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

April 3, 2024 updated by: National Cancer Institute (NCI)

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. 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:

I. 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.

V. 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:

I. 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.

V. 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.

Study Type

Interventional

Enrollment (Actual)

394

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 00936
        • San Juan City Hospital
  • United States
    • Alabama
      • Mobile, Alabama, United States, 36608
        • Providence Hospital
    • Arkansas
      • Fort Smith, Arkansas, United States, 72901
        • Sparks Regional Medical Center
    • California
      • Antioch, California, United States, 94531
        • East Bay Medical Oncology Hematology Medical Associates-Antioch
      • Berkeley, California, United States, 94704
        • Alta Bates Summit Medical Center-Herrick Campus
      • Burbank, California, United States, 91505
        • Providence Saint Joseph Medical Center/Disney Family Cancer Center
      • Burlingame, California, United States, 94010
        • Mills-Peninsula Medical Center
      • Castro Valley, California, United States, 94546
        • Eden Hospital Medical Center
      • Castro Valley, California, United States, 94546
        • East Bay Radiation Oncology Center
      • Castro Valley, California, United States, 94546
        • Valley Medical Oncology Consultants-Castro Valley
      • Chico, California, United States, 95973
        • Adventist Health Cancer Care Center Chico
      • Clovis, California, United States, 93611
        • Community Cancer Institute
      • Emeryville, California, United States, 94608
        • Bay Area Breast Surgeons Inc
      • Fremont, California, United States, 94538
        • Valley Medical Oncology Consultants-Fremont
      • Greenbrae, California, United States, 94904
        • Marin General Hospital
      • Los Angeles, California, United States, 90033
        • USC / Norris Comprehensive Cancer Center
      • Los Angeles, California, United States, 90033
        • Los Angeles General Medical Center
      • Martinez, California, United States, 94553-3156
        • Contra Costa Regional Medical Center
      • Marysville, California, United States, 95901
        • Fremont - Rideout Cancer Center
      • Modesto, California, United States, 95355
        • Memorial Medical Center
      • Mountain View, California, United States, 94040
        • El Camino Hospital
      • Novato, California, United States, 94945
        • Sutter Cancer Research Consortium
      • Oakland, California, United States, 94609
        • Alta Bates Summit Medical Center - Summit Campus
      • Oakland, California, United States, 94609
        • Hematology and Oncology Associates-Oakland
      • Oakland, California, United States, 94602
        • Highland General Hospital
      • Oakland, California, United States, 94609
        • Tom K Lee Inc
      • Oakland, California, United States, 94609
        • Bay Area Tumor Institute
      • Orange, California, United States, 92868
        • UC Irvine Health/Chao Family Comprehensive Cancer Center
      • Pleasant Hill, California, United States, 94523
        • East Bay Medical Oncology Hematology Medical Associates Inc-Pleasant Hill
      • Pleasant Hill, California, United States, 94523
        • John Muir Health Cancer Medical Group
      • Pleasanton, California, United States, 94588
        • Valley Care Health System - Pleasanton
      • Pleasanton, California, United States, 94588
        • Valley Medical Oncology Consultants
      • Pomona, California, United States, 91767
        • Pomona Valley Hospital Medical Center
      • Sacramento, California, United States, 95817
        • University of California Davis Comprehensive Cancer Center
      • Saint Helena, California, United States, 94574
        • Saint Helena Hospital
      • San Francisco, California, United States, 94115
        • California Pacific Medical Center-Pacific Campus
      • San Francisco, California, United States, 94115
        • UCSF Medical Center-Mount Zion
      • San Francisco, California, United States, 94110
        • Zuckerberg San Francisco General Hospital
      • San Leandro, California, United States, 94578
        • East Bay Medical Oncology Hematology Associates Inc
      • San Pablo, California, United States, 94806
        • Doctors Medical Center- JC Robinson Regional Cancer Center
      • Truckee, California, United States, 96161
        • Gene Upshaw Memorial Tahoe Forest Cancer Center
      • Vacaville, California, United States, 95687
        • Northbay Cancer Center
      • Vallejo, California, United States, 94589
        • Sutter Solano Medical Center/Cancer Center
    • Colorado
      • Aurora, Colorado, United States, 80012
        • The Medical Center of Aurora
      • Boulder, Colorado, United States, 80301
        • Boulder Community Hospital
      • Colorado Springs, Colorado, United States, 80907
        • Penrose-Saint Francis Healthcare
      • Denver, Colorado, United States, 80210
        • Porter Adventist Hospital
      • Denver, Colorado, United States, 80218
        • Presbyterian - Saint Lukes Medical Center - Health One
      • Denver, Colorado, United States, 80218
        • SCL Health Saint Joseph Hospital
      • Denver, Colorado, United States, 80220
        • Rose Medical Center
      • Denver, Colorado, United States, 80222
        • Western States Cancer Research NCORP
      • Englewood, Colorado, United States, 80113
        • Swedish Medical Center
      • Fort Collins, Colorado, United States, 80524
        • Poudre Valley Hospital
      • Grand Junction, Colorado, United States, 81501
        • Saint Mary's Hospital and Regional Medical Center
      • Greeley, Colorado, United States, 80631
        • North Colorado Medical Center
      • Lakewood, Colorado, United States, 80228
        • Saint Anthony Hospital
      • Littleton, Colorado, United States, 80122
        • Littleton Adventist Hospital
      • Lone Tree, Colorado, United States, 80124
        • Sky Ridge Medical Center
      • Longmont, Colorado, United States, 80501
        • Longmont United Hospital
      • Loveland, Colorado, United States, 80539
        • McKee Medical Center
      • Pueblo, Colorado, United States, 81004
        • Saint Mary Corwin Medical Center
      • Thornton, Colorado, United States, 80229
        • North Suburban Medical Center
      • Wheat Ridge, Colorado, United States, 80033
        • SCL Health Lutheran Medical Center
    • Connecticut
      • Hartford, Connecticut, United States, 06105
        • Smilow Cancer Hospital Care Center at Saint Francis
      • Hartford, Connecticut, United States, 06102
