AzTrials
AzTrials

Invasive Breast CarcinomaPhase 3NCT00601900

Tamoxifen Citrate or Letrozole With or Without Bevacizumab in Treating Women With Stage IIIB or Stage IV Breast Cancer

A Phase 3 study testing Bevacizumab, Laboratory Biomarker Analysis and Letrozole in people with Invasive Breast Carcinoma and Recurrent Breast Carcinoma, run by National Cancer Institute (NCI) at 522 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This randomized phase III trial studies tamoxifen citrate or letrozole together with bevacizumab to see how well it works compared with tamoxifen citrate or letrozole alone in treating women with stage IIIB or stage IV breast cancer. Estrogen can cause the growth of breast cancer cells. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Bevacizumab, Laboratory Biomarker Analysis and Letrozole
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
394 participants
Where
522 sitesin 2 countries
Study dates
24 Sep 2008to 29 Jan 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologic confirmation of invasive cancer of the female breast in either the primary or metastatic setting
  • Stage IV disease or stage IIIB disease (using American Joint Committee on Cancer [AJCC] criteria, 6th edition) not amenable to local therapy
  • Patients may not have a "currently active" second malignancy other than non-melanoma skin cancers; patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse
  • Tumors (from either primary or metastatic sites) must express estrogen receptor (ER) and/or progesterone receptor (PgR) in >= 1% of cells will be considered positive
  • Postmenopausal women are eligible for this trial; before study registration, menopausal status must be defined according to the criteria below:
  • Age >= 55 years and one year or more of amenorrhea
Show all 62Show fewer
  • Age < 55 years and one year or more of amenorrhea, with an estradiol assay < 20 pg/ml
  • For women age < 55 with prior hysterectomy but intact ovaries, with an estradiol assay < 20 pg/ml
  • Surgical menopause with bilateral oophorectomy (at least 28 days must elapse from surgery to time of study registration)
  • Ovarian suppression on a luteinizing hormone-releasing hormone (LH-RH) agonist
  • Premenopausal women who do not meet the postmenopausal criteria above are also eligible, but are required to undergo ovarian suppression; this can be initiated any time prior to or on day 1 of protocol therapy, regardless of chosen endocrine therapy, and will continue for the duration of protocol therapy
  • Patients must have measurable or non-measurable disease by RECIST criteria, with radiologic scans within 28 days of study registration
  • Measurable disease: lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 2.0 cm with conventional techniques or as >= 1.0 cm with spiral computed tomography (CT) scan
  • Non-measurable disease: all other lesions, including small lesions (longest diameter < 2.0 cm with conventional techniques or < 1.0 cm with spiral CT scan) and truly non-measurable lesions
  • Lesions that are considered non-measurable include the following:
  • Bone lesions
  • Leptomeningeal disease
  • Ascites
  • Pleural/pericardial effusion
  • Inflammatory breast disease
  • Abdominal masses that are not confirmed and followed by imaging techniques
  • Cystic lesions
  • Prior endocrine therapy is not required
  • Prior endocrine therapy in the metastatic setting is not permitted (unless tamoxifen or an aromatase inhibitor was initiated within 4 weeks prior to registration to facilitate enrollment of patients who recently started first-line endocrine therapy for metastatic breast cancer); if prior letrozole therapy was initiated within the past 4 weeks, the patients should remain on letrozole as the study therapy; patients who began therapy with tamoxifen, anastrozole or exemestane must switch to letrozole to be eligible to participate in this study
  • Prior endocrine therapy in the adjuvant setting is permitted; there is no time restriction for how long the patient must be on the adjuvant endocrine therapy, nor is there a time restriction for how long the patient needs to be off prior adjuvant endocrine therapy before beginning protocol therapy on 40503
  • Prior treatment with ovarian suppression is allowed in either the adjuvant or metastatic setting; if medical ovarian suppression is being administered it can be initiated any time prior to or at the start of protocol therapy, and continued throughout the duration of the trial; surgical castration with bilateral oophorectomy must be performed at least 28 days prior to study registration (due to concerns of poor wound healing on bevacizumab)
  • Patients may not have received any prior anti-VEGF or VEGFR tyrosine kinase inhibitor therapy
  • Prior radiotherapy must have been completed and all toxicities resolved at least two weeks prior to registration
