AzTrials
AzTrials

Breast AdenocarcinomaPhase 3NCT00433511

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

A Phase 3 study testing Bevacizumab, Cyclophosphamide and Doxorubicin Hydrochloride in people with Breast Adenocarcinoma, run by National Cancer Institute (NCI) at 842 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

This randomized phase III trial studies doxorubicin hydrochloride, cyclophosphamide, and paclitaxel to see how well they work with or without bevacizumab in treating patients with cancer that has spread to the lymph nodes (lymph node-positive) or cancer that has not spread to the lymph nodes but is at high risk for… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Adenocarcinoma
What is being tested?
Bevacizumab, Cyclophosphamide and Doxorubicin Hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
4,994 participants
Where
842 sitesin 3 countries
Study dates
2 Nov 2007to 20 Feb 2027
Phase
Phase 3

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 58Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

842 sites in 3 countries.

302 sites in 3 countries

United States300 sites

  • Pali Momi Medical Center

    ‘Aiea, Hawaii, 96701

  • Avera Cancer Institute-Aberdeen

    Aberdeen, South Dakota, 57401

  • Jefferson Abington Hospital

    Abington, Pennsylvania, 19001

  • Cleveland Clinic Akron General

    Akron, Ohio, 44307

  • New York Oncology Hematology PC - Albany

    Albany, New York, 12206

  • New York Oncology Hematology PC - Albany Medical Center

    Albany, New York, 12208

  • Lovelace Medical Center-Saint Joseph Square

    Albuquerque, New Mexico, 87102

  • Hematology Oncology Associates

    Albuquerque, New Mexico, 87106

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • Presbyterian Kaseman Hospital

    Albuquerque, New Mexico, 87110

  • Medini, Eitan MD (UIA Investigator)

    Alexandria, Minnesota, 56308

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • OSF Saint Anthony's Health Center

    Alton, Illinois, 62002

  • McFarland Clinic - Ames

    Ames, Iowa, 50010

  • New York Oncology Hematology PC - Amsterdam

    Amsterdam, New York, 12010

  • Alaska Regional Hospital

    Anchorage, Alaska, 99508

  • Providence Alaska Medical Center

    Anchorage, Alaska, 99508

  • Ascension Saint Vincent Anderson

    Anderson, Indiana, 46016

  • AnMed Health Hospital

    Anderson, South Carolina, 29621

  • Michigan Cancer Research Consortium NCORP

    Ann Arbor, Michigan, 48106

  • Trinity Health Saint Joseph Mercy Hospital Ann Arbor

    Ann Arbor, Michigan, 48106

  • Luminis Health Anne Arundel Medical Center

    Annapolis, Maryland, 21401

  • Northeast Alabama Regional Medical Center

    Anniston, Alabama, 36202

  • Aspirus Cancer Care-Antigo-Volm Cancer Center

    Antigo, Wisconsin, 54409

  • Kaiser Permanente-Deer Valley Medical Center

    Antioch, California, 94531

  • ThedaCare Regional Cancer Center

    Appleton, Wisconsin, 54911

  • PCR Oncology

    Arroyo Grande, California, 93420

  • Randolph Hospital

    Asheboro, North Carolina, 27203

  • Mission Hospital

    Asheville, North Carolina, 28801

  • Hope Women's Cancer Centers-Asheville

    Asheville, North Carolina, 28816

  • King's Daughter's Medical Center

    Ashland, Kentucky, 41101

  • University Cancer and Blood Center LLC

    Athens, Georgia, 30607

  • Grady Health System

    Atlanta, Georgia, 30303

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Piedmont Hospital

    Atlanta, Georgia, 30309

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Atlanta Regional CCOP

    Atlanta, Georgia, 30342

  • Emory Saint Joseph's Hospital

    Atlanta, Georgia, 30342

  • Northside Hospital

    Atlanta, Georgia, 30342

  • Sturdy Memorial Hospital

    Attleboro, Massachusetts, 02703

  • MultiCare Auburn Medical Center

    Auburn, Washington, 98001

  • Augusta University Medical Center

    Augusta, Georgia, 30912

  • Harold Alfond Center for Cancer Care

    Augusta, Maine, 04330

  • The Medical Center of Aurora

    Aurora, Colorado, 80012

  • Rush-Copley Medical Center

    Aurora, Illinois, 60504

  • WellStar Cobb Hospital

    Austell, Georgia, 30106

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Greater Baltimore Medical Center