        • Hartford Hospital
      • Middletown, Connecticut, United States, 06457
        • Middlesex Hospital
      • New Britain, Connecticut, United States, 06050
        • The Hospital of Central Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale University
      • Stamford, Connecticut, United States, 06904
        • Stamford Hospital/Bennett Cancer Center
    • Delaware
      • Lewes, Delaware, United States, 19958
        • Beebe Medical Center
      • Newark, Delaware, United States, 19718
        • Christiana Care Health System-Christiana Hospital
    • District of Columbia
      • Washington, District of Columbia, United States, 20016
        • Sibley Memorial Hospital
    • Florida
      • Boca Raton, Florida, United States, 33486
        • Boca Raton Regional Hospital
      • Fort Lauderdale, Florida, United States, 33308
        • Holy Cross Hospital
      • Gainesville, Florida, United States, 32605
        • Florida Cancer Specialists-Gainesville Cancer Center
      • Jupiter, Florida, United States, 33458
        • Jupiter Medical Center
      • Miami Beach, Florida, United States, 33140
        • Mount Sinai Medical Center
    • Georgia
      • Athens, Georgia, United States, 30607
        • University Cancer and Blood Center LLC
      • Atlanta, Georgia, United States, 30342
        • Emory Saint Joseph's Hospital
      • Atlanta, Georgia, United States, 30309
        • Piedmont Hospital
      • Atlanta, Georgia, United States, 30342
        • Northside Hospital
      • Atlanta, Georgia, United States, 30342
        • Atlanta Regional CCOP
      • Augusta, Georgia, United States, 30912
        • Augusta University Medical Center
      • Austell, Georgia, United States, 30106
        • WellStar Cobb Hospital
      • Columbus, Georgia, United States, 31904
        • John B Amos Cancer Center
      • Decatur, Georgia, United States, 30033
        • Dekalb Medical Center
      • Dublin, Georgia, United States, 31021
        • Dublin Hematology Oncology Care PC
      • Fayetteville, Georgia, United States, 30214
        • Piedmont Fayette Hospital
      • Fort Gordon, Georgia, United States, 30905-5650
        • Eisenhower Army Medical Center
      • Gainesville, Georgia, United States, 30501
        • Northeast Georgia Medical Center-Gainesville
      • Lawrenceville, Georgia, United States, 30046
        • Northside Hospital - Gwinnett
      • Macon, Georgia, United States, 31201
        • Medical Center of Central Georgia
      • Marietta, Georgia, United States, 30060
        • WellStar Kennestone Hospital
      • Riverdale, Georgia, United States, 30274
        • Southern Regional Medical Center
      • Rome, Georgia, United States, 30165
        • Harbin Clinic Medical Oncology and Clinical Research
    • Hawaii
      • 'Aiea, Hawaii, United States, 96701
        • Pali Momi Medical Center
      • Honolulu, Hawaii, United States, 96813
        • Queen's Medical Center
      • Honolulu, Hawaii, United States, 96817
        • The Cancer Center of Hawaii-Liliha
      • Honolulu, Hawaii, United States, 96813
        • Hawaii Cancer Care Inc - Waterfront Plaza
      • Honolulu, Hawaii, United States, 96813
        • Straub Clinic and Hospital
      • Honolulu, Hawaii, United States, 96813
        • University of Hawaii Cancer Center
      • Honolulu, Hawaii, United States, 96817
        • Queen's Cancer Center - Kuakini
      • Honolulu, Hawaii, United States, 96826
        • Kapiolani Medical Center for Women and Children
      • Wailuku, Hawaii, United States, 96793
        • Maui Memorial Medical Center
      • Wailuku, Hawaii, United States, 96793
        • Pacific Cancer Institute of Maui
    • Illinois
      • Alton, Illinois, United States, 62002
        • Saint Anthony's Health
      • Aurora, Illinois, United States, 60504
        • Rush - Copley Medical Center
      • Bloomington, Illinois, United States, 61704
        • Illinois CancerCare-Bloomington
      • Bloomington, Illinois, United States, 61701
        • Saint Joseph Medical Center
      • Canton, Illinois, United States, 61520
        • Illinois CancerCare-Canton
      • Canton, Illinois, United States, 61520
        • Graham Hospital Association
      • Carthage, Illinois, United States, 62321
        • Illinois CancerCare-Carthage
      • Carthage, Illinois, United States, 62321
        • Memorial Hospital
      • Chicago, Illinois, United States, 60637
        • University of Chicago Comprehensive Cancer Center
      • Chicago, Illinois, United States, 60612
        • John H Stroger Jr Hospital of Cook County
      • Chicago, Illinois, United States, 60608
        • Mount Sinai Hospital Medical Center
      • Chicago, Illinois, United States, 60631
        • Presence Resurrection Medical Center
      • Chicago, Illinois, United States, 60657
        • Advocate Illinois Masonic Medical Center
      • Chicago, Illinois, United States, 60616
        • Mercy Hospital and Medical Center
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital
      • Decatur, Illinois, United States, 62526
        • Heartland Cancer Research NCORP
      • Downers Grove, Illinois, United States, 60515
        • Advocate Good Samaritan Hospital
      • Elk Grove Village, Illinois, United States, 60007
        • Ascension Alexian Brothers - Elk Grove Village
      • Elmhurst, Illinois, United States, 60126
        • Elmhurst Memorial Hospital
      • Eureka, Illinois, United States, 61530
        • Illinois CancerCare-Eureka
      • Eureka, Illinois, United States, 61530
        • Eureka Hospital
      • Freeport, Illinois, United States, 61032
        • Freeport Memorial Hospital/Leonard C Ferguson Cancer Center
      • Galesburg, Illinois, United States, 61401
        • Illinois CancerCare-Galesburg
      • Harvey, Illinois, United States, 60426
        • Ingalls Memorial Hospital
      • Havana, Illinois, United States, 62644
        • Mason District Hospital
      • Havana, Illinois, United States, 62644
        • Illinois CancerCare-Havana
      • Joliet, Illinois, United States, 60435
        • Duly Health and Care Joliet
      • Kankakee, Illinois, United States, 60901
        • Presence Saint Mary's Hospital
      • Kewanee, Illinois, United States, 61443
        • Illinois CancerCare-Kewanee Clinic
      • La Grange, Illinois, United States, 60525
        • AMITA Health Adventist Medical Center
      • Macomb, Illinois, United States, 61455
        • Illinois CancerCare-Macomb
      • Macomb, Illinois, United States, 61455
        • Mcdonough District Hospital
      • Moline, Illinois, United States, 61265
        • Garneau, Stewart C MD (UIA Investigator)
      • Moline, Illinois, United States, 61265
        • Porubcin, Michael MD (UIA Investigator)
      • Moline, Illinois, United States, 61265
        • Spector, David MD (UIA Investigator)