  • Chemotherapy in the adjuvant or neoadjuvant setting is permitted; at least twelve months prior to registration must have elapsed since the completion of adjuvant or neoadjuvant chemotherapy and all toxicities must have resolved; taxane-related neurotoxicity must have resolved to sensory grade < 2 and no motor neuropathy of any grade is allowed
  • Patients may have received one prior chemotherapy regimen for metastatic disease; the final dose of prior chemotherapy must have been administered at least 3 weeks prior to study registration
  • Treatment with bisphosphonates is allowed and recommended as per American Society of Clinical Oncology (ASCO) guidelines
  • Patients must not have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study registration, and must have fully recovered from any such procedure
  • Patients must not have anticipation of need for major surgical procedure during the course of the study
  • Patients must not have had a core biopsy or other minor surgical procedure, within 7 days prior to study registration; placement of a vascular access device is allowed within 7 days of registration
  • Patients must not have a history of abdominal fistula, or intra-abdominal abscess within 6 months prior to study registration
  • Patients with a history of gastrointestinal (GI) perforation within 12 months prior to registration are not eligible
  • Patients with a history of significant bleeding episodes (e.g., hemoptysis, upper or lower GI bleeding) within 6 months prior to registration are not eligible
  • Patients must not have clinically significant cardiovascular disease that includes the following:
  • Uncontrolled hypertension defined as systolic blood pressure > 150 and/or diastolic blood pressure > 90 mmHg on antihypertensive medications or any prior history of hypertensive crisis or hypertensive encephalopathy
  • History of myocardial infarction or unstable angina within past 6 months
  • New York Heart Association (NYHA) grade 2 or greater congestive heart failure
  • Symptomatic peripheral vascular disease
  • Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or arterial thrombotic events
  • Full dose anticoagulation therapy is allowed for the treatment of prior conditions such as venous thrombosis or atrial fibrillation, but not for the treatment of prior arterial thrombotic events; patients on full dose anticoagulants must be on a stable dose of warfarin and have an in-range international normalized ratio (INR) (usually between 2 and 3) or be on a stable dose of low-molecular weight (LMW) heparin; patients receiving antiplatelet agents are eligible, as are patients on daily prophylactic aspirin or anticoagulation for atrial fibrillation
  • Patients may not have a history of stroke or transient ischemic attack within 6 months prior to study registration
  • Patients with a history of seizures must be well controlled with standard medication
  • Patients must not have known central nervous system (CNS) metastases or leptomeningeal disease (screening with brain imaging is not required for asymptomatic patients)
  • In aromatase inhibitor (AI)-treated patients: no known allergies to imidazole drugs, (e.g. clotrimazole, ketoconazole, miconazole, econazole, sulconazole, tioconazole, or terconazole) or compounds structurally similar to bevacizumab
  • In tamoxifen treated patients: no known allergies to selective estrogen receptor modulators (e.g. tamoxifen, raloxifene or toremifene) or compounds structurally similar to bevacizumab; for patients enrolled after Update #5, endocrine therapy will consist of letrozole only and this criterion will no longer apply
  • Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status =< 1
  • No serious, non-healing wound, ulcer, or bone fracture
  • Life expectancy of >= 12 weeks
  • All patients who are premenopausal (if not already receiving ovarian suppression therapy/surgical oophorectomy) must have a negative beta-human chorionic gonadotropin (beta-Hcg) prior to starting on study treatment; patients may not be pregnant or nursing at any time during the study; ovarian suppression is required in women of childbearing potential by the start of protocol therapy, and will continue for the duration of protocol therapy
  • Granulocytes >= 1,000/ul
  • Platelet count >= 100,000/ul
  • Creatinine =< 2.0 mg/dL
  • Bilirubin =< 1.5 times upper limit of normal (ULN) unless due to Gilbert's syndrome
  • Transaminases (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) =< 2.5 times ULN
  • International normalized ratio (INR) =< 1.6, unless on full dose warfarin
  • Beta-Hcg negative in premenopausal women
  • Urine protein =< 1+ or urine to plasma creatinine (UPC) < 1
  • Patients discovered to have >= 2+ proteinuria at baseline must undergo a 24-hour urine collection that must demonstrate < 1 g of protein/24 hr, or UPC ratio < 1 to allow participation in the study

