Chemotherapy With or Without Bevacizumab in Treating Women With Stage I, Stage II, or Stage IIIA Breast Cancer That Can Be Removed By Surgery

September 12, 2017 updated by: NSABP Foundation Inc

A Randomized Phase III Trial of Neoadjuvant Therapy in Patients With Palpable and Operable Breast Cancer Evaluating the Effect on Pathologic Complete Response (pCR) of Adding Capecitabine or Gemcitabine to Docetaxel When Administered Before AC With or Without Bevacizumab and Correlative Science Studies Attempting to Identify Predictors of High Likelihood for pCR With Each of the Regimens

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of breast cancer by blocking blood flow to the tumor. Giving chemotherapy and bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving bevacizumab after surgery may kill any tumor cells that remain after surgery. It is not yet known which chemotherapy regimen is more effective with or without bevacizumab in treating breast cancer.

PURPOSE: This randomized phase III trial is studying six different chemotherapy regimens to compare how well they work with or without bevacizumab in treating women with stage I, stage II, or stage IIIA breast cancer that can be removed by surgery.

Study Overview

Status

Unknown

Conditions

Breast Cancer

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

Compare the efficacy of docetaxel followed by doxorubicin hydrocloride and cyclophosphamide (AC) vs docetaxel and capecitabine followed by AC vs docetaxel and gemcitabine hydrochloride followed by AC, with or without bevacizumab, in terms of an increase in the rate of pathologic complete response (pCR) in the breast, in women with palpable or operable breast cancer.

Secondary

Compare docetaxel/capecitabine with AC vs docetaxel/gemcitabine hydrochloride with AC vs docetaxel with AC, with or without bevacizumab, in terms of the rate of pCR in the breast and all post-therapy lymph nodes evaluated histologically (pCR breast and nodes).
Determine whether the addition of bevacizumab to the docetaxel/anthracycline-based regimens (docetaxel with AC, docetaxel and capecitabine with AC, and docetaxel and gemcitabine hydrochloride with AC) will increase the rate of pCR of the breast and nodes compared to the same docetaxel/anthracycline-based regimens without bevacizumab in these patients.
Determine whether the addition of capecitabine or gemcitabine hydrochloride to docetaxel, with or without bevacizumab, will increase the rate of clinical overall response (cOR) compared to docetaxel alone with or without bevacizumab in these patients.
Determine whether the addition of bevacizumab to the docetaxel/anthracycline-based regimens will increase the rate of cOR compared to the same docetaxel/anthracycline-based regimens without bevacizumab in these patients.
Determine whether the addition of capecitabine or gemcitabine hydrochloride to docetaxel, with or without bevacizumab, will increase the rate of clinical complete response (cCR) compared to docetaxel alone with or without bevacizumab in these patients.
Determine whether the addition of bevacizumab to the docetaxel/anthracycline-based regimens (docetaxel with AC, docetaxel/capecitabine with AC, and docetaxel/gemcitabine hydrochloride with AC) will increase the rate of cCR compared to the same docetaxel/anthracycline-based regimens without bevacizumab in these patients.
Identify gene expression profiles that can predict pCR in patients treated with the different sequential docetaxel/anthracycline-based regimens with or without bevacizumab.
Identify gene expression profiles that can predict cOR in patients treated with docetaxel alone, docetaxel/capecitabine, or docetaxel/gemcitabine hydrochloride with or without bevacizumab.
Determine the accuracy of an in vitro chemoresponse assay (ChemoFx®) as a predictor of pCR in patients treated with the different sequential docetaxel/anthracycline-based regimens without bevacizumab.
Determine the accuracy of ChemoFx® as a predictor of cOR in patients treated with docetaxel alone, docetaxel/capecitabine, or docetaxel/gemcitabine hydrochloride without bevacizumab in these patients.
Determine the impact of preoperative bevacizumab and sequential chemotherapy regimens and postoperative bevacizumab therapy on cardiac function in these patients.
Determine the impact of bevacizumab on surgical complications in these patients.
Determine the toxicity of the preoperative regimens and the toxicity of postoperative bevacizumab in these patients.
Compare the docetaxel/anthracycline-based regimens with vs without bevacizumab, in terms of an increase in disease-free survival, of these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor size (2-4 cm vs > 4 cm), nodal status (negative vs positive), hormone receptor status (estrogen receptor [ER]-positive and/or progesterone-receptor [PgR]-positive vs ER- and PgR-negative), and age (< 50 years vs ≥ 50 years). Patients are randomized to 1 of 6 treatment arms.