      • Moline, Illinois, United States, 61265
        • Trinity Medical Center
      • Moline, Illinois, United States, 61265
        • Sharis, Christine M MD (UIA Investigator)
      • Moline, Illinois, United States, 61265
        • Stoffel, Thomas J MD (UIA Investigator)
      • Monmouth, Illinois, United States, 61462
        • Illinois CancerCare-Monmouth
      • Monmouth, Illinois, United States, 61462
        • Holy Family Medical Center
      • Mount Vernon, Illinois, United States, 62864
        • Good Samaritan Regional Health Center
      • Normal, Illinois, United States, 61761
        • Carle Cancer Institute Normal
      • Normal, Illinois, United States, 61761
        • Bromenn Regional Medical Center
      • Normal, Illinois, United States, 61761
        • Illinois CancerCare-Community Cancer Center
      • Ottawa, Illinois, United States, 61350
        • Illinois CancerCare-Ottawa Clinic
      • Ottawa, Illinois, United States, 61350
        • Ottawa Regional Hospital and Healthcare Center
      • Pekin, Illinois, United States, 61554
        • Illinois CancerCare-Pekin
      • Pekin, Illinois, United States, 61554
        • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
      • Peoria, Illinois, United States, 61636
        • Methodist Medical Center of Illinois
      • Peoria, Illinois, United States, 61637
        • OSF Saint Francis Medical Center
      • Peoria, Illinois, United States, 61615
        • Illinois CancerCare-Peoria
      • Peoria, Illinois, United States, 61614
        • Proctor Hospital
      • Peru, Illinois, United States, 61354
        • Illinois CancerCare-Peru
      • Peru, Illinois, United States, 61354
        • Illinois Valley Hospital
      • Princeton, Illinois, United States, 61356
        • Illinois CancerCare-Princeton
      • Princeton, Illinois, United States, 61356
        • Perry Memorial Hospital
      • Spring Valley, Illinois, United States, 61362
        • Illinois CancerCare-Spring Valley
      • Springfield, Illinois, United States, 62781
        • Memorial Medical Center
      • Urbana, Illinois, United States, 61801
        • Carle Cancer Center
    • Indiana
      • Beech Grove, Indiana, United States, 46107
        • Franciscan Saint Francis Health-Beech Grove
      • Elkhart, Indiana, United States, 46515
        • Elkhart General Hospital
      • Elkhart, Indiana, United States, 46514
        • Michiana Hematology Oncology PC-Elkhart
      • Elkhart, Indiana, United States, 46514-2098
        • Elkhart Clinic
      • Fort Wayne, Indiana, United States, 46845
        • Fort Wayne Medical Oncology and Hematology Inc-Parkview
      • Indianapolis, Indiana, United States, 46260
        • Ascension Saint Vincent Indianapolis Hospital
      • Kokomo, Indiana, United States, 46904
        • Community Howard Regional Health
      • La Porte, Indiana, United States, 46350
        • IU Health La Porte Hospital
      • Lafayette, Indiana, United States, 47904
        • IU Health Arnett Cancer Care
      • Michigan City, Indiana, United States, 46360
        • Franciscan Saint Anthony Health-Michigan City
      • Mishawaka, Indiana, United States, 46545
        • Michiana Hematology Oncology PC-Mishawaka
      • Mishawaka, Indiana, United States, 46545
        • Saint Joseph Regional Medical Center-Mishawaka
      • Plymouth, Indiana, United States, 46563
        • Michiana Hematology Oncology PC-Plymouth
      • Richmond, Indiana, United States, 47374
        • Reid Health
      • South Bend, Indiana, United States, 46601
        • Memorial Hospital of South Bend
      • South Bend, Indiana, United States, 46601
        • Michiana Hematology Oncology PC-South Bend
      • South Bend, Indiana, United States, 46628
        • Northern Indiana Cancer Research Consortium
      • Westville, Indiana, United States, 46391
        • Michiana Hematology Oncology PC-Westville
    • Iowa
      • Ames, Iowa, United States, 50010
        • McFarland Clinic - Ames
      • Bettendorf, Iowa, United States, 52722
        • Constantinou, Costas L MD (UIA Investigator)
      • Bettendorf, Iowa, United States, 52722
        • University of Iowa Healthcare Cancer Services Quad Cities
      • Clive, Iowa, United States, 50325
        • Medical Oncology and Hematology Associates-West Des Moines
      • Des Moines, Iowa, United States, 50309
        • Iowa Methodist Medical Center
      • Des Moines, Iowa, United States, 50314
        • Mercy Medical Center - Des Moines
      • Des Moines, Iowa, United States, 50309
        • Medical Oncology and Hematology Associates-Des Moines
      • Des Moines, Iowa, United States, 50314
        • Mission Cancer and Blood - Laurel
      • Des Moines, Iowa, United States, 50316
        • Iowa Lutheran Hospital
      • Des Moines, Iowa, United States, 50309
        • Iowa-Wide Oncology Research Coalition NCORP
      • Des Moines, Iowa, United States, 50307
        • Mercy Capitol
      • Iowa City, Iowa, United States, 52242
        • University of Iowa/Holden Comprehensive Cancer Center
      • Ottumwa, Iowa, United States, 52501
        • Ottumwa Regional Health Center
      • Sioux City, Iowa, United States, 51101
        • Siouxland Regional Cancer Center
      • Sioux City, Iowa, United States, 51102
        • Mercy Medical Center-Sioux City
      • Sioux City, Iowa, United States, 51104
        • Saint Luke's Regional Medical Center
    • Kansas
      • Hays, Kansas, United States, 67601
        • HaysMed University of Kansas Health System
      • Hutchinson, Kansas, United States, 67502
        • Hutchinson Regional Medical Center
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Cancer Center
      • Olathe, Kansas, United States, 66061
        • Olathe Cancer Center
      • Pittsburg, Kansas, United States, 66762
        • Ascension Via Christi - Pittsburg
      • Salina, Kansas, United States, 67401
        • Salina Regional Health Center
      • Topeka, Kansas, United States, 66606
        • University of Kansas Health System Saint Francis Campus
      • Topeka, Kansas, United States, 66606
        • Cotton O'Neil Cancer Center / Stormont Vail Health
    • Kentucky
      • Ashland, Kentucky, United States, 41101
        • Our Lady Bellefonte Hospital
      • Louisville, Kentucky, United States, 40215
        • Doctors Carrol, Sheth, Raghavan
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70809
        • Mary Bird Perkins Cancer Center
      • Baton Rouge, Louisiana, United States, 70809
        • Ochsner Health Center-Summa
      • Baton Rouge, Louisiana, United States, 70809
        • Hematology/Oncology Clinic PLLC
      • Covington, Louisiana, United States, 70433
        • Ochsner Health Center-Covington
      • New Orleans, Louisiana, United States, 70112
        • Tulane University School of Medicine
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Medical Center Jefferson