    Baltimore, Maryland, 21204

  • MedStar Union Memorial Hospital

    Baltimore, Maryland, 21218

  • MedStar Franklin Square Medical Center/Weinberg Cancer Institute

    Baltimore, Maryland, 21237

  • MedStar Good Samaritan Hospital

    Baltimore, Maryland, 21239

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Baton Rouge General Medical Center

    Baton Rouge, Louisiana, 70806

  • Mary Bird Perkins Cancer Center

    Baton Rouge, Louisiana, 70809

  • Ochsner Health Center-Summa

    Baton Rouge, Louisiana, 70809

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

  • Franciscan Saint Francis Health-Beech Grove

    Beech Grove, Indiana, 46107

  • Mary Rutan Hospital

    Bellefontaine, Ohio, 43311

  • Sanford Joe Lueken Cancer Center

    Bemidji, Minnesota, 56601

  • Southwestern Vermont Medical Center

    Bennington, Vermont, 05201

  • Alta Bates Summit Medical Center-Herrick Campus

    Berkeley, California, 94704

  • Central Vermont Medical Center/National Life Cancer Treatment

    Berlin Corners, Vermont, 05602

  • MacNeal Hospital and Cancer Center

    Berwyn, Illinois, 60402

  • Suburban Hospital

    Bethesda, Maryland, 20814

  • Saint Luke's University Hospital-Bethlehem Campus

    Bethlehem, Pennsylvania, 18015

  • Constantinou, Costas L MD (UIA Investigator)

    Bettendorf, Iowa, 52722

  • University of Iowa Healthcare Cancer Services Quad Cities

    Bettendorf, Iowa, 52722

  • Spectrum Health Big Rapids Hospital

    Big Rapids, Michigan, 49307

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • Northern Rockies Radiation Oncology Center

    Billings, Montana, 59101

  • Saint Vincent Healthcare

    Billings, Montana, 59101

  • Montana Cancer Consortium NCORP

    Billings, Montana, 59102

  • Saint Vincent Frontier Cancer Center

    Billings, Montana, 59102

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Mid Dakota Clinic

    Bismarck, North Dakota, 58501

  • Saint Alexius Medical Center

    Bismarck, North Dakota, 58501

  • Sanford Bismarck Medical Center

    Bismarck, North Dakota, 58501

  • OSF Saint Joseph Medical Center

    Bloomington, Illinois, 61701

  • Illinois CancerCare-Bloomington

    Bloomington, Illinois, 61704

  • IU Health Bloomington

    Bloomington, Indiana, 47408

  • Lynn Regional Cancer Center - West

    Boca Raton, Florida, 33428

  • Boca Raton Comprehensive Cancer Center

    Boca Raton, Florida, 33486

  • Boca Raton Regional Hospital

    Boca Raton, Florida, 33486

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Central Care Cancer Center - Bolivar

    Bolivar, Missouri, 65613

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Boston Medical Center

    Boston, Massachusetts, 02118

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Boulder Community Foothills Hospital

    Boulder, Colorado, 80303

  • Bozeman Health Deaconess Hospital

    Bozeman, Montana, 59715

  • Ocean University Medical Center

    Brick, New Jersey, 08724

  • Dana-Farber Cancer Institute at Boston Medical Center - Brighton

    Brighton, Massachusetts, 02135

  • Wellmont Medical Associates Oncology and Hematology-Bristol

    Bristol, Tennessee, 37620

  • Maimonides Medical Center

    Brooklyn, New York, 11219

  • Coney Island Hospital

    Brooklyn, New York, 11235

  • Bryn Mawr Hospital

    Bryn Mawr, Pennsylvania, 19010

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Providence Saint Joseph Medical Center/Disney Family Cancer Center

