Cancer Care
- Swenson, Wade II, MD (UIA Investigator)
- Unity Hospital
- Hutchinson Area Health Care
- Meeker County Memorial Hospital
- Mayo Clinic Health Systems-Mankato
- Minnesota Oncology Hematology PA-Maplewood
- Saint John's Hospital - Healtheast
- Abbott-Northwestern Hospital
- Virginia Piper Cancer Institute
- Hennepin County Medical Center
- University of Minnesota/Masonic Cancer Center
- North Memorial Medical Health Center
- Mayo Clinic in Rochester
- Coborn Cancer Center at Saint Cloud Hospital
- Saint Cloud Hospital
- Metro Minnesota Community Oncology Research Consortium
- Park Nicollet Clinic - Saint Louis Park
- Regions Hospital
- Saint Joseph's Hospital - Healtheast
- United Hospital
- Saint Francis Regional Medical Center
- Ridgeview Medical Center
- Rice Memorial Hospital
- Minnesota Oncology Hematology PA-Woodbury
- Woodwinds Health Campus
- Keesler Medical Center
- Central Care Cancer Center - Bolivar
- Southeast Missouri Hospital
- Saint Francis Medical Center
- Saint Luke's Hospital
- Veterans Administration
- MU Health - University Hospital/Ellis Fischel Cancer Center
- Freeman Health System
- Mercy Hospital Joplin
- Missouri Cancer Care PC - Saint Charles
- Saint Louis Cancer and Breast Institute-South City
- Washington University School of Medicine
- Missouri Baptist Medical Center
- Center for Cancer Care and Research
- Comprehensive Cancer Care PC
- Mercy Hospital Saint Louis
- Saint Louis-Cape Girardeau CCOP
- Cancer Research for the Ozarks NCORP
- Mercy Hospital Springfield
- CoxHealth South Hospital
- Billings Clinic Cancer Center
- Northern Rockies Radiation Oncology Center
- Saint Vincent Healthcare
- Montana Cancer Consortium NCORP
- Saint Vincent Frontier Cancer Center
- Bozeman Deaconess Hospital
- Saint James Community Hospital and Cancer Treatment Center
- Benefis Healthcare- Sletten Cancer Institute
- Berdeaux, Donald MD (UIA Investigator)
- Great Falls Clinic
- Northern Montana Hospital
- Saint Peter's Community Hospital
- Glacier Oncology PLLC
- Kalispell Medical Oncology
- Kalispell Regional Medical Center
- Montana Cancer Specialists
- Saint Patrick Hospital - Community Hospital
- Community Medical Hospital
- Guardian Oncology and Center for Wellness
- CHI Health Good Samaritan
- Nebraska Cancer Research Center
- Cancer Alliance of Nebraska
- Missouri Valley Cancer Consortium
- Nebraska Methodist Hospital
- Alegent Health Immanuel Medical Center
- Alegent Health Bergan Mercy Medical Center
- Creighton University Medical Center
- University Medical Center of Southern Nevada
- Nevada Cancer Research Foundation NCORP
- New Hampshire Oncology Hematology PA-Concord
- Wentworth-Douglass Hospital
- Exeter Hospital
- Cheshire Medical Center-Dartmouth-Hitchcock Keene
- LRGHealthcare-Lakes Region General Hospital
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
- Norris Cotton Cancer Center-Manchester
- Solinsky Center for Cancer Care
- Foundation Medical Partners
- Ocean University Medical Center
- Cooper Hospital University Medical Center
- Englewood Hospital and Medical Center
- Hunterdon Medical Center
- Hackensack University Medical Center
- The Cancer Institute of New Jersey Hamilton
- Saint Barnabas Medical Center
- Morristown Medical Center
- Virtua Memorial
- Jersey Shore Medical Center
- Saint Peter's University Hospital
- Rutgers Cancer Institute of New Jersey
- Rutgers New Jersey Medical School
- Saint Michael's Medical Center
- Newark Beth Israel Medical Center
- Saint Joseph's Regional Medical Center
- Capital Health Medical Center-Hopewell
- AtlantiCare Regional Medical Center -Main Campus
- Riverview Medical Center/Booker Cancer Center
- Valley Hospital
- Sparta Cancer Treatment Center
- Overlook Hospital
- Inspira Medical Center Vineland
- Virtua Voorhees
- Lovelace Medical Center-Saint Joseph Square
- University of New Mexico Cancer Center
- Hematology Oncology Associates
- Presbyterian Kaseman Hospital
- Memorial Medical Center - Las Cruces
- San Juan Regional Medical Center
- New York Oncology Hematology PC - Albany
- New York Oncology Hematology PC - Albany Medical Center