Who cannot join

None listed.

Trial locations and contacts

522 sites in 2 countries.

301 sites in 2 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

  • 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

  • AnMed Health Cancer Center

    Anderson, South Carolina, 29621

  • 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

  • Langlade Hospital and Cancer Center

    Antigo, Wisconsin, 54409

  • East Bay Medical Oncology Hematology Medical Associates-Antioch

    Antioch, California, 94531

  • Randolph Hospital

    Asheboro, North Carolina, 27203

  • Our Lady Bellefonte Hospital

    Ashland, Kentucky, 41101

  • University Cancer and Blood Center LLC

    Athens, Georgia, 30607

  • Piedmont Hospital

    Atlanta, Georgia, 30309

  • Atlanta Regional CCOP

    Atlanta, Georgia, 30342

  • Emory Saint Joseph's Hospital

    Atlanta, Georgia, 30342

  • Northside Hospital

    Atlanta, Georgia, 30342

  • 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

  • Veterans Administration Medical Center-Baltimore

    Baltimore, Maryland, 21201

  • Greater Baltimore Medical Center

    Baltimore, Maryland, 21204

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Hematology/Oncology Clinic PLLC

    Baton Rouge, Louisiana, 70809

  • Mary Bird Perkins Cancer Center

    Baton Rouge, Louisiana, 70809

  • Ochsner Health Center-Summa

    Baton Rouge, Louisiana, 70809

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

  • McLaren Cancer Institute-Bay City

    Bay City, Michigan, 48706

  • Franciscan Saint Francis Health-Beech Grove

    Beech Grove, Indiana, 46107

  • Mary Rutan Hospital

    Bellefontaine, Ohio, 43311

  • Saint Charles Health System

    Bend, Oregon, 97701

  • Alta Bates Summit Medical Center-Herrick Campus

    Berkeley, California, 94704

  • 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

  • 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

  • Boca Raton Regional Hospital

    Boca Raton, Florida, 33486

  • Central Care Cancer Center - Bolivar

    Bolivar, Missouri, 65613

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Boulder Community Hospital

    Boulder, Colorado, 80301

  • Bozeman Health Deaconess Hospital

    Bozeman, Montana, 59715

  • Cox Cancer Center Branson

    Branson, Missouri, 65616

  • Bryn Mawr Hospital

    Bryn Mawr, Pennsylvania, 19010

  • Providence Saint Joseph Medical Center/Disney Family Cancer Center

    Burbank, California, 91505

  • Mills-Peninsula Medical Center

    Burlingame, California, 94010

  • Aurora Cancer Care-Southern Lakes VLCC

    Burlington, Wisconsin, 53105

  • 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

  • Aultman Health Foundation

    Canton, Ohio, 44710

  • Southeast Missouri Hospital

    Cape Girardeau, Missouri, 63701

  • Mercy Cancer Center - Cape Girardeau

    Cape Girardeau, Missouri, 63703

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Illinois CancerCare-Carthage

    Carthage, Illinois, 62321

  • Memorial Hospital

    Carthage, Illinois, 62321

  • 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

  • Providence Regional Cancer System-Centralia

    Centralia, Washington, 98531

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • West Virginia University Charleston Division

    Charleston, West Virginia, 25304

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Sentara Martha Jefferson Hospital

    Charlottesville, Virginia, 22901

  • Erlanger Medical Center

    Chattanooga, Tennessee, 37403

  • Mount Sinai Hospital Medical Center

    Chicago, Illinois, 60608

  • John H Stroger Jr Hospital of Cook County

    Chicago, Illinois, 60612

  • Mercy Hospital and Medical Center

    Chicago, Illinois, 60616

  • Presence Resurrection Medical Center

    Chicago, Illinois, 60631

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Advocate Illinois Masonic Medical Center