    Burbank, California, 91505

  • Mills-Peninsula Medical Center

    Burlingame, California, 94010

  • Lahey Clinic

    Burlington, Massachusetts, 01805

  • Cone Health Cancer Center at Alamance Regional

    Burlington, North Carolina, 27215

  • University of Vermont and State Agricultural College

    Burlington, Vermont, 05405

  • Aurora Cancer Care-Southern Lakes VLCC

    Burlington, Wisconsin, 53105

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • Saint James Community Hospital and Cancer Treatment Center

    Butte, Montana, 59701

  • Cooper Hospital University Medical Center

    Camden, New Jersey, 08103

  • Graham Hospital Association

    Canton, Illinois, 61520

  • Illinois CancerCare-Canton

    Canton, Illinois, 61520

  • Cleveland Clinic Mercy Hospital

    Canton, Ohio, 44708

  • Aultman Health Foundation

    Canton, Ohio, 44710

  • Southeast Missouri Hospital

    Cape Girardeau, Missouri, 63701

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Illinois CancerCare-Carthage

    Carthage, Illinois, 62321

  • Memorial Hospital

    Carthage, Illinois, 62321

  • Waverly Hematology Oncology

    Cary, North Carolina, 27518

  • Rocky Mountain Oncology

    Casper, Wyoming, 82609

  • East Bay Radiation Oncology Center

    Castro Valley, California, 94546

  • Eden Hospital Medical Center

    Castro Valley, California, 94546

  • Valley Medical Oncology Consultants-Castro Valley

    Castro Valley, California, 94546

  • Physicians' Clinic of Iowa PC

    Cedar Rapids, Iowa, 52402

  • Saint Luke's Hospital

    Cedar Rapids, Iowa, 52402

  • Mercy Hospital

    Cedar Rapids, Iowa, 52403

  • Oncology Associates at Mercy Medical Center

    Cedar Rapids, Iowa, 52403

  • Providence Regional Cancer System-Centralia

    Centralia, Washington, 98531

  • Cancer Center of Kansas - Chanute

    Chanute, Kansas, 66720

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Roper Hospital

    Charleston, South Carolina, 29401

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Vandalia Health/CAMC Institute for Academic Medicine

    Charleston, West Virginia, 25304

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina, 28204

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Erlanger Medical Center

    Chattanooga, Tennessee, 37403

  • Saint Luke's Hospital

    Chesterfield, Missouri, 63017

  • Mount Sinai Hospital Medical Center

    Chicago, Illinois, 60608

  • Hematology and Oncology Associates

    Chicago, Illinois, 60611

  • Northwestern University

    Chicago, Illinois, 60611

  • John H Stroger Jr Hospital of Cook County

    Chicago, Illinois, 60612

  • Rush MD Anderson Cancer Center

    Chicago, Illinois, 60612

  • University of Illinois

    Chicago, Illinois, 60612

  • Swedish Covenant Hospital

    Chicago, Illinois, 60625

  • Presence Resurrection Medical Center

    Chicago, Illinois, 60631

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Weiss Memorial Hospital

    Chicago, Illinois, 60640

  • UChicago Medicine Comprehensive Cancer Center - Saint Joseph Hospital

    Chicago, Illinois, 60657

  • Adena Regional Medical Center

    Chillicothe, Ohio, 45601

  • Marshfield Clinic-Chippewa Center

    Chippewa Falls, Wisconsin, 54729

  • The Christ Hospital

    Cincinnati, Ohio, 45219

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • MetroHealth Medical Center