      • New Orleans, Louisiana, United States, 70112
        • Louisiana State University Health Science Center
      • New Orleans, Louisiana, United States, 70115
        • Ochsner Baptist Medical Center
    • Maine
      • Augusta, Maine, United States, 04330
        • Harold Alfond Center for Cancer Care
      • Bangor, Maine, United States, 04401
        • Eastern Maine Medical Center
      • Scarborough, Maine, United States, 04074
        • Maine Center for Cancer Medicine-Scarborough
    • Maryland
      • Baltimore, Maryland, United States, 21215
        • Sinai Hospital of Baltimore
      • Baltimore, Maryland, United States, 21204
        • Greater Baltimore Medical Center
      • Baltimore, Maryland, United States, 21201
        • University of Maryland/Greenebaum Cancer Center
      • Baltimore, Maryland, United States, 21201
        • Veterans Administration Medical Center-Baltimore
      • Elkton, Maryland, United States, 21921
        • Christiana Care - Union Hospital
      • Frederick, Maryland, United States, 21701
        • Frederick Memorial Hospital
      • Hagerstown, Maryland, United States, 21742
        • Meritus Medical Center
      • Largo, Maryland, United States, 20774
        • Kaiser Permanente - Largo Medical Center
      • Lutherville, Maryland, United States, 21093
        • Kaiser Permanente Lutherville - Timonium Medical Center
      • Rockville, Maryland, United States, 20850
        • Kaiser Permanente - Shady Grove Medical Center
      • Silver Spring, Maryland, United States, 20910
        • Holy Cross Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Gloucester, Massachusetts, United States, 01930
        • Addison Gilbert Hospital
      • Hyannis, Massachusetts, United States, 02601
        • Cape Cod Hospital
      • Lowell, Massachusetts, United States, 01854
        • Lowell General Hospital
      • Methuen, Massachusetts, United States, 01844
        • Holy Family Hospital
      • Milford, Massachusetts, United States, 01757
        • Dana-Farber/Brigham and Women's Cancer Center at Milford Regional
      • Newton, Massachusetts, United States, 02462
        • Newton-Wellesley Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • Saint Joseph Mercy Hospital
      • Ann Arbor, Michigan, United States, 48106
        • Michigan Cancer Research Consortium NCORP
      • Battle Creek, Michigan, United States, 49017
        • Bronson Battle Creek
      • Bay City, Michigan, United States, 48706
        • McLaren Cancer Institute-Bay City
      • Big Rapids, Michigan, United States, 49307
        • Spectrum Health Big Rapids Hospital
      • Dearborn, Michigan, United States, 48124
        • Beaumont Hospital - Dearborn
      • Detroit, Michigan, United States, 48201
        • Wayne State University/Karmanos Cancer Institute
      • Detroit, Michigan, United States, 48236
        • Ascension Saint John Hospital
      • East Lansing, Michigan, United States, 48824
        • Michigan State University Clinical Center
      • Escanaba, Michigan, United States, 49829
        • Green Bay Oncology - Escanaba
      • Flint, Michigan, United States, 48532
        • Genesys Regional Medical Center-West Flint Campus
      • Flint, Michigan, United States, 48532
        • McLaren Cancer Institute-Flint
      • Flint, Michigan, United States, 48503
        • Hurley Medical Center
      • Grand Rapids, Michigan, United States, 49503
        • Spectrum Health at Butterworth Campus
      • Grand Rapids, Michigan, United States, 49503
        • Cancer Research Consortium of West Michigan NCORP
      • Grand Rapids, Michigan, United States, 49503
        • Trinity Health Grand Rapids Hospital
      • Iron Mountain, Michigan, United States, 49801
        • Green Bay Oncology - Iron Mountain
      • Jackson, Michigan, United States, 49201
        • Allegiance Health
      • Kalamazoo, Michigan, United States, 49007
        • West Michigan Cancer Center
      • Kalamazoo, Michigan, United States, 49007
        • Bronson Methodist Hospital
      • Kalamazoo, Michigan, United States, 49048
        • Borgess Medical Center
      • Lansing, Michigan, United States, 48910
        • Karmanos Cancer Institute at McLaren Greater Lansing
      • Lansing, Michigan, United States, 48912
        • University of Michigan Health - Sparrow Lansing
      • Livonia, Michigan, United States, 48154
        • Trinity Health Saint Mary Mercy Livonia Hospital
      • Marquette, Michigan, United States, 49855
        • UP Health System Marquette
      • Midland, Michigan, United States, 48670
        • MyMichigan Medical Center Midland
      • Muskegon, Michigan, United States, 49442
        • Mercy Health Partners-Hackley Campus
      • Muskegon, Michigan, United States, 49444
        • Trinity Health Muskegon Hospital
      • Niles, Michigan, United States, 49120
        • Corewell Health Lakeland Hospitals - Niles Hospital
      • Petoskey, Michigan, United States, 49770
        • McLaren Cancer Institute-Northern Michigan
      • Pontiac, Michigan, United States, 48341
        • Saint Joseph Mercy Oakland
      • Port Huron, Michigan, United States, 48060
        • Lake Huron Medical Center
      • Saginaw, Michigan, United States, 48601
        • Ascension Saint Mary's Hospital
      • Saint Joseph, Michigan, United States, 49085
        • Lakeland Medical Center Saint Joseph
      • Saint Joseph, Michigan, United States, 49085
        • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
      • Southfield, Michigan, United States, 48075
        • Ascension Providence Hospitals - Southfield
      • Traverse City, Michigan, United States, 49684
        • Munson Medical Center
      • Warren, Michigan, United States, 48093
        • Saint John Macomb-Oakland Hospital
      • Wyoming, Michigan, United States, 49519
        • University of Michigan Health - West
    • Minnesota
      • Alexandria, Minnesota, United States, 56308
        • Medini, Eitan MD (UIA Investigator)
      • Duluth, Minnesota, United States, 55805
        • Essentia Health Cancer Center
      • Duluth, Minnesota, United States, 55805
        • Essentia Health Saint Mary's Medical Center
      • Duluth, Minnesota, United States, 55805
        • Miller-Dwan Hospital
      • Fergus Falls, Minnesota, United States, 56537
        • Etzell, Paul S MD (UIA Investigator)
      • Fergus Falls, Minnesota, United States, 56537
        • Swenson, Wade II, MD (UIA Investigator)
      • Mankato, Minnesota, United States, 56001
        • Mayo Clinic Health Systems-Mankato
      • Saint Cloud, Minnesota, United States, 56303
        • Coborn Cancer Center at Saint Cloud Hospital
      • Saint Cloud, Minnesota, United States, 56303
        • Saint Cloud Hospital
      • Willmar, Minnesota, United States, 56201
        • Rice Memorial Hospital
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