    Chicago, Illinois, 60657

  • Adventist Health Cancer Care Center Chico

    Chico, California, 95973

  • Adena Regional Medical Center

    Chillicothe, Ohio, 45601

  • Marshfield Clinic-Chippewa Center

    Chippewa Falls, Wisconsin, 54729

  • Clackamas Radiation Oncology Center

    Clackamas, Oregon, 97015

  • MetroHealth Medical Center

    Cleveland, Ohio, 44109

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

    Clive, Iowa, 50325

  • Community Cancer Institute

    Clovis, California, 93611

  • Penrose-Saint Francis Healthcare

    Colorado Springs, Colorado, 80907

  • 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

  • Ochsner Health Center-Covington

    Covington, Louisiana, 70433

  • Hematology and Oncology Associates of Rhode Island Inc

    Cranston, Rhode Island, 02920

  • Danville Regional Medical Center

    Danville, Virginia, 24541

  • 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

  • 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

  • Grady Memorial Hospital

    Delaware, Ohio, 43015

  • 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

  • Advocate Good Samaritan Hospital

    Downers Grove, Illinois, 60515

  • Doylestown Hospital

    Doylestown, Pennsylvania, 18901

  • Dublin Hematology Oncology Care PC

    Dublin, Georgia, 31021

  • Essentia Health Cancer Center

    Duluth, Minnesota, 55805

  • Essentia Health Saint Mary's Medical Center

    Duluth, Minnesota, 55805

  • Miller-Dwan Hospital

    Duluth, Minnesota, 55805

  • Michigan State University Clinical Center

    East Lansing, Michigan, 48824

  • Hematology Oncology Associates of Central New York-East Syracuse

    East Syracuse, New York, 13057

  • Marshfield Clinic Cancer Center at Sacred Heart

    Eau Claire, Wisconsin, 54701

  • 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

  • OSF Saint Francis Hospital and Medical Group

    Escanaba, Michigan, 49829

  • Eureka Hospital

    Eureka, Illinois, 61530

  • Illinois CancerCare-Eureka

    Eureka, Illinois, 61530

  • Kaiser Permanente - Fair Oaks Medical Center

    Fairfax, Virginia, 22033

  • Piedmont Fayette Hospital

    Fayetteville, Georgia, 30214

  • Saint Francis Hospital

    Federal Way, Washington, 98003

  • Etzell, Paul S MD (UIA Investigator)

    Fergus Falls, Minnesota, 56537

  • Swenson, Wade II, MD (UIA Investigator)

    Fergus Falls, Minnesota, 56537

  • Blanchard Valley Hospital

    Findlay, Ohio, 45840

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Genesys Regional Medical Center-West Flint Campus

    Flint, Michigan, 48532

  • McLaren Cancer Institute-Flint

    Flint, Michigan, 48532

  • McLeod Regional Medical Center

    Florence, South Carolina, 29506

  • Poudre Valley Hospital

    Fort Collins, Colorado, 80524

  • Eisenhower Army Medical Center

    Fort Eisenhower, Georgia, 30905

  • Holy Cross Hospital

    Fort Lauderdale, Florida, 33308

  • Sparks Regional Medical Center

    Fort Smith, Arkansas, 72901

  • Fort Wayne Medical Oncology and Hematology Inc-Parkview

    Fort Wayne, Indiana, 46845

  • Atrium Medical Center-Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Aurora Cancer Care-Franklin

    Franklin, Wisconsin, 53132

  • Frederick Memorial Hospital

    Frederick, Maryland, 21701

  • CentraState Medical Center

    Freehold, New Jersey, 07728

  • Freeport Memorial Hospital/Leonard C Ferguson Cancer Center

    Freeport, Illinois, 61032

  • Valley Medical Oncology Consultants-Fremont

    Fremont, California, 94538

  • Florida Cancer Specialists-Gainesville Cancer Center

    Gainesville, Florida, 32605

  • Northeast Georgia Medical Center-Gainesville

    Gainesville, Georgia, 30501

  • Illinois CancerCare-Galesburg

    Galesburg, Illinois, 61401

  • Aurora Health Care Germantown Health Center

    Germantown, Wisconsin, 53022

  • Aurora Cancer Care-Glendale

    Glendale, Wisconsin, 53212

  • Adirondack Cancer Center

    Glens Falls, New York, 12801

  • Addison Gilbert Hospital

    Gloucester, Massachusetts, 01930

  • Wayne Memorial Hospital

    Goldsboro, North Carolina, 27534

  • Altru Cancer Center

    Grand Forks, North Dakota, 58201

  • Nebraska Cancer Specialists/Oncology Hematology West PC

    Grand Island, Nebraska, 68803

  • 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

  • Benefis Sletten Cancer Institute

    Great Falls, Montana, 59405

  • Berdeaux, Donald MD (UIA Investigator)