    Cleveland, Ohio, 44109

  • New York Oncology Hematology PC - Clifton Park

    Clifton Park, New York, 12065

  • Finger Lakes Hematology and Oncology

    Clifton Springs, New York, 14432

  • UI Health Care Mission Cancer and Blood - West Des Moines Clinic

    Clive, Iowa, 50325

  • Penrose-Saint Francis Healthcare

    Colorado Springs, Colorado, 80907

  • UCHealth Memorial Hospital Central

    Colorado Springs, Colorado, 80909

  • Veterans Administration

    Columbia, Missouri, 65201

  • MU Health - University Hospital/Ellis Fischel Cancer Center

    Columbia, Missouri, 65212

  • John B Amos Cancer Center

    Columbus, Georgia, 31904

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Columbus NCI Community Oncology Research Program

    Columbus, Ohio, 43215

  • Grant Medical Center

    Columbus, Ohio, 43215

  • Mount Carmel Health Center West

    Columbus, Ohio, 43222

  • Doctors Hospital

    Columbus, Ohio, 43228

  • New Hampshire Oncology Hematology PA-Concord

    Concord, New Hampshire, 03301

  • Atrium Health Cabarrus/LCI-Concord

    Concord, North Carolina, 28025

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Mary Imogene Bassett Hospital

    Cooperstown, New York, 13326

  • Bay Area Hospital

    Coos Bay, Oregon, 97420

  • Heartland Oncology and Hematology LLP

    Council Bluffs, Iowa, 51503

  • Ochsner Health Center-Covington

    Covington, Louisiana, 70433

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • Parkland Memorial Hospital

    Dallas, Texas, 75235

  • Clements University Hospital

    Dallas, Texas, 75390

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Danbury Hospital

    Danbury, Connecticut, 06810

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Mercy Fitzgerald Hospital

    Darby, Pennsylvania, 19023-1291

  • MercyOne Genesis Davenport Medical Center

    Davenport, Iowa, 52803

  • MercyOne Genesis Davenport Cancer Center

    Davenport, Iowa, 52804

  • Grandview Hospital

    Dayton, Ohio, 45405

  • Good Samaritan Hospital - Dayton

    Dayton, Ohio, 45406

  • Miami Valley Hospital

    Dayton, Ohio, 45409

  • Miami Valley Hospital North

    Dayton, Ohio, 45415

  • Dayton Veterans Affairs Medical Center

    Dayton, Ohio, 45428

  • Dayton NCI Community Oncology Research Program

    Dayton, Ohio, 45459

  • Halifax Health Cancer Center for Hope - Daytona Beach

    Daytona Beach, Florida, 32114

  • Corewell Health Dearborn Hospital

    Dearborn, Michigan, 48124

  • Emory Decatur Hospital

    Decatur, Georgia, 30033

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Heartland Cancer Research NCORP

    Decatur, Illinois, 62526

  • Broward Health North

    Deerfield Beach, Florida, 33064

  • Grady Memorial Hospital

    Delaware, Ohio, 43015

  • Kaiser Permanente-Franklin

    Denver, Colorado, 80205

  • AdventHealth Porter

    Denver, Colorado, 80210

  • Presbyterian - Saint Lukes Medical Center - Health One

    Denver, Colorado, 80218

  • Saint Joseph Hospital - Cancer Centers of Colorado

    Denver, Colorado, 80218

  • Rose Medical Center

    Denver, Colorado, 80220

  • Western States Cancer Research NCORP

    Denver, Colorado, 80222

  • Mercy Capitol

    Des Moines, Iowa, 50307

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • Iowa-Wide Oncology Research Coalition NCORP

    Des Moines, Iowa, 50309

  • UI Health Care Mission Cancer and Blood - Des Moines Clinic

    Des Moines, Iowa, 50309

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • UI Health Care Mission Cancer and Blood - Laurel Clinic

    Des Moines, Iowa, 50314

  • Iowa Lutheran Hospital

    Des Moines, Iowa, 50316

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Henry Ford Health Saint John Hospital