Core needle biopsies are performed at baseline. Tumor tissue samples are also collected during definitive surgery. Samples are examined for gene expression and polymorphism by reverse transcriptase-polymerase chain reaction analysis and chemoresponse assay (ChemoFx®).

After completion of study therapy, patients are followed periodically for 10 years.

PROJECTED ACCRUAL: A total of 1,200 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Actual)

1206

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

Canada
- Ontario
  - Toronto, Ontario, Canada, M4N 3M5
    - Edmond Odette Cancer Centre at Sunnybrook
- Quebec
  - Montreal, Quebec, Canada, H3G 1A4
    - Montreal General Hospital
  - Montreal, Quebec, Canada, H3A 1A1
    - Royal Victoria Hospital - Montreal
  - Montreal, Quebec, Canada, H3T 1E2
    - Jewish General Hospital - Montreal
  - Montreal, Quebec, Canada, H2L 4M1
    - Hopital Notre-Dame du CHUM
  - Montreal, Quebec, Canada, H2W 1T8
    - CHUM - Hotel Dieu Hospital
  - Montreal, Quebec, Canada, H2X 3J4
    - CHUM - Hopital Saint-Luc
  - Montreal, Quebec, Canada, H3T 1M5
    - St. Mary's Hospital Center
  - Quebec City, Quebec, Canada, G1S 4L8
    - Hopital du Saint-Sacrement - Quebec
Puerto Rico
- - San Juan, Puerto Rico, 00928
    - San Juan City Hospital
United States
- Arkansas
  - Little Rock, Arkansas, United States, 72205
    - Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
- California
  - Castro Valley, California, United States, 94546
    - East Bay Radiation Oncology Center
  - Castro Valley, California, United States, 94546
    - Eden Medical Center
  - Castro Valley, California, United States, 94546
    - Valley Medical Oncology Consultants - Castro Valley
  - Fremont, California, United States, 94538
    - Kaiser Permanente - Fremont
  - Fremont, California, United States, 94538
    - Valley Medical Oncology
  - Fresno, California, United States, 93720
    - Cancer Care Associates
  - Hayward, California, United States, 94545
    - Kaiser Permanente Medical Center - Hayward
  - La Jolla, California, United States, 92037
    - Scripps Cancer Center - San Diego
  - Loma Linda, California, United States, 92354
    - Loma Linda University Cancer Institute at Loma Linda University Medical Center
  - Martinez, California, United States, 94553-3156
    - Contra Costa Regional Medical Center
  - Mountain View, California, United States, 94040
    - El Camino Hospital Cancer Center
  - Oakland, California, United States, 94609
    - Alta Bates Summit Medical Center - Summit Campus
  - Oakland, California, United States, 94602
    - Highland General Hospital
  - Oakland, California, United States, 94609
    - Larry G Strieff MD Medical Corporation
  - Oakland, California, United States, 94609
    - CCOP - Bay Area Tumor Institute
  - Oakland, California, United States, 94609
    - Bay Area Breast Surgeons, Incorporated
  - Oakland, California, United States, 94609
    - Tom K Lee, Incorporated
  - Oakland, California, United States, 94611
    - Kaiser Permanente Medical Center - Oakland
  - Orange, California, United States, 92868
    - St. Joseph Hospital Regional Cancer Center - Orange
  - Palm Springs, California, United States, 92262
    - Desert Regional Medical Center Comprehensive Cancer Center
  - Pleasanton, California, United States, 94588
    - Valley Care Medical Center
  - Pleasanton, California, United States, 94588
    - Valley Medical Oncology Consultants - Pleasanton
  - Redwood City, California, United States, 94063
    - Kaiser Permanente Medical Center - Redwood City
  - Richmond, California, United States, 94801
    - Kaiser Permanente Medical Center - Richmond
  - Roseville, California, United States, 95661