    Great Falls, Montana, 59405

  • Great Falls Clinic

    Great Falls, Montana, 59405

  • Banner North Colorado Medical Center

    Greeley, Colorado, 80631

  • Green Bay Oncology at Saint Vincent Hospital

    Green Bay, Wisconsin, 54301-3526

  • Bellin Memorial Hospital

    Green Bay, Wisconsin, 54301

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin, 54301

  • Saint Vincent Hospital Cancer Center at Saint Mary's

    Green Bay, Wisconsin, 54303

  • Aurora BayCare Medical Center

    Green Bay, Wisconsin, 54311

  • Marin General Hospital

    Greenbrae, California, 94904

  • Cone Health Cancer Center

    Greensboro, North Carolina, 27403

  • Wayne Hospital

    Greenville, Ohio, 45331

  • Saint Francis Hospital

    Greenville, South Carolina, 29601

  • Legacy Mount Hood Medical Center

    Gresham, Oregon, 97030

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Meritus Medical Center

    Hagerstown, Maryland, 21742

  • Hartford Hospital

    Hartford, Connecticut, 06102

  • Smilow Cancer Hospital Care Center at Saint Francis

    Hartford, Connecticut, 06105

  • Ingalls Memorial Hospital

    Harvey, Illinois, 60426

  • Illinois CancerCare-Havana

    Havana, Illinois, 62644

  • Mason District Hospital

    Havana, Illinois, 62644

  • Northern Montana Hospital

    Havre, Montana, 59501

  • HaysMed

    Hays, Kansas, 67601

  • Saint Peter's Community Hospital

    Helena, Montana, 59601

  • Hawaii Cancer Care Inc - Waterfront Plaza

    Honolulu, Hawaii, 96813

  • Queen's Medical Center

    Honolulu, Hawaii, 96813

  • Straub Clinic and Hospital

    Honolulu, Hawaii, 96813

  • University of Hawaii Cancer Center

    Honolulu, Hawaii, 96813

  • Queen's Cancer Center - Kuakini

    Honolulu, Hawaii, 96817

  • The Cancer Center of Hawaii-Liliha

    Honolulu, Hawaii, 96817

  • Kapiolani Medical Center for Women and Children

    Honolulu, Hawaii, 96826

  • Hutchinson Regional Medical Center

    Hutchinson, Kansas, 67502

  • Cape Cod Hospital

    Hyannis, Massachusetts, 02601

  • Ascension Saint Vincent Indianapolis Hospital

    Indianapolis, Indiana, 46260

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Allegiance Health

    Jackson, Michigan, 49201

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Queens Hospital Center

    Jamaica, New York, 11432

  • Mercyhealth Hospital and Cancer Center - Janesville

    Janesville, Wisconsin, 53548

  • MU Health Care Goldschmidt Cancer Center

    Jefferson City, Missouri, 65109

  • Duly Health and Care Joliet

    Joliet, Illinois, 60435

  • Freeman Health System

    Joplin, Missouri, 64804

  • Jupiter Medical Center

    Jupiter, Florida, 33458

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • Ascension Borgess Hospital

    Kalamazoo, Michigan, 49048

  • Glacier Oncology PLLC

    Kalispell, Montana, 59901

  • Kalispell Medical Oncology

    Kalispell, Montana, 59901

  • Logan Health Medical Center

    Kalispell, Montana, 59901

  • Presence Saint Mary's Hospital

    Kankakee, Illinois, 60901

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • University Health Truman Medical Center

    Kansas City, Missouri, 64108

  • Cheshire Medical Center-Dartmouth-Hitchcock Keene

    Keene, New Hampshire, 03431

  • Aurora Cancer Care-Kenosha South

    Kenosha, Wisconsin, 53142

  • Kettering Medical Center

    Kettering, Ohio, 45429

  • Illinois CancerCare-Kewanee Clinic

    Kewanee, Illinois, 61443

  • ECU Health Oncology Kinston

    Kinston, North Carolina, 28501

  • Community Howard Regional Health

    Kokomo, Indiana, 46904

  • Gundersen Lutheran Medical Center

    La Crosse, Wisconsin, 54601

  • AMITA Health Adventist Medical Center

    La Grange, Illinois, 60525

  • IU Health La Porte Hospital

    La Porte, Indiana, 46350

  • LRGHealthcare-Lakes Region General Hospital

    Laconia, New Hampshire, 03246

  • IU Health Arnett Cancer Care

    Lafayette, Indiana, 47904

  • Saint Anthony Hospital

    Lakewood, Colorado, 80228

  • Saint Clare Hospital

    Lakewood, Washington, 98499

  • Fairfield Medical Center

    Lancaster, Ohio, 43130

  • Karmanos Cancer Institute at McLaren Greater Lansing

    Lansing, Michigan, 48910

  • University of Michigan Health - Sparrow Lansing

    Lansing, Michigan, 48912

  • Doctor's Hospital of Laredo

    Laredo, Texas, 78041

  • Kaiser Permanente - Largo Medical Center

    Largo, Maryland, 20774

  • Northside Hospital - Gwinnett

    Lawrenceville, Georgia, 30046

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

  • Beebe Medical Center

    Lewes, Delaware, 19958

  • Saint Rita's Medical Center

    Lima, Ohio, 45801

  • Nebraska Cancer Research Center

    Lincoln, Nebraska, 68510

  • AdventHealth Littleton

    Littleton, Colorado, 80122

  • Trinity Health Saint Mary Mercy Livonia Hospital

    Livonia, Michigan, 48154

  • Sky Ridge Medical Center

    Lone Tree, Colorado, 80124

  • Longmont United Hospital

    Longmont, Colorado, 80501

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Doctors Carrol, Sheth, Raghavan