    Detroit, Michigan, 48236

  • Cancer Center of Kansas - Dodge City

    Dodge City, Kansas, 67801

  • Bayhealth Hospital Kent Campus

    Dover, Delaware, 19901

  • Wentworth-Douglass Hospital

    Dover, New Hampshire, 03820

  • Doylestown Hospital

    Doylestown, Pennsylvania, 18901

  • Delaware County Memorial Hospital

    Drexel Hill, Pennsylvania, 19026

  • Oncology Hematology Associates of Northern Pennsylvania

    DuBois, Pennsylvania, 15801

  • Essentia Health Cancer Center

    Duluth, Minnesota, 55805

  • Essentia Health Saint Mary's Medical Center

    Duluth, Minnesota, 55805

  • Miller-Dwan Hospital

    Duluth, Minnesota, 55805

  • Saint Luke's Hospital of Duluth

    Duluth, Minnesota, 55805

  • Pocono Medical Center

    East Stroudsburg, Pennsylvania, 18301

  • Hematology Oncology Associates of Central New York-East Syracuse

    East Syracuse, New York, 13057

  • University of Maryland Shore Medical Center at Easton

    Easton, Maryland, 21601

  • Easton Hospital

    Easton, Pennsylvania, 18042

  • HSHS Sacred Heart Hospital

    Eau Claire, Wisconsin, 54701

  • Marshfield Clinic Cancer Center at Sacred Heart

    Eau Claire, Wisconsin, 54701

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Cancer Center of Kansas - El Dorado

    El Dorado, Kansas, 67042

  • Advocate Sherman Hospital

    Elgin, Illinois, 60123

  • Ascension Alexian Brothers - Elk Grove Village

    Elk Grove Village, Illinois, 60007

  • Elkhart Clinic

    Elkhart, Indiana, 46514-2098

  • Michiana Hematology Oncology PC-Elkhart

    Elkhart, Indiana, 46514

  • Elkhart General Hospital

    Elkhart, Indiana, 46515

  • Christiana Care - Union Hospital

    Elkton, Maryland, 21921

  • Elmhurst Memorial Hospital

    Elmhurst, Illinois, 60126

  • Elmhurst Hospital Center

    Elmhurst, New York, 11373

  • Arnot Ogden Medical Center/Falck Cancer Center

    Elmira, New York, 14905

  • Bay Area Breast Surgeons Inc

    Emeryville, California, 94608

  • Swedish Medical Center

    Englewood, Colorado, 80113

  • Englewood Hospital and Medical Center

    Englewood, New Jersey, 07631

  • Ephrata Cancer Center

    Ephrata, Pennsylvania, 17522

  • UPMC Hillman Cancer Center Erie

    Erie, Pennsylvania, 16505

  • Saint Vincent Hospital

    Erie, Pennsylvania, 16544

  • OSF Saint Francis Hospital and Medical Group

    Escanaba, Michigan, 49829

  • Eureka Hospital

    Eureka, Illinois, 61530

  • Illinois CancerCare-Eureka

    Eureka, Illinois, 61530

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • Saint Francis Hospital

    Evanston, Illinois, 60202

  • Exeter Hospital

    Exeter, New Hampshire, 03833

  • Inova Schar Cancer Institute

    Fairfax, Virginia, 22031

  • Essentia Health Cancer Center-South University Clinic

    Fargo, North Dakota, 58103

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Saint Francis Hospital

    Federal Way, Washington, 98003

  • Etzell, Paul S MD (UIA Investigator)

    Fergus Falls, Minnesota, 56537

  • Lake Region Healthcare Corporation-Cancer Care

    Fergus Falls, Minnesota, 56537

  • Swenson, Wade II, MD (UIA Investigator)

    Fergus Falls, Minnesota, 56537

  • Blanchard Valley Hospital

    Findlay, Ohio, 45840

  • Hunterdon Medical Center

    Flemington, New Jersey, 08822

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Genesys Regional Medical Center-West Flint Campus