    - Kaiser Permanente Medical Center - Roseville
  - Sacramento, California, United States, 95823
    - South Sacramento Kaiser-Permanente Medical Center
  - Sacramento, California, United States, 95825
    - Kaiser Permanente Medical Center - Sacramento
  - Salinas, California, United States, 93901
    - Salinas Valley Memorial Hospital
  - San Diego, California, United States, 92120
    - Kaiser Permanente Medical Office -Vandever Medical Office
  - San Francisco, California, United States, 94115
    - Kaiser Permanente Medical Center - San Francisco Geary Campus
  - San Jose, California, United States, 95119
    - Kaiser Permanente Medical Center - Santa Teresa
  - San Pablo, California, United States, 94806
    - Doctors Medical Center - San Pablo Campus
  - San Rafael, California, United States, 94903
    - Kaiser Foundation Hospital - San Rafael
  - Santa Clara, California, United States, 95051
    - Kaiser Permanente Medical Center - Santa Clara Kiely Campus
  - Santa Rosa, California, United States, 95403
    - Kaiser Permanente Medical Center - Santa Rosa
  - South San Francisco, California, United States, 94080
    - Kaiser Permanente Medical Center - South San Francisco
  - Stockton, California, United States, 95210
    - Kaiser Permanente Medical Facility - Stockton
  - Vallejo, California, United States, 94589
    - Kaiser Permanente Medical Center - Vallejo
  - Walnut Creek, California, United States, 94596
    - Kaiser Permanente Medical Center - Walnut Creek
- Colorado
  - Aurora, Colorado, United States, 80012
    - Aurora Presbyterian Hospital
  - Boulder, Colorado, United States, 80301-9019
    - Boulder Community Hospital
  - Colorado Springs, Colorado, United States, 80933
    - Penrose Cancer Center at Penrose Hospital
  - Colorado Springs, Colorado, United States, 80909
    - Memorial Hospital Cancer Center - Colorado Springs
  - Denver, Colorado, United States, 80210
    - Porter Adventist Hospital
  - Denver, Colorado, United States, 80220
    - Rose Medical Center
  - Denver, Colorado, United States, 80218
    - Presbyterian - St. Luke's Medical Center
  - Denver, Colorado, United States, 80204
    - St. Anthony Central Hospital
  - Denver, Colorado, United States, 80218
    - St. Joseph Hospital
  - Denver, Colorado, United States, 80224-2522
    - CCOP - Colorado Cancer Research Program
  - Denver, Colorado, United States, 80205
    - Kaiser Permanente - Denver
  - Englewood, Colorado, United States, 80110
    - Swedish Medical Center
  - Grand Junction, Colorado, United States, 81502
    - St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
  - Greeley, Colorado, United States, 80631
    - North Colorado Medical Center
  - Lafayette, Colorado, United States, 80026
    - Kaiser Permanente - Lafayette
  - Lone Tree, Colorado, United States, 80124
    - Sky Ridge Medical Center
  - Longmont, Colorado, United States, 80501
    - Hope Cancer Care Center at Longmont United Hospital
  - Loveland, Colorado, United States, 80539
    - McKee Medical Center
  - Pueblo, Colorado, United States, 81004
    - St. Mary - Corwin Regional Medical Center
  - Thornton, Colorado, United States, 80229
    - North Suburban Medical Center
  - Wheat Ridge, Colorado, United States, 80033
    - Exempla Lutheran Medical Center
- Connecticut
  - Farmington, Connecticut, United States, 06360-2875
    - Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
  - Hartford, Connecticut, United States, 06105
    - Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
  - Hartford, Connecticut, United States, 06102-5037
    - Helen and Harry Gray Cancer Center at Hartford Hospital
  - Norwich, Connecticut, United States, 06360
    - Eastern Connecticut Hematology and Oncology Associates
- Delaware