    Louisville, Kentucky, 40215

  • Banner McKee Medical Center

    Loveland, Colorado, 80539

  • Lowell General Hospital

    Lowell, Massachusetts, 01854

  • Kaiser Permanente Lutherville - Timonium Medical Center

    Lutherville, Maryland, 21093

  • Illinois CancerCare-Macomb

    Macomb, Illinois, 61455

  • Mcdonough District Hospital

    Macomb, Illinois, 61455

  • Atrium Health Navicent

    Macon, Georgia, 31201

  • SSM Health Dean Medical Group - South Madison Campus

    Madison, Wisconsin, 53715

  • Solinsky Center for Cancer Care

    Manchester, New Hampshire, 03103

  • Holy Family Memorial Hospital

    Manitowoc, Wisconsin, 54221

  • Mayo Clinic Health Systems-Mankato

    Mankato, Minnesota, 56001

  • Wellstar Kennestone Hospital

    Marietta, Georgia, 30060

  • Marietta Memorial Hospital

    Marietta, Ohio, 45750

  • Aurora Bay Area Medical Group-Marinette

    Marinette, Wisconsin, 54143

  • Bay Area Medical Center

    Marinette, Wisconsin, 54143

  • UP Health System Marquette

    Marquette, Michigan, 49855

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • Marshfield Medical Center

    Marshfield, Wisconsin, 54449

  • Contra Costa Regional Medical Center

    Martinez, California, 94553-3156

  • Fremont - Rideout Cancer Center

    Marysville, California, 95901

  • Holy Family Hospital

    Methuen, Massachusetts, 01844

  • Mount Sinai Medical Center

    Miami Beach, Florida, 33140

  • Franciscan Saint Anthony Health-Michigan City

    Michigan City, Indiana, 46360

  • Middlesex Hospital

    Middletown, Connecticut, 06457

  • MyMichigan Medical Center Midland

    Midland, Michigan, 48670

  • Dana-Farber/Brigham and Women's Cancer Center at Milford Regional

    Milford, Massachusetts, 01757

  • Aurora Saint Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

Other trials in United States

Puerto Rico1 site

  • San Juan City Hospital

    San Juan, 00936

Other trials in Puerto Rico

About this study

Official title: Endocrine Therapy With or Without Anti-VEGF Therapy: A Randomized, Phase III Trial of Endocrine Therapy Alone or Endocrine Therapy Plus Bevacizumab (NSC 704865) for Women With Hormone Receptor-Positive Advanced Breast Cancer

This randomized phase III trial studies tamoxifen citrate or letrozole together with bevacizumab to see how well it works compared with tamoxifen citrate or letrozole alone in treating women with stage IIIB or stage IV breast cancer. Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen citrate or letrozole may fight breast cancer by blocking the use of estrogen by the tumor cells. Immunotherapy with monoclonal antibodies, such as bevacizumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving hormone therapy is more effective with or without bevacizumab in treating advanced breast cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To compare the progression-free survival of letrozole therapy alone with the combination of letrozole therapy plus bevacizumab as first-line treatment in women with estrogen- and/or progesterone-receptor-positive advanced breast cancer.

SECONDARY OBJECTIVES:

  1. To compare the proportion of patients receiving letrozole alone, who remain progression-free at 6 and 12 months, to those receiving letrozole plus bevacizumab.

II. To compare the incidence of objective response (complete response [CR] + partial response [PR]) in patients receiving letrozole with and without bevacizumab, as determined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, excluding patients with non-measurable disease.

III. To compare the incidence of clinical benefit (CR + PR + stable disease >= 6 months) in patients receiving letrozole with and without bevacizumab.

IV. To compare the duration of objective response in patients receiving letrozole with and without bevacizumab.

  1. To compare the time to treatment failure in patients receiving letrozole with and without bevacizumab.

VI. To compare the overall survival of patients receiving letrozole with and without bevacizumab, including the probability of survival until 36 months.

VII. To compare toxicity levels between the bevacizumab arm and the arm without bevacizumab in both the letrozole-treated patients and in the tamoxifen-treated patients.