    Flint, Michigan, 48532

  • McLeod Regional Medical Center

    Florence, South Carolina, 29506

  • Saint Agnes Hospital/Agnesian Cancer Center

    Fond du Lac, Wisconsin, 54935

  • Poudre Valley Hospital

    Fort Collins, Colorado, 80524

  • Eisenhower Army Medical Center

    Fort Eisenhower, Georgia, 30905

  • Holy Cross Hospital

    Fort Lauderdale, Florida, 33308

  • Broward Health Medical Center

    Fort Lauderdale, Florida, 33316

  • Brooke Army Medical Center

    Fort Sam Houston, Texas, 78234

  • Cancer Center of Kansas - Fort Scott

    Fort Scott, Kansas, 66701

  • Mercy Hospital Fort Smith

    Fort Smith, Arkansas, 72903

  • Fort Wayne Medical Oncology and Hematology Inc-Parkview

    Fort Wayne, Indiana, 46845

  • MetroWest Medical Center-Framingham Union Hospital

    Framingham, Massachusetts, 01702

  • Atrium Medical Center-Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Vanderbilt-Ingram Cancer Center Cool Springs

    Franklin, Tennessee, 37067

  • Aurora Cancer Care-Franklin

    Franklin, Wisconsin, 53132

  • Frederick Memorial Hospital

    Frederick, Maryland, 21701

  • Kaiser Permanente-Fremont

    Fremont, California, 94538

  • Valley Medical Oncology Consultants-Fremont

    Fremont, California, 94538

  • Washington Health

    Fremont, California, 94538

  • California Cancer Associates for Research and Excellence (cCare)

    Fresno, California, 93720

  • Unity Hospital

    Fridley, Minnesota, 55432

  • Florida Cancer Specialists-Gainesville Cancer Center

    Gainesville, Florida, 32605

  • Northeast Georgia Medical Center-Gainesville

    Gainesville, Georgia, 30501

  • Galesburg Cottage Hospital

    Galesburg, Illinois, 61401

  • Illinois CancerCare-Cottage

    Galesburg, Illinois, 61401

  • Illinois CancerCare-Galesburg

    Galesburg, Illinois, 61401

  • Aurora Health Care Germantown Health Center

    Germantown, Wisconsin, 53022

  • Glendale Memorial Hospital and Health Center

    Glendale, California, 91204

  • Aurora Cancer Care-Glendale

    Glendale, Wisconsin, 53212

  • Addison Gilbert Hospital

    Gloucester, Massachusetts, 01930

  • Peninsula Cancer Institute-Gloucester

    Gloucester, Virginia, 23061

  • Southeastern Medical Oncology Center-Goldsboro

    Goldsboro, North Carolina, 27534

  • Wayne Memorial Hospital

    Goldsboro, North Carolina, 27534

  • Goshen Center for Cancer Care

    Goshen, Indiana, 46526

  • Altru Cancer Center

    Grand Forks, North Dakota, 58201

  • Saint Mary's Hospital and Regional Medical Center

    Grand Junction, Colorado, 81501

  • Cancer Research Consortium of West Michigan NCORP

    Grand Rapids, Michigan, 49503

  • Corewell Health Grand Rapids Hospitals - Butterworth Hospital

    Grand Rapids, Michigan, 49503

  • Trinity Health Grand Rapids Hospital

    Grand Rapids, Michigan, 49503

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Peru1 site

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South Africa1 site

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About this study

Official title: A Double-Blind Phase III Trial of Doxorubicin and Cyclophosphamide Followed by Paclitaxel With Bevacizumab or Placebo in Patients With Lymph Node Positive and High Risk Lymph Node Negative Breast Cancer