  - Lewes, Delaware, United States, 19958
    - Tunnell Cancer Center at Beebe Medical Center
  - Newark, Delaware, United States, 19713
    - CCOP - Christiana Care Health Services
- District of Columbia
  - Washington, D.C., District of Columbia, United States, 20016
    - Sibley Memorial Hospital
- Florida
  - Daytona Beach, Florida, United States, 32114
    - Herbert D. Kerman Regional Oncology Center - Daytona Beach
  - Fort Lauderdale, Florida, United States, 33316
    - Broward General Medical Center Cancer Center
  - Fort Lauderdale, Florida, United States, 33308
    - Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
  - Jacksonville, Florida, United States, 32207
    - Baptist Cancer Institute - Jacksonville
  - Jupiter, Florida, United States, 33458
    - Ella Milbank Foshay Cancer Center at Jupiter Medical Center
  - Miami Beach, Florida, United States, 33140
    - CCOP - Mount Sinai Medical Center
  - Orlando, Florida, United States, 32803-1273
    - Florida Hospital Cancer Institute at Florida Hospital Orlando
  - Orlando, Florida, United States, 32806
    - M.D. Anderson Cancer Center at Orlando
- Georgia
  - Albany, Georgia, United States, 31701
    - Phoebe Cancer Center at Phoebe Putney Memorial Hospital
  - Gainesville, Georgia, United States, 30501
    - Northeast Georgia Medical Center
  - Savannah, Georgia, United States, 31403-3089
    - Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
  - Savannah, Georgia, United States, 31405
    - Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
- Hawaii
  - 'Aiea, Hawaii, United States, 96701
    - Kapiolani Medical Center at Pali Momi
  - Honolulu, Hawaii, United States, 96813
    - Cancer Research Center of Hawaii
  - Honolulu, Hawaii, United States, 96826
    - Kapiolani Medical Center for Women and Children
  - Honolulu, Hawaii, United States, 96813
    - OnCare Hawaii, Incorporated - Lusitana
  - Honolulu, Hawaii, United States, 96813
    - Queen's Cancer Institute at Queen's Medical Center
  - Honolulu, Hawaii, United States, 96813
    - Straub Clinic and Hospital, Incorporated
  - Honolulu, Hawaii, United States, 96817
    - Hawaii Medical Center - East
  - Honolulu, Hawaii, United States, 96817
    - OnCare Hawaii, Incorporated - Kuakini
  - Honolulu, Hawaii, United States, 96819
    - Kaiser Permanente - Moanalua Medical Center and Clinic
  - Wailuku, Hawaii, United States, 96793
    - Maui Memorial Medical Center
  - Wailuku, Hawaii, United States, 96793
    - Pacific Cancer Institute - Maui
- Idaho
  - Coeur d'Alene, Idaho, United States, 83814
    - Kootenai Cancer Center - Coeur d'Alene
- Illinois
  - Alton, Illinois, United States, 62002
    - Saint Anthony's Hospital at Saint Anthony's Health Center
  - Bloomington, Illinois, United States, 61701
    - Illinois CancerCare - Bloomington
  - Bloomington, Illinois, United States, 61701
    - St. Joseph Medical Center
  - Canton, Illinois, United States, 61520
    - Illinois CancerCare - Canton
  - Canton, Illinois, United States, 61520
    - Graham Hospital
  - Carthage, Illinois, United States, 62321
    - Memorial Hospital
  - Carthage, Illinois, United States, 62321
    - Illinois CancerCare - Carthage
  - Chicago, Illinois, United States, 60612
    - Rush University Medical Center
  - Chicago, Illinois, United States, 60608
    - Mount Sinai Hospital Medical Center
  - Chicago, Illinois, United States, 60612-3785
    - John H. Stroger, Jr. Hospital of Cook County
  - Decatur, Illinois, United States, 62526
    - Decatur Memorial Hospital Cancer Care Institute
  - Elk Grove Village, Illinois, United States, 60007
    - Alexian Brothers Radiation Oncology
  - Eureka, Illinois, United States, 61530
    - Illinois CancerCare - Eureka