VIII. To compare progression-free survival and overall survival of all patients receiving endocrine therapy with and without bevacizumab (by combining both letrozole and tamoxifen* patient subgroups).

CORRELATIVE OBJECTIVES:

  1. To compare baseline and changes in serial levels of circulating endothelial cells and circulating tumor cells in patients treated with endocrine therapy alone or endocrine therapy plus bevacizumab, and to explore the relationship of these markers with progression free survival.

II. To conduct proteomic analysis of longitudinal samples from patients with advanced-stage disease undergoing hormonal therapy to define new serum-based biomarkers related to disease activity.

III. To identify biologic correlates that will predict progression-free survival (PFS) and response to therapy.

IV. To conduct pharmacogenomic assessment of candidate variants in the VEGF, CYP2D6, and CYP19 genes and evaluate their association with PFS and other study outcomes.

  1. To identify single nucleotide polymorphisms (SNPs) associated with progression free survival in the genome-wide approach (GWAS).

VI. To identify factors other than chronological age that predict the risk of grade 3, 4 or 5 toxicity with bevacizumab and endocrine therapy by means of functional age assessment measures.

VII. To perform an exploratory analysis of the ability of the other factors included in the functional age assessment (either individual or in combination), to predict the risk of grade 3, 4 or 5 toxicity.

VIII. To evaluate longitudinal changes in the parameters of the factors described in objective VI while on therapy.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

NOTE: The placebo-controlled portion of the study was canceled on 5-15-10.

ARM I: Patients receive endocrine therapy* (tamoxifen citrate or letrozole) orally (PO) once daily (QD) on days 1-21 and bevacizumab intravenously (IV) over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive endocrine therapy* (tamoxifen citrate or letrozole) PO QD on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 6 months for the first 2 years and then annually for up to 3 years.

  • NOTE: As of 5/15/2011, patients only receive letrozole.
Being tested
Bevacizumab, Laboratory Biomarker Analysis, Letrozole, Questionnaire Administration, Tamoxifen Citrate
Medical subject headings
Breast Neoplasms

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

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • LetrozoleDrug

    Also called CGS 20267, CGS-20267, CGS20267, Femara

    Given PO

  • Questionnaire AdministrationOther

    Ancillary studies

  • Tamoxifen CitrateDrug

    Also called Apo-Tamox, Clonoxifen, Dignotamoxi, Ebefen

    Given PO

Study groups in NCT00601900
Study groupRoleWhat they receive
Arm I (endocrine therapy with monoclonal antibody)ExperimentalPatients receive endocrine therapy* (tamoxifen citrate* or letrozole) PO QD on days 1-21 and bevacizumab 15 mg/kg IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Bevacizumab; Other: Laboratory Biomarker Analysis; Drug: Letrozole; Other: Questionnaire Administration; Drug: Tamoxifen Citrate
Arm II (endocrine therapy)Active comparatorPatients receive endocrine therapy* (tamoxifen citrate* or letrozole) PO QD on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Drug: Letrozole; Other: Questionnaire Administration; Drug: Tamoxifen Citrate

What is being measured

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

  1. Progression-free Survival

    The Primary Endpoint for this study was to compare the progression-free survival of letrozole therapy alone with the combination of letrozole therapy plus bevacizumab as first-line treatment in women with estrogen- and/or progesterone-receptor-positive advanced breast cancer. Progression-free survival (PFS) was defined as the time from randomization until disease progression or death, whichever occurs first. The median PFS was estimated using the Kaplan-Meier method. Progression was assessed per RECIST criteria, and defined as at least a 20% increase in the sum of the longest diameters of target lesions from baseline or the appearance of new lesions.

    Measured: From randomization until disease progression or death whichever occurs first, assessed up to 5 years

Secondary outcomes (9)

  1. 12 Month Progression Free Survival Rate

    The 12 month progression-free survival rate was defined as the proportion of patients who were alive progression-free 12 months after registration into the study.

    Measured: At 12 months

  2. 6 Month Progression-Free Survival Rate

    The 6 month progression-free survival rate was defined as the proportion of patients who were alive progression-free 6 months after registration into the study.

    Measured: At 6 months

  3. Objective Response Rate

    Response was defined using RECIST criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions.

    Measured: Assessed up to 5 years

  4. Overall Survival (OS)

    OS is defined as the time from study entry to death from any cause. The median OS was estimated using the Kaplan-Meier method.