This randomized phase III trial studies doxorubicin hydrochloride, cyclophosphamide, and paclitaxel to see how well they work with or without bevacizumab in treating patients with cancer that has spread to the lymph nodes (lymph node-positive) or cancer that has not spread to the lymph nodes but is at high risk for returning (high-risk, lymph node-negative breast cancer). Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of breast cancer by blocking blood flow to the tumor. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery and help prevent the tumor from returning. It is not yet known whether doxorubicin hydrochloride, cyclophosphamide, and paclitaxel are more effective with or without bevacizumab.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the disease-free survival of patients (defined as invasive disease-free survival [IFDS]) with lymph node positive and high risk lymph node negative breast cancer randomized to treatment with either doxorubicin (doxorubicin hydrochloride)/cyclophosphamide plus placebo followed by paclitaxel (AC + placebo > T + placebo) or the same chemotherapy regimen plus bevacizumab.

SECONDARY OBJECTIVES:

  1. To compare short-term (20-24 weeks) versus long-term (50-54 weeks) bevacizumab therapy.

II. To compare the overall survival. III. To evaluate toxicity. IV. To evaluate the association between outcomes in E5103 (disease-free survival, overall survival and toxicities) and genotype (derived from candidate single nucleotide polymorphisms and genome wide evaluations).

  1. To compare the quality of life of breast cancer patients treated with AC/paclitaxel and bevacizumab or placebo, in terms of physical symptoms, physical functioning, psychological state and social functioning over an 18 month period.

VI. To determine the impact of theoretical biomarker information on patients' willingness to accept the toxicities of bevacizumab for the estimated potential benefit.

VII. To create a biospecimen repository including plasma, serum and CellSearch cassettes containing circulating tumor cells (CTC) for evaluating determinants of late relapse, including candidate biomarkers reflecting occult tumor burden (e.g., CTCs and plasma tumor deoxyribonucleic acid [DNA]) and host factors (e.g., estrogen, insulin-insulin-like growth factor [IGF] axis, inflammation, etc).

VIII. To create a biorepository of metastatic tumor samples in patients who have had a late relapse.

IX. To determine body mass index (BMI) and comorbidity burden in patients with operable breast cancer five or more years after diagnosis.

  1. To determine whether there is a relationship between late relapse and BMI at diagnosis and at 5 years after diagnosis, and whether BMI-associated inflammatory and/or metabolic biomarkers are associated with early and late recurrence.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive doxorubicin hydrochloride intravenously (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.

ARM II: 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.

ARM III: 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.

In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 15 years.

Being tested
Bevacizumab, Cyclophosphamide, Doxorubicin Hydrochloride, Laboratory Biomarker Analysis, Paclitaxel

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BevacizumabBiological

    Also called ABP 215, ABP-215, ABP215, Alymsys

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518

    Given IV

  • Doxorubicin HydrochlorideDrug

    Also called 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Given IV

  • Placebo AdministrationOther

    Given IV

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies (closed as of 5/28/10)

Study groups in NCT00433511
Study groupRoleWhat they receive
Arm I (chemotherapy, placebo)Active comparatorPatients 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.
Receives: Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Other: Placebo Administration; Other: Quality-of-Life Assessment
Arm II (chemotherapy, bevacizumab)ExperimentalPatients 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.
Receives: Biological: Bevacizumab; Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Other: Quality-of-Life Assessment
Arm III (chemotherapy, bevacizumab monotherapy)ExperimentalPatients 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.
Receives: Biological: Bevacizumab; Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Other: Quality-of-Life Assessment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Invasive Disease-free Survival (IDFS) Rate at 5 Years

    Invasive disease-free survival (IDFS) was defined as time from from date of randomization to first treatment failure (invasive ipsilateral, local/regional, or distant recurrence, invasive contralateral breast cancer, invasive non-breast second primary malignancy or death from any cause, whichever occurred first). Cases with incomplete follow-up, without documented IDFS event including those who developed squamous or basal cell skin cancers or insitu carcinomas of any site as their only event were censored at the date of last disease evaluation.