- New York Oncology Hematology PC - Amsterdam
- Lincoln Medical and Mental Health Center
- Montefiore Medical Center-Weiler Hospital
- Montefiore Medical Center-Wakefield Campus
- Montefiore Medical Center - Moses Campus
- Maimonides Medical Center
- Coney Island Hospital
- Roswell Park Cancer Institute
- New York Oncology Hematology PC - Clifton Park
- Finger Lakes Hematology and Oncology
- Mary Imogene Bassett Hospital
- Hematology Oncology Associates of Central New York-East Syracuse
- Elmhurst Hospital Center
- Arnot Ogden Medical Center/Falck Cancer Center
- New York Oncology Hematology PC-Hudson
- Queens Hospital Center
- Garnet Health Medical Center
- Mount Kisco Medical Group at Northern Westchester Hospital
- Northern Westchester Hospital
- Mount Sinai Union Square
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- Mount Sinai West
- Mount Sinai Hospital
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
- Memorial Sloan Kettering Cancer Center
- NYP/Weill Cornell Medical Center
- Champlain Valley Physicians Hospital Medical Center
- Hudson Valley Hematology Oncology Associates
- The Dyson Center for Cancer Care
- Vassar Brothers Medical Center
- Highland Hospital
- Interlakes Foundation Inc-Rochester
- University of Rochester
- Staten Island University Hospital
- Richmond University Medical Center
- Stony Brook University Medical Center
- State University of New York Upstate Medical University
- New York Oncology Hematology PC - Troy
- Faxton-Saint Luke's Healthcare
- Randolph Hospital
- Mission Hospital
- Hope Women's Cancer Centers-Asheville
- Cone Health Cancer Center at Alamance Regional
- Waverly Hematology Oncology
- UNC Lineberger Comprehensive Cancer Center
- Novant Health Presbyterian Medical Center
- Atrium Health Cabarrus/LCI-Concord
- Southeastern Medical Oncology Center-Goldsboro
- Wayne Memorial Hospital
- Cone Health Cancer Center
- East Carolina University
- Margaret R Pardee Memorial Hospital
- Vidant Oncology-Kinston
- FirstHealth of the Carolinas-Moore Regional Hospital
- UNC Rex Healthcare
- Annie Penn Memorial Hospital
- Rutherford Hospital
- Marion L Shepard Cancer Center at Vidant Beaufort Hospital
- Southeast Clinical Oncology Research Consortium NCORP
- Wake Forest University Health Sciences
- Mid Dakota Clinic
- Saint Alexius Medical Center
- Sanford Bismarck Medical Center
- Essentia Health Cancer Center-South University Clinic
- Sanford Broadway Medical Center
- Sanford Clinic North-Fargo
- Altru Cancer Center
- Trinity Cancer Care Center
- Cleveland Clinic Akron General
- Mary Rutan Hospital
- Cleveland Clinic Mercy Hospital
- Aultman Health Foundation
- Adena Regional Medical Center
- The Christ Hospital
- Case Western Reserve University
- MetroHealth Medical Center
- Ohio State University Comprehensive Cancer Center
- Riverside Methodist Hospital
- Columbus NCI Community Oncology Research Program
- Grant Medical Center
- Mount Carmel Health Center West
- Doctors Hospital
- Grandview Hospital
- Good Samaritan Hospital - Dayton
- Miami Valley Hospital
- Miami Valley Hospital North
- Dayton Veterans Affairs Medical Center
- Dayton NCI Community Oncology Research Program
- Grady Memorial Hospital
- Blanchard Valley Hospital
- Atrium Medical Center-Middletown Regional Hospital
- Wayne Hospital
- Kettering Medical Center
- Fairfield Medical Center
- Saint Rita's Medical Center
- Marietta Memorial Hospital
- Knox Community Hospital
- Licking Memorial Hospital
- Springfield Regional Medical Center
- Upper Valley Medical Center
- Saint Ann's Hospital
- Clinton Memorial Hospital
- Wright-Patterson Medical Center
- Greene Memorial Hospital
- Genesis Healthcare System Cancer Care Center
- Cancer Centers of Southwest Oklahoma Research
- Cancer Care Associates-Norman
- University of Oklahoma Health Sciences Center
- Cancer Care Associates
- Mercy Hospital Oklahoma City
- Mercy Physicians of Oklahoma-Lakeside
- Natalie Warren Bryant Cancer Center at Saint Francis
- Bay Area Hospital
- Three Rivers Community Hospital
- Legacy Mount Hood Medical Center
- Asante Health System
- Providence Medford Medical Center
- Rogue Valley Medical Center