      • Pascagoula, Mississippi, United States, 39581
        • Singing River Hospital
    • Missouri
      • Bolivar, Missouri, United States, 65613
        • Central Care Cancer Center - Bolivar
      • Branson, Missouri, United States, 65616
        • Cox Cancer Center Branson
      • Cape Girardeau, Missouri, United States, 63703
        • Saint Francis Medical Center
      • Cape Girardeau, Missouri, United States, 63703
        • Southeast Cancer Center
      • Cape Girardeau, Missouri, United States, 63701
        • Southeast Missouri Hospital
      • Columbia, Missouri, United States, 65212
        • MU Health - University Hospital/Ellis Fischel Cancer Center
      • Jefferson City, Missouri, United States, 65109
        • Capital Region Southwest Campus
      • Joplin, Missouri, United States, 64804
        • Freeman Health System
      • Kansas City, Missouri, United States, 64108
        • Truman Medical Centers
      • Rolla, Missouri, United States, 65401
        • Delbert Day Cancer Institute at PCRMC
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • Saint Louis, Missouri, United States, 63131
        • Missouri Baptist Medical Center
      • Saint Louis, Missouri, United States, 63141
        • Mercy Hospital Saint Louis
      • Saint Louis, Missouri, United States, 63109
        • Saint Louis Cancer and Breast Institute-South City
      • Saint Louis, Missouri, United States, 63141
        • Saint Louis-Cape Girardeau CCOP
      • Saint Louis, Missouri, United States, 63141
        • Comprehensive Cancer Care PC
      • Springfield, Missouri, United States, 65804
        • Cancer Research for the Ozarks NCORP
      • Springfield, Missouri, United States, 65807
        • CoxHealth South Hospital
      • Springfield, Missouri, United States, 65804
        • Mercy Hospital Springfield
    • Montana
      • Billings, Montana, United States, 59101
        • Billings Clinic Cancer Center
      • Billings, Montana, United States, 59101
        • Saint Vincent Healthcare
      • Billings, Montana, United States, 59102
        • Montana Cancer Consortium NCORP
      • Billings, Montana, United States, 59101
        • Northern Rockies Radiation Oncology Center
      • Billings, Montana, United States, 59102
        • Saint Vincent Frontier Cancer Center
      • Bozeman, Montana, United States, 59715
        • Bozeman Deaconess Hospital
      • Butte, Montana, United States, 59701
        • Saint James Community Hospital and Cancer Treatment Center
      • Great Falls, Montana, United States, 59405
        • Great Falls Clinic
      • Great Falls, Montana, United States, 59405
        • Benefis Healthcare- Sletten Cancer Institute
      • Great Falls, Montana, United States, 59405
        • Berdeaux, Donald MD (UIA Investigator)
      • Havre, Montana, United States, 59501
        • Northern Montana Hospital
      • Helena, Montana, United States, 59601
        • Saint Peter's Community Hospital
      • Kalispell, Montana, United States, 59901
        • Kalispell Regional Medical Center
      • Kalispell, Montana, United States, 59901
        • Glacier Oncology PLLC
      • Kalispell, Montana, United States, 59901
        • Kalispell Medical Oncology
      • Missoula, Montana, United States, 59804
        • Community Medical Hospital
      • Missoula, Montana, United States, 59802
        • Saint Patrick Hospital - Community Hospital
      • Missoula, Montana, United States, 59804
        • Guardian Oncology and Center for Wellness
      • Missoula, Montana, United States, 59802
        • Montana Cancer Specialists
    • Nebraska
      • Grand Island, Nebraska, United States, 68803
        • CHI Health Saint Francis
      • Lincoln, Nebraska, United States, 68510
        • Nebraska Cancer Research Center
      • North Platte, Nebraska, United States, 69101
        • Great Plains Health Callahan Cancer Center
      • Omaha, Nebraska, United States, 68198
        • University Of Nebraska Medical Center
      • Omaha, Nebraska, United States, 68124
        • Alegent Health Bergan Mercy Medical Center
      • Omaha, Nebraska, United States, 68122
        • Alegent Health Immanuel Medical Center
      • Omaha, Nebraska, United States, 68131
        • Creighton University Medical Center
      • Omaha, Nebraska, United States, 68106
        • Missouri Valley Cancer Consortium
    • Nevada
      • Reno, Nevada, United States, 89502
        • Renown Regional Medical Center
    • New Hampshire
      • Concord, New Hampshire, United States, 03301
        • New Hampshire Oncology Hematology PA-Concord
      • Keene, New Hampshire, United States, 03431
        • Cheshire Medical Center-Dartmouth-Hitchcock Keene
      • Laconia, New Hampshire, United States, 03246
        • LRGHealthcare-Lakes Region General Hospital
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
      • Manchester, New Hampshire, United States, 03103
        • Solinsky Center for Cancer Care
      • Nashua, New Hampshire, United States, 03060
        • Saint Joseph Hospital
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • Cooper Hospital University Medical Center
      • Freehold, New Jersey, United States, 07728
        • CentraState Medical Center
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
      • Morristown, New Jersey, United States, 07960
        • Morristown Medical Center
      • Newark, New Jersey, United States, 07112
        • Newark Beth Israel Medical Center
      • Summit, New Jersey, United States, 07902
        • Overlook Hospital
      • Vineland, New Jersey, United States, 08360
        • Inspira Medical Center Vineland
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center - Moses Campus
      • Bronx, New York, United States, 10461
        • Montefiore Medical Center-Weiler Hospital
      • Bronx, New York, United States, 10466
        • Montefiore Medical Center-Wakefield Campus
      • East Syracuse, New York, United States, 13057
        • Hematology Oncology Associates of Central New York-East Syracuse
      • Elmhurst, New York, United States, 11373
        • Elmhurst Hospital Center
      • Elmira, New York, United States, 14905
        • Arnot Ogden Medical Center/Falck Cancer Center
      • Glens Falls, New York, United States, 12801
        • Adirondack Cancer Center
      • Jamaica, New York, United States, 11432
        • Queens Hospital Center
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10019
        • Mount Sinai West
      • New York, New York, United States, 10032
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
      • New York, New York, United States, 10065
        • NYP/Weill Cornell Medical Center
      • New York, New York, United States, 10035
        • Ralph Lauren Center for Cancer Care and Prevention
      • New York, New York, United States, 10003
        • Mount Sinai Union Square
      • Rochester, New York, United States, 14642