    Measured: Assessed at 5 years

Secondary outcomes (2)

  1. 5-year Overall Survival (OS)

    Overall survival (OS) was defined as time from date of randomization to death from any cause, otherwise cases were censored at date last known to be alive.

    Measured: Assessed at 5 years

  2. The Association Between IDFS and Genotype

    Invasive disease-free survival (IDFS) is defined as time from from date of randomization to first treatment failure (invasive ipsilateral, local/regional, or distant recurrence, invasive contralateral breast cancer, invasive non-breast second primary malignancy or death from any cause, whichever occurred first). Cases with incomplete follow-up, without documented IDFS event including those who developed squamous or basal cell skin cancers or insitu carcinomas of any site as their only event were censored at the date of last disease evaluation. Three-year IDFS rate was reported by genetic ancestry and IDFS was compared between patients with European ancestry and patients with African ancestry.

    Measured: Assessed at 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2007 (estimated)
  2. Study start2 Nov 2007
  3. Primary completion7 Jan 2014
  4. Study completion20 Feb 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
4,994 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00433511
Sponsor's protocol ID
NCI-2009-00561
Other IDs
NCI-2009-00561, CDR0000528955, E5103, ECOG-E5103, 07-963, E5103, E5103, U10CA180820
Status last verified
Aug 2026
First submitted
8 Feb 2007
Last updated
1 Oct 2026
Data monitoring committee
No

Publications

  • Rosenberg SM, O'Neill A, Sepucha K, Miller KD, Dang CT, Northfelt DW, Sledge GW, Schneider BP, Partridge AH. Quality of Life Following Receipt of Adjuvant Chemotherapy With and Without Bevacizumab in Patients With Lymph Node-Positive and High-Risk Lymph Node-Negative Breast Cancer. JAMA Netw Open. 2022 Feb 1;5(2):e220254. doi: 10.1001/jamanetworkopen.2022.0254.

    PubMed 35226083

  • Ip EH, Saldana S, Miller KD, Carlos RC, Gareen IF, Sparano JA, Graham N, Zhao F, Lee JW, O'Connell NS, Cella D, Peipert JD, Gray RJ, Wagner LI. Tolerability of bevacizumab and chemotherapy in a phase 3 clinical trial with human epidermal growth factor receptor 2-negative breast cancer: A trajectory analysis of adverse events. Cancer. 2021 Dec 15;127(24):4546-4556. doi: 10.1002/cncr.33992. Epub 2021 Nov 2.

    PubMed 34726788

  • Sparano J, O'Neill A, Alpaugh K, Wolff AC, Northfelt DW, Dang CT, Sledge GW, Miller KD. Association of Circulating Tumor Cells With Late Recurrence of Estrogen Receptor-Positive Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2018 Dec 1;4(12):1700-1706. doi: 10.1001/jamaoncol.2018.2574.

    PubMed 30054636

  • Miller KD, O'Neill A, Gradishar W, Hobday TJ, Goldstein LJ, Mayer IA, Bloom S, Brufsky AM, Tevaarwerk AJ, Sparano JA, Le-Lindqwister NA, Hendricks CB, Northfelt DW, Dang CT, Sledge GW Jr. Double-Blind Phase III Trial of Adjuvant Chemotherapy With and Without Bevacizumab in Patients With Lymph Node-Positive and High-Risk Lymph Node-Negative Breast Cancer (E5103). J Clin Oncol. 2018 Sep 1;36(25):2621-2629. doi: 10.1200/JCO.2018.79.2028. Epub 2018 Jul 24.

    PubMed 30040523

  • Partridge AH, Sepucha K, O'Neill A, Miller KD, Baker E, Dang CT, Northfelt DW, Sledge GW, Schneider BP. Does biomarker information impact breast cancer patients' preferences and physician recommendation for adjuvant chemotherapy? Breast Cancer Res Treat. 2017 Oct;165(3):545-553. doi: 10.1007/s10549-017-4338-x. Epub 2017 Jun 23.

    PubMed 28646344

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