- Providence Milwaukie Hospital
- Legacy Good Samaritan Hospital and Medical Center
- Providence Portland Medical Center
- Adventist Medical Center
- Providence Saint Vincent Medical Center
- Compass Oncology Rose Quarter
- Kaiser Permanente Northwest
- Legacy Emanuel Hospital and Health Center
- Oregon Health and Science University
- Salem Hospital
- Legacy Meridian Park Hospital
- Jefferson Abington Hospital
- Lehigh Valley Hospital-Cedar Crest
- Saint Luke's University Hospital-Bethlehem Campus
- Bryn Mawr Hospital
- Geisinger Medical Center
- Mercy Fitzgerald Hospital
- Doylestown Hospital
- Delaware County Memorial Hospital
- Oncology Hematology Associates of Northern Pennsylvania
- Pocono Medical Center
- Easton Hospital
- Ephrata Cancer Center
- UPMC Hillman Cancer Center Erie
- Saint Vincent Hospital
- UPMC Pinnacle Cancer Center/Community Osteopathic Campus
- Geisinger Medical Center-Cancer Center Hazleton
- Penn State Milton S Hershey Medical Center
- Armstrong Center for Medicine and Health
- Lancaster General Hospital
- Saint Mary Medical and Regional Cancer Center
- Central PA Hematology-Medical Oncology Associates PC
- Lewistown Hospital
- Holy Redeemer Hospital and Medical Center
- Riddle Memorial Hospital
- Paoli Memorial Hospital
- University of Pennsylvania/Abramson Cancer Center
- Pennsylvania Hospital
- Thomas Jefferson University Hospital
- Fox Chase Cancer Center
- Einstein Medical Center Philadelphia
- Phoenixville Hospital
- Allegheny General Hospital
- UPMC-Magee Womens Hospital
- University of Pittsburgh Cancer Institute (UPCI)
- Pottstown Hospital
- Penn State Health Saint Joseph Medical Center
- Guthrie Medical Group PC-Robert Packer Hospital
- Mercy Hospital
- Hematology and Oncology Associates of North East Pennsylvania
- Scranton Hematology Oncology
- Grand View Hospital
- Geisinger Medical Group
- Mount Nittany Medical Center
- Chester County Hospital
- Jennersville Regional Hospital
- Reading Hospital
- Geisinger Wyoming Valley/Henry Cancer Center
- Geisinger South Wilkes-Barre
- UPMC Susquehanna
- Lankenau Medical Center
- Main Line Health NCORP
- WellSpan Health-York Hospital
- Rhode Island Hospital
- Women and Infants Hospital
- Miriam Hospital
- Kent Hospital
- AnMed Health Hospital
- Roper Hospital
- Medical University of South Carolina
- McLeod Regional Medical Center
- Spartanburg Medical Center
- Avera Cancer Institute-Aberdeen
- Rapid City Regional Hospital
- Sanford Cancer Center Oncology Clinic
- Avera Cancer Institute
- Medical X-Ray Center
- Avera McKennan Hospital and University Health Center
- Sanford USD Medical Center - Sioux Falls
- Wellmont Medical Associates Oncology and Hematology-Bristol
- Erlanger Medical Center
- Vanderbilt-Ingram Cancer Center Cool Springs
- Wellmont Holston Valley Hospital and Medical Center
- Thompson Cancer Survival Center
- University of Tennessee - Knoxville
- University of Tennessee Health Science Center
- Nashville Oncology Associates PC
- Vanderbilt Breast Center at One Hundred Oaks
- Meharry Medical College
- Vanderbilt University/Ingram Cancer Center
- Medical City Dallas Hospital
- Parkland Memorial Hospital
- Clements University Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- Brooke Army Medical Center
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
- Wilford Hall Medical Center
- Scott and White Memorial Hospital
- Huntsman Cancer Institute/University of Utah
- Southwestern Vermont Medical Center
- Central Vermont Medical Center/National Life Cancer Treatment
- University of Vermont and State Agricultural College
- University of Virginia Cancer Center
- Inova Schar Cancer Institute
- Peninsula Cancer Institute-Gloucester
- Centra Lynchburg Hematology-Oncology Clinic Inc
- Peninsula Cancer Institute-Newport News
- Southwest VA Regional Cancer Center
- Peninsula Cancer Institute-Williamsburg
- MultiCare Auburn Medical Center
- Providence Regional Cancer System-Centralia
- Saint Francis Hospital
- Saint Clare Hospital
- Providence - Saint Peter Hospital
- MultiCare Good Samaritan Hospital
- MultiCare Allenmore Hospital
- MultiCare Tacoma General Hospital