        • University of Rochester
      • Rochester, New York, United States, 14620
        • Highland Hospital
      • Rochester, New York, United States, 14623
        • Interlakes Foundation Inc-Rochester
      • Staten Island, New York, United States, 10305
        • Staten Island University Hospital
      • Utica, New York, United States, 13502
        • Faxton-Saint Luke's Healthcare
    • North Carolina
      • Asheboro, North Carolina, United States, 27203
        • Randolph Hospital
      • Chapel Hill, North Carolina, United States, 27599
        • UNC Lineberger Comprehensive Cancer Center
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Medical Center/Levine Cancer Institute
      • Goldsboro, North Carolina, United States, 27534
        • Wayne Memorial Hospital
      • Greensboro, North Carolina, United States, 27403
        • Cone Health Cancer Center
      • Kinston, North Carolina, United States, 28501
        • Vidant Oncology-Kinston
      • Reidsville, North Carolina, United States, 27320
        • Annie Penn Memorial Hospital
      • Rutherfordton, North Carolina, United States, 28139
        • Rutherford Hospital
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
      • Winston-Salem, North Carolina, United States, 27104
        • Southeast Clinical Oncology Research Consortium NCORP
    • North Dakota
      • Bismarck, North Dakota, United States, 58501
        • Sanford Bismarck Medical Center
      • Bismarck, North Dakota, United States, 58501
        • Mid Dakota Clinic
      • Bismarck, North Dakota, United States, 58501
        • Saint Alexius Medical Center
      • Grand Forks, North Dakota, United States, 58201
        • Altru Cancer Center
      • Minot, North Dakota, United States, 58701
        • Trinity Cancer Care Center
    • Ohio
      • Bellefontaine, Ohio, United States, 43311
        • Mary Rutan Hospital
      • Canton, Ohio, United States, 44710
        • Aultman Health Foundation
      • Chillicothe, Ohio, United States, 45601
        • Adena Regional Medical Center
      • Cleveland, Ohio, United States, 44109
        • MetroHealth Medical Center
      • Columbus, Ohio, United States, 43214
        • Riverside Methodist Hospital
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center
      • Columbus, Ohio, United States, 43228
        • Doctors Hospital
      • Columbus, Ohio, United States, 43215
        • Grant Medical Center
      • Columbus, Ohio, United States, 43222
        • Mount Carmel Health Center West
      • Columbus, Ohio, United States, 43215
        • Columbus NCI Community Oncology Research Program
      • Dayton, Ohio, United States, 45406
        • Good Samaritan Hospital - Dayton
      • Dayton, Ohio, United States, 45409
        • Miami Valley Hospital
      • Dayton, Ohio, United States, 45415
        • Miami Valley Hospital North
      • Dayton, Ohio, United States, 45405
        • Grandview Hospital
      • Dayton, Ohio, United States, 45428
        • Dayton Veterans Affairs Medical Center
      • Delaware, Ohio, United States, 43015
        • Grady Memorial Hospital
      • Findlay, Ohio, United States, 45840
        • Blanchard Valley Hospital
      • Franklin, Ohio, United States, 45005-1066
        • Atrium Medical Center-Middletown Regional Hospital
      • Greenville, Ohio, United States, 45331
        • Wayne Hospital
      • Kettering, Ohio, United States, 45429
        • Kettering Medical Center
      • Lancaster, Ohio, United States, 43130
        • Fairfield Medical Center
      • Lima, Ohio, United States, 45801
        • Saint Rita's Medical Center
      • Marietta, Ohio, United States, 45750
        • Marietta Memorial Hospital
      • Mount Vernon, Ohio, United States, 43050
        • Knox Community Hospital
      • Newark, Ohio, United States, 43055
        • Licking Memorial Hospital
      • Portsmouth, Ohio, United States, 45662
        • Southern Ohio Medical Center
      • Springfield, Ohio, United States, 45505
        • Springfield Regional Medical Center
      • Troy, Ohio, United States, 45373
        • Upper Valley Medical Center
      • Westerville, Ohio, United States, 43081
        • Saint Ann's Hospital
      • Wilmington, Ohio, United States, 45177
        • Clinton Memorial Hospital
      • Xenia, Ohio, United States, 45385
        • Greene Memorial Hospital
      • Zanesville, Ohio, United States, 43701
        • Genesis Healthcare System Cancer Care Center
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74136
        • Natalie Warren Bryant Cancer Center at Saint Francis
    • Oregon
      • Bend, Oregon, United States, 97701
        • Saint Charles Health System
      • Clackamas, Oregon, United States, 97015
        • Clackamas Radiation Oncology Center
      • Gresham, Oregon, United States, 97030
        • Legacy Mount Hood Medical Center
      • Milwaukie, Oregon, United States, 97222
        • Providence Milwaukie Hospital
      • Newberg, Oregon, United States, 97132
        • Providence Newberg Medical Center
      • Oregon City, Oregon, United States, 97045
        • Providence Willamette Falls Medical Center
      • Portland, Oregon, United States, 97210
        • Legacy Good Samaritan Hospital and Medical Center
      • Portland, Oregon, United States, 97213
        • Providence Portland Medical Center
      • Portland, Oregon, United States, 97225
        • Providence Saint Vincent Medical Center
      • Portland, Oregon, United States, 97227
        • Kaiser Permanente Northwest
      • Portland, Oregon, United States, 97227
        • Legacy Emanuel Hospital and Health Center
      • Portland, Oregon, United States, 97216
        • Adventist Medical Center
      • Tualatin, Oregon, United States, 97062
        • Legacy Meridian Park Hospital
    • Pennsylvania
      • Abington, Pennsylvania, United States, 19001
        • Jefferson Abington Hospital
      • Allentown, Pennsylvania, United States, 18103
        • Lehigh Valley Hospital-Cedar Crest
      • Bryn Mawr, Pennsylvania, United States, 19010
        • Bryn Mawr Hospital
      • Doylestown, Pennsylvania, United States, 18901
        • Doylestown Hospital
      • Paoli, Pennsylvania, United States, 19301
        • Paoli Memorial Hospital
      • Pittsburgh, Pennsylvania, United States, 15224
        • West Penn Hospital
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Cancer Institute (UPCI)
      • Sayre, Pennsylvania, United States, 18840
        • Guthrie Medical Group PC-Robert Packer Hospital
      • Scranton, Pennsylvania, United States, 18510
        • Scranton Hematology Oncology
      • Scranton, Pennsylvania, United States, 18501
        • Mercy Hospital
      • Sellersville, Pennsylvania, United States, 18960
        • Grand View Hospital
      • West Chester, Pennsylvania, United States, 19380
        • Chester County Hospital