  - Eureka, Illinois, United States, 61530
    - Eureka Community Hospital
  - Evanston, Illinois, United States, 60202
    - St. Francis Hospital
  - Galesburg, Illinois, United States, 61401
    - Illinois CancerCare - Galesburg
  - Galesburg, Illinois, United States, 61401
    - Galesburg Cottage Hospital
  - Galesburg, Illinois, United States, 61401
    - Galesburg Clinic, PC
  - Galesburg, Illinois, United States, 61401
    - Illinois CancerCare - Cottage
  - Havana, Illinois, United States, 62644
    - Mason District Hospital
  - Havana, Illinois, United States, 62644
    - Illinois CancerCare - Havana
  - Kewanee, Illinois, United States, 61443
    - Illinois CancerCare - Kewanee Clinic
  - Macomb, Illinois, United States, 61455
    - Illinois CancerCare - Macomb
  - Macomb, Illinois, United States, 61455
    - Mcdonough District Hospital
  - Maywood, Illinois, United States, 60153
    - Cardinal Bernardin Cancer Center at Loyola University Medical Center
  - Monmouth, Illinois, United States, 61462
    - Illinois CancerCare - Monmouth
  - Monmouth, Illinois, United States, 61462
    - OSF Holy Family Medical Center
  - Mount Vernon, Illinois, United States, 62864
    - Good Samaritan Regional Health Center
  - Naperville, Illinois, United States, 60540
    - Edward Hospital Cancer Center
  - Normal, Illinois, United States, 61761
    - Bromenn Regional Medical Center
  - Normal, Illinois, United States, 61761
    - Community Cancer Center
  - Normal, Illinois, United States, 61761
    - Illinois CancerCare - Community Cancer Center
  - Ottawa, Illinois, United States, 61350
    - Community Hospital of Ottawa
  - Ottawa, Illinois, United States, 61350
    - Oncology Hematology Associates of Central Illinois, PC - Ottawa
  - Pekin, Illinois, United States, 61603
    - Illinois CancerCare - Pekin
  - Peoria, Illinois, United States, 61636
    - Methodist Medical Center of Illinois
  - Peoria, Illinois, United States, 61614
    - Proctor Hospital
  - Peoria, Illinois, United States, 61637
    - OSF St. Francis Medical Center
  - Peoria, Illinois, United States, 61615
    - CCOP - Illinois Oncology Research Association
  - Peoria, Illinois, United States, 61615
    - Oncology Hematology Associates of Central Illinois, PC - Peoria
  - Peru, Illinois, United States, 61354
    - Illinois CancerCare - Peru
  - Peru, Illinois, United States, 61354
    - Illinois Valley Community Hospital
  - Princeton, Illinois, United States, 61356
    - Perry Memorial Hospital
  - Princeton, Illinois, United States, 61356
    - Illinois CancerCare - Princeton
  - Rockford, Illinois, United States, 61104-2315
    - Swedish-American Regional Cancer Center
  - Spring Valley, Illinois, United States, 61362
    - Illinois CancerCare - Spring Valley
  - Springfield, Illinois, United States, 62781-0001
    - Regional Cancer Center at Memorial Medical Center
- Indiana
  - Beech Grove, Indiana, United States, 46107
    - St. Francis Hospital and Health Centers - Beech Grove Campus
  - Elkhart, Indiana, United States, 46515
    - Elkhart General Hospital
  - Elkhart, Indiana, United States, 46514-2098
    - Elkhart Clinic, LLC
  - Fort Wayne, Indiana, United States, 46845
    - Fort Wayne Medical Oncology and Hematology
  - Goshen, Indiana, United States, 46526
    - Center for Cancer Care at Goshen General Hospital
  - Indianapolis, Indiana, United States, 46260
    - St. Vincent Indianapolis Hospital
  - Kokomo, Indiana, United States, 46904
    - Howard Community Hospital
  - La Porte, Indiana, United States, 46350
    - Center for Cancer Therapy at LaPorte Hospital and Health Services
  - Munster, Indiana, United States, 46321
    - Community Hospital
  - Richmond, Indiana, United States, 47374