- Northwest NCI Community Oncology Research Program
- Saint Joseph Medical Center
- PeaceHealth Southwest Medical Center
- Legacy Salmon Creek Hospital
- Providence Saint Mary Regional Cancer Center
- North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
- West Virginia University Charleston Division
- Edwards Comprehensive Cancer Center
- Saint Mary's Medical Center
- West Virginia University Healthcare
- Camden Clark Medical Center
- Princeton Community Hospital
- Langlade Hospital and Cancer Center
- ThedaCare Regional Cancer Center
- Aurora Cancer Care-Southern Lakes VLCC
- Marshfield Clinic-Chippewa Center
- HSHS Sacred Heart Hospital
- Marshfield Clinic Cancer Center at Sacred Heart
- Saint Agnes Hospital/Agnesian Cancer Center
- Aurora Cancer Care-Franklin
- Aurora Health Care Germantown Health Center
- Aurora Cancer Care-Glendale
- Green Bay Oncology at Saint Vincent Hospital
- Saint Vincent Hospital Cancer Center Green Bay
- Green Bay Oncology Limited at Saint Mary's Hospital
- Saint Vincent Hospital Cancer Center at Saint Mary's
- Aurora BayCare Medical Center
- Mercyhealth Hospital and Cancer Center - Janesville
- UW Cancer Center Johnson Creek
- Aurora Cancer Care-Kenosha South
- Gundersen Lutheran Medical Center
- Mayo Clinic Health System-Franciscan Healthcare
- Dean Hematology and Oncology Clinic
- University of Wisconsin Carbone Cancer Center
- Holy Family Memorial Hospital
- Aurora Bay Area Medical Group-Marinette
- Bay Area Medical Center
- Marshfield Medical Center-Marshfield
- Marshfield Medical Center
- Ascension Columbia Saint Mary's Hospital Ozaukee
- Ascension Columbia Saint Mary's Hospital - Milwaukee
- Aurora Saint Luke's Medical Center
- Aurora Sinai Medical Center
- Marshfield Clinic-Minocqua Center
- ProHealth Oconomowoc Memorial Hospital
- Saint Vincent Hospital Cancer Center at Oconto Falls
- Vince Lombardi Cancer Clinic - Oshkosh
- Ascension All Saints Hospital
- Aurora Cancer Care-Racine
- Ascension Saint Mary's Hospital
- Marshfield Medical Center-Rice Lake
- Vince Lombardi Cancer Clinic-Sheboygan
- Ascension Saint Michael's Hospital
- Green Bay Oncology - Sturgeon Bay
- Aurora Medical Center in Summit
- Vince Lombardi Cancer Clinic-Two Rivers
- Aurora Cancer Care-Waukesha
- ProHealth Waukesha Memorial Hospital
- Aspirus Regional Cancer Center
- Marshfield Clinic-Wausau Center
- Aurora Cancer Care-Milwaukee West
- Aurora West Allis Medical Center
- Diagnostic and Treatment Center
- Marshfield Medical Center - Weston
- Aspirus Cancer Care - Wisconsin Rapids
- Marshfield Clinic - Wisconsin Rapids Center
- Rocky Mountain Oncology
- Welch Cancer Center
- Instituto Nacional de Enfermedades Neoplasicas
- University Of Pretoria
Arms of the Study
Arm 1
Arm 2
Arm 3
Active Comparator
Experimental
Experimental
Arm I (chemotherapy, placebo)
Arm II (chemotherapy, bevacizumab)
Arm III (chemotherapy, bevacizumab monotherapy)
Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV over 20-30 minutes, and placebo IV over 30-90 minutes on day 1. Treatment repeats every 2 or 3 weeks for 4 courses. Beginning 3 weeks later, patients then receive paclitaxel IV over 1 hour on days 1, 8, and 15 and placebo IV over 30-90 minutes on day 1. Treatment with paclitaxel and placebo repeats every 3 weeks for 4 courses.
Patients receive doxorubicin hydrochloride and cyclophosphamide as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 2 or 3 weeks for 4 courses. Beginning 3 weeks later, patients then receive paclitaxel as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment with paclitaxel and bevacizumab repeats every 3 weeks for 4 courses.
Patients receive doxorubicin hydrochloride and cyclophosphamide as in arm I and bevacizumab as in arm II. Treatment repeats every 2 or 3 weeks for 4 courses. Beginning 3 weeks later, patients then receive paclitaxel as in arm I and bevacizumab as in arm II. Treatment with paclitaxel and bevacizumab repeats every 3 weeks for 4 courses. Beginning 2 months later, patients then receive bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab alone repeats every 3 weeks for 10 courses.