      • West Reading, Pennsylvania, United States, 19611
        • Reading Hospital
      • Williamsport, Pennsylvania, United States, 17701
        • UPMC Susquehanna
      • Wynnewood, Pennsylvania, United States, 19096
        • Lankenau Medical Center
    • Rhode Island
      • Cranston, Rhode Island, United States, 02920
        • Hematology and Oncology Associates of Rhode Island Inc
      • Pawtucket, Rhode Island, United States, 02860
        • Memorial Hospital of Rhode Island
      • Warwick, Rhode Island, United States, 02886
        • Kent Hospital
    • South Carolina
      • Anderson, South Carolina, United States, 29621
        • AnMed Health Cancer Center
      • Anderson, South Carolina, United States, 29621
        • AnMed Health Hospital
      • Florence, South Carolina, United States, 29506
        • McLeod Regional Medical Center
      • Greenville, South Carolina, United States, 29601
        • Saint Francis Hospital
      • Spartanburg, South Carolina, United States, 29303
        • Spartanburg Medical Center
    • South Dakota
      • Aberdeen, South Dakota, United States, 57401
        • Avera Cancer Institute-Aberdeen
      • Rapid City, South Dakota, United States, 57701
        • Rapid City Regional Hospital
      • Sioux Falls, South Dakota, United States, 57105
        • Avera Cancer Institute
      • Sioux Falls, South Dakota, United States, 57117-5134
        • Sanford USD Medical Center - Sioux Falls
      • Sioux Falls, South Dakota, United States, 57104
        • Sanford Cancer Center Oncology Clinic
      • Sioux Falls, South Dakota, United States, 57105
        • Medical X-Ray Center
      • Sioux Falls, South Dakota, United States, 57117-5045
        • Avera McKennan Hospital and University Health Center
    • Tennessee
      • Chattanooga, Tennessee, United States, 37403
        • Erlanger Medical Center
    • Texas
      • Laredo, Texas, United States, 78041
        • Doctor's Hospital of Laredo
    • Virginia
      • Charlottesville, Virginia, United States, 22901
        • Sentara Martha Jefferson Hospital
      • Danville, Virginia, United States, 24541
        • Danville Regional Medical Center
      • Fairfax, Virginia, United States, 22033
        • Kaiser Permanente - Fair Oaks Medical Center
    • Washington
      • Centralia, Washington, United States, 98531
        • Providence Regional Cancer System-Centralia
      • Federal Way, Washington, United States, 98003
        • Saint Francis Hospital
      • Lakewood, Washington, United States, 98499
        • Saint Clare Hospital
      • Olympia, Washington, United States, 98506-5166
        • Providence - Saint Peter Hospital
      • Puyallup, Washington, United States, 98372
        • MultiCare Good Samaritan Hospital
      • Spokane, Washington, United States, 99204
        • Providence Sacred Heart Medical Center and Children's Hospital
      • Spokane, Washington, United States, 99220
        • Rockwood Clinic
      • Spokane, Washington, United States, 99208
        • Providence Holy Family Hospital
      • Tacoma, Washington, United States, 98405
        • MultiCare Allenmore Hospital
      • Tacoma, Washington, United States, 98405
        • Saint Joseph Medical Center
      • Vancouver, Washington, United States, 98664
        • PeaceHealth Southwest Medical Center
    • West Virginia
      • Charleston, West Virginia, United States, 25304
        • West Virginia University Charleston Division
      • Wheeling, West Virginia, United States, 26003
        • Wheeling Hospital/Schiffler Cancer Center
    • Wisconsin
      • Antigo, Wisconsin, United States, 54409
        • Langlade Hospital and Cancer Center
      • Burlington, Wisconsin, United States, 53105
        • Aurora Cancer Care-Southern Lakes VLCC
      • Chippewa Falls, Wisconsin, United States, 54729
        • Marshfield Clinic-Chippewa Center
      • Eau Claire, Wisconsin, United States, 54701
        • Marshfield Clinic Cancer Center at Sacred Heart
      • Franklin, Wisconsin, United States, 53132
        • Aurora Cancer Care-Franklin
      • Germantown, Wisconsin, United States, 53022
        • Aurora Health Care Germantown Health Center
      • Glendale, Wisconsin, United States, 53212
        • Aurora Cancer Care-Glendale
      • Green Bay, Wisconsin, United States, 54311
        • Aurora BayCare Medical Center
      • Green Bay, Wisconsin, United States, 54301
        • Saint Vincent Hospital Cancer Center Green Bay
      • Green Bay, Wisconsin, United States, 54303
        • Saint Vincent Hospital Cancer Center at Saint Mary's
      • Green Bay, Wisconsin, United States, 54301
        • Bellin Memorial Hospital
      • Green Bay, Wisconsin, United States, 54303
        • Green Bay Oncology Limited at Saint Mary's Hospital
      • Green Bay, Wisconsin, United States, 54301-3526
        • Green Bay Oncology at Saint Vincent Hospital
      • Janesville, Wisconsin, United States, 53548
        • Mercyhealth Hospital and Cancer Center - Janesville
      • Kenosha, Wisconsin, United States, 53142
        • Aurora Cancer Care-Kenosha South
      • La Crosse, Wisconsin, United States, 54601
        • Gundersen Lutheran Medical Center
      • Madison, Wisconsin, United States, 53717
        • Dean Hematology and Oncology Clinic
      • Manitowoc, Wisconsin, United States, 54221
        • Holy Family Memorial Hospital
      • Marinette, Wisconsin, United States, 54143
        • Aurora Bay Area Medical Group-Marinette
      • Marinette, Wisconsin, United States, 54143
        • Bay Area Medical Center
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Medical Center-Marshfield
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Medical Center
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin
      • Milwaukee, Wisconsin, United States, 53215
        • Aurora Saint Luke's Medical Center
      • Milwaukee, Wisconsin, United States, 53233
        • Aurora Sinai Medical Center
      • Minocqua, Wisconsin, United States, 54548
        • Marshfield Clinic-Minocqua Center
      • Oconomowoc, Wisconsin, United States, 53066
        • ProHealth Oconomowoc Memorial Hospital
      • Oconto Falls, Wisconsin, United States, 54154
        • Saint Vincent Hospital Cancer Center at Oconto Falls
      • Oshkosh, Wisconsin, United States, 54904
        • Vince Lombardi Cancer Clinic - Oshkosh
      • Racine, Wisconsin, United States, 53406
        • Aurora Cancer Care-Racine
      • Rhinelander, Wisconsin, United States, 54501
        • Ascension Saint Mary's Hospital
      • Rice Lake, Wisconsin, United States, 54868
        • Marshfield Medical Center-Rice Lake
      • Sheboygan, Wisconsin, United States, 53081
        • Vince Lombardi Cancer Clinic-Sheboygan
      • Sheboygan, Wisconsin, United States, 53081
        • HSHS Saint Nicholas Hospital
      • Stevens Point, Wisconsin, United States, 54481
        • Ascension Saint Michael's Hospital