    Measured: Assessed up to 5 years

  5. Duration of Tumor Response

    Defined as the time from PR or CR, whichever comes first and by RECIST criteria, to progression or death.

    Measured: 5 years

  6. Overall Survival (OS) at 36 Months

    Proportion of patients surviving until 36 months

    Measured: 36 months

  7. Clinical Benefit Rate (CBR)

    To compare the rate of clinical benefit (CR + PR + stable disease ≥ 6 months) in patients receiving letrozole with and without bevacizumab.

    Measured: 5 years

  8. Time-to-treatment Failure

    From randomization until first disease progression, early termination of protocol therapy due to toxicity or withdrawn consent, or going onto non-protocol therapy. Defined by RECIST criteria. The proportional hazards model will be used to compare the arms on time-to-treatment-failure

    Measured: 5 years

  9. Grade 3 or Higher Treatment Related Toxicity

    Graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Events occuring in 5 percent or more of evaluable patients will be tabulated.

    Measured: 5 years

Timeline

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

  1. First posted28 Jan 2008 (estimated)
  2. Study start24 Sep 2008
  3. Primary completion30 Jun 2014
  4. Study completion29 Jan 2024

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
394 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00601900
Sponsor's protocol ID
NCI-2009-00477
Other IDs
NCI-2009-00477, CALGB-40503, CDR0000584091, CALGB 40503/CTSU 40503, CALGB-40503, CALGB-40503, U10CA180821, U10CA031946
Status last verified
Aug 2026
First submitted
18 Jan 2008
Last updated
28 Aug 2026
Data monitoring committee
No

Publications

  • Quintanilha JCF, Wang J, Sibley AB, Jiang C, Etheridge AS, Shen F, Jiang G, Mulkey F, Patel JN, Hertz DL, Dees EC, McLeod HL, Bertagnolli M, Rugo H, Kindler HL, Kelly WK, Ratain MJ, Kroetz DL, Owzar K, Schneider BP, Lin D, Innocenti F. Bevacizumab-induced hypertension and proteinuria: a genome-wide study of more than 1000 patients. Br J Cancer. 2022 Feb;126(2):265-274. doi: 10.1038/s41416-021-01557-w. Epub 2021 Oct 6.

    PubMed 34616010

  • Martin M, Loibl S, Hyslop T, De la Haba-Rodriguez J, Aktas B, Cirrincione CT, Mehta K, Barry WT, Morales S, Carey LA, Garcia-Saenz JA, Partridge A, Martinez-Janez N, Hahn O, Winer E, Guerrero-Zotano A, Hudis C, Casas M, Rodriguez-Martin C, Furlanetto J, Carrasco E, Dickler MN; GEICAM Spanish Breast Cancer Group; GBG (German Breast Group); Alliance for Clinical Trials in Oncology (Alliance). Evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for hormone receptor-positive metastatic breast cancer: a pooled analysis from the LEA (GEICAM/2006-11_GBG51) and CALGB 40503 (Alliance) trials. Eur J Cancer. 2019 Aug;117:91-98. doi: 10.1016/j.ejca.2019.06.002. Epub 2019 Jul 2.

    PubMed 31276981

  • Li D, McCall LM, Hahn OM, Hudis CA, Cohen HJ, Muss HB, Jatoi A, Lafky JM, Ballman KV, Winer EP, Tripathy D, Schneider B, Barry W, Dickler MN, Hurria A. Identification of risk factors for toxicity in patients with hormone receptor-positive advanced breast cancer treated with bevacizumab plus letrozole: a CALGB 40503 (alliance) correlative study. Breast Cancer Res Treat. 2018 Sep;171(2):325-334. doi: 10.1007/s10549-018-4828-5. Epub 2018 May 22.

    PubMed 29789969

  • Dickler MN, Barry WT, Cirrincione CT, Ellis MJ, Moynahan ME, Innocenti F, Hurria A, Rugo HS, Lake DE, Hahn O, Schneider BP, Tripathy D, Carey LA, Winer EP, Hudis CA. Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor-Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance). J Clin Oncol. 2016 Aug 1;34(22):2602-9. doi: 10.1200/JCO.2015.66.1595. Epub 2016 May 2.

    PubMed 27138575

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Bevacizumab, Laboratory Biomarker Analysis and Letrozole in people with Invasive Breast Carcinoma and Recurrent Breast Carcinoma, run by National Cancer Institute (NCI) at 522 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 62 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 522 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Aug 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (time frame: From randomization until disease progression or death whichever occurs first, assessed up to 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00601900, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2026.

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