    - Reid Hospital & Health Care Services
  - South Bend, Indiana, United States, 46601
    - Memorial Hospital of South Bend
  - South Bend, Indiana, United States, 46601
    - CCOP - Northern Indiana CR Consortium
  - South Bend, Indiana, United States, 46617
    - Saint Joseph Regional Medical Center
  - South Bend, Indiana, United States, 46617
    - South Bend Clinic
  - South Bend, Indiana, United States, 46601
    - Michiana Hematology-Oncology, PC - South Bend
- Iowa
  - Ames, Iowa, United States, 50010
    - McFarland Clinic, PC
  - Iowa City, Iowa, United States, 52242-1002
    - Holden Comprehensive Cancer Center at University of Iowa
- Kansas
  - Chanute, Kansas, United States, 66720
    - Cancer Center of Kansas, PA - Chanute
  - Dodge City, Kansas, United States, 67801
    - Cancer Center of Kansas, PA - Dodge City
  - El Dorado, Kansas, United States, 67042
    - Cancer Center of Kansas, PA - El Dorado
  - Fort Scott, Kansas, United States, 66701
    - Cancer Center of Kansas - Fort Scott
  - Independence, Kansas, United States, 67301
    - Cancer Center of Kansas-Independence
  - Kingman, Kansas, United States, 67068
    - Cancer Center of Kansas, PA - Kingman
  - Lawrence, Kansas, United States, 66044
    - Lawrence Memorial Hospital
  - Liberal, Kansas, United States, 67901
    - Southwest Medical Center
  - Newton, Kansas, United States, 67114
    - Cancer Center of Kansas, PA - Newton
  - Overland Park, Kansas, United States, 66209
    - Menorah Medical Center
  - Overland Park, Kansas, United States, 66213
    - Saint Luke's Hospital - South
  - Parsons, Kansas, United States, 67357
    - Cancer Center of Kansas, PA - Parsons
  - Pratt, Kansas, United States, 67124
    - Cancer Center of Kansas, PA - Pratt
  - Salina, Kansas, United States, 67401
    - Cancer Center of Kansas, PA - Salina
  - Shawnee, Kansas, United States, 66204
    - Shawnee Mission Medical Center
  - Wellington, Kansas, United States, 67152
    - Cancer Center of Kansas, PA - Wellington
  - Wichita, Kansas, United States, 67214
    - Wesley Medical Center
  - Wichita, Kansas, United States, 67208
    - Cancer Center of Kansas, PA - Medical Arts Tower
  - Wichita, Kansas, United States, 67214
    - Cancer Center of Kansas, PA - Wichita
  - Wichita, Kansas, United States, 67214
    - CCOP - Wichita
  - Wichita, Kansas, United States, 67214
    - Via Christi Cancer Center at Via Christi Regional Medical Center
  - Wichita, Kansas, United States, 67208
    - Associates in Womens Health, PA - North Review
  - Winfield, Kansas, United States, 67156
    - Cancer Center of Kansas, PA - Winfield
- Kentucky
  - Ashland, Kentucky, United States, 41101-0151
    - Cancer Resource Center at King's Daughters Medical Center
  - Lexington, Kentucky, United States, 40536-0093
    - Lucille P. Markey Cancer Center at University of Kentucky
  - Louisville, Kentucky, United States, 40202
    - Louisville Oncology at Norton Cancer Institute - Louisville
  - Louisville, Kentucky, United States, 40292
    - James Graham Brown Cancer Center at University of Louisville
- Louisiana
  - Baton Rouge, Louisiana, United States, 70809
    - Mary Bird Perkins Cancer Center - Baton Rouge
  - Baton Rouge, Louisiana, United States, 70809
    - Ochsner Health Center - Bluebonnet
  - New Orleans, Louisiana, United States, 70121
    - CCOP - Ochsner
  - New Orleans, Louisiana, United States, 70112
    - MBCCOP - LSU Health Sciences Center
  - New Orleans, Louisiana, United States, 70121
    - Ochsner Cancer Institute at Ochsner Clinic Foundation
  - New Orleans, Louisiana, United States, 70112
    - Medical Center of Louisiana - New Orleans
- Maine
  - York, Maine, United States, 03909
    - York Hospital's Oncology Treatment Center
- Maryland