      • Sturgeon Bay, Wisconsin, United States, 54235
        • Green Bay Oncology - Sturgeon Bay
      • Summit, Wisconsin, United States, 53066
        • Aurora Medical Center in Summit
      • Two Rivers, Wisconsin, United States, 54241
        • Vince Lombardi Cancer Clinic-Two Rivers
      • Waukesha, Wisconsin, United States, 53188
        • ProHealth Waukesha Memorial Hospital
      • Waukesha, Wisconsin, United States, 53188
        • Aurora Cancer Care-Waukesha
      • Wausau, Wisconsin, United States, 54401
        • Aspirus Regional Cancer Center
      • Wauwatosa, Wisconsin, United States, 53226
        • Aurora Cancer Care-Milwaukee West
      • West Allis, Wisconsin, United States, 53227
        • Aurora West Allis Medical Center
      • Weston, Wisconsin, United States, 54476
        • Marshfield Medical Center - Weston
      • Wisconsin Rapids, Wisconsin, United States, 54494
        • Aspirus Cancer Care - Wisconsin Rapids
      • Wisconsin Rapids, Wisconsin, United States, 54494
        • Marshfield Clinic - Wisconsin Rapids Center
    • Wyoming
      • Casper, Wyoming, United States, 82609
        • Rocky Mountain Oncology
      • Sheridan, Wyoming, United States, 82801
        • Welch Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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
    • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I (endocrine therapy with monoclonal antibody)
Patients 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.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Questionnaire Administration
Ancillary studies
Biological: Bevacizumab
Given IV
Other Names:
  • Avastin
  • ABP 215
  • Anti-VEGF
  • Anti-VEGF Humanized Monoclonal Antibody
  • Anti-VEGF Monoclonal Antibody SIBP04
  • Anti-VEGF rhuMAb
  • Bevacizumab awwb
  • Bevacizumab Biosimilar ABP 215
  • Bevacizumab Biosimilar BEVZ92
  • Bevacizumab Biosimilar BI 695502
  • Bevacizumab Biosimilar CBT 124
  • Bevacizumab Biosimilar CT-P16
  • Bevacizumab Biosimilar FKB238
  • Bevacizumab Biosimilar GB-222
  • Bevacizumab Biosimilar HD204
  • Bevacizumab Biosimilar HLX04
  • Bevacizumab Biosimilar IBI305
  • Bevacizumab Biosimilar LY01008
  • Bevacizumab Biosimilar MIL60
  • Bevacizumab Biosimilar Mvasi
  • Bevacizumab Biosimilar MYL-1402O
  • Bevacizumab Biosimilar QL 1101
  • Bevacizumab Biosimilar RPH-001
  • Bevacizumab Biosimilar SCT501
  • Bevacizumab Biosimilar Zirabev
  • Bevacizumab-awwb
  • Bevacizumab-bvzr
  • BP102
  • BP102 Biosimilar
  • HD204
  • Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer
  • Mvasi
  • MYL-1402O
  • Recombinant Humanized Anti-VEGF Monoclonal Antibody
  • rhuMab-VEGF
  • SCT501
  • SIBP 04
  • SIBP-04
  • SIBP04
  • Zirabev
  • QL1101
  • Bevacizumab Biosimilar QL1101
  • BAT1706
  • BAT 1706
  • BAT-1706
  • BAT1706 Biosimilar
  • Bevacizumab Biosimilar BAT1706
  • Bevacizumab-adcd
  • CT-P16
  • Vegzelma
Drug: Letrozole
Given PO
Other Names:
  • CGS 20267
  • Femara
  • Fempro
Drug: Tamoxifen Citrate
Given PO
Other Names:
  • Nolvadex
  • TAM
  • Soltamox
  • Apo-Tamox
  • Clonoxifen
  • Dignotamoxi
  • Ebefen
  • Emblon
  • Estroxyn
  • Fentamox
  • Gen-Tamoxifen
  • Genox
  • ICI 46,474
  • ICI-46474
  • Jenoxifen
  • Kessar
  • Ledertam
  • Lesporene
  • Nolgen
  • Noltam
  • Nolvadex-D
  • Nourytam
  • Novo-Tamoxifen
  • Novofen
  • Noxitem
  • Oestrifen
  • Oncotam
  • PMS-Tamoxifen
  • Tamax
  • Tamaxin
  • Tamifen
  • Tamizam
  • Tamofen
  • Tamoxasta
  • Tamoxifeni Citras
  • Zemide
Active Comparator: Arm II (endocrine therapy)
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.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Questionnaire Administration
Ancillary studies
Drug: Letrozole
Given PO
Other Names:
  • CGS 20267
  • Femara
  • Fempro
Drug: Tamoxifen Citrate
Given PO
Other Names:
  • Nolvadex
  • TAM
  • Soltamox
  • Apo-Tamox
  • Clonoxifen
  • Dignotamoxi
  • Ebefen
  • Emblon
  • Estroxyn
  • Fentamox
  • Gen-Tamoxifen
  • Genox
  • ICI 46,474
  • ICI-46474
  • Jenoxifen
  • Kessar
  • Ledertam
  • Lesporene
  • Nolgen
  • Noltam
  • Nolvadex-D
  • Nourytam
  • Novo-Tamoxifen
  • Novofen
  • Noxitem
  • Oestrifen
  • Oncotam
  • PMS-Tamoxifen
  • Tamax
  • Tamaxin
  • Tamifen
  • Tamizam
  • Tamofen
  • Tamoxasta
  • Tamoxifeni Citras
  • Zemide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival
Time Frame: From randomization until disease progression or death whichever occurs first, assessed up to 5 years
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.
From randomization until disease progression or death whichever occurs first, assessed up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
12 Month Progression Free Survival Rate
Time Frame: At 12 months
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.
At 12 months
6 Month Progression-Free Survival Rate
Time Frame: At 6 months
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.
At 6 months
Objective Response Rate
Time Frame: Assessed up to 5 years
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.
Assessed up to 5 years
Overall Survival (OS)
Time Frame: Assessed up to 5 years
OS is defined as the time from study entry to death from any cause. The median OS was estimated using the Kaplan-Meier method.
Assessed up to 5 years
Duration of Tumor Response
Time Frame: From the time measurement criteria are met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years
Defined by RECIST criteria.
From the time measurement criteria are met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years
Probability of Surviving Until 36 Months
Time Frame: At 36 months
At 36 months
Site of Progression
Time Frame: Up to 5 years
Up to 5 years
Time-to-treatment Failure
Time Frame: Up to 5 years
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
Up to 5 years
Treatment Related Toxicity
Time Frame: Up to 5 years
Graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Tabulated by type, grade, and arm.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Hope S Rugo, Alliance for Clinical Trials in Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 15, 2008

Primary Completion (Actual)

June 30, 2014

Study Completion (Estimated)

July 10, 2024

Study Registration Dates

First Submitted

January 18, 2008

First Submitted That Met QC Criteria

January 24, 2008

First Posted (Estimated)

January 28, 2008

Study Record Updates

Last Update Posted (Actual)

April 4, 2024

Last Update Submitted That Met QC Criteria

April 3, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2009-00477 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180821 (U.S. NIH Grant/Contract)
  • U10CA031946 (U.S. NIH Grant/Contract)
  • CALGB-40503 (Other Identifier: CTEP)
  • CDR0000584091
  • CALGB 40503/CTSU 40503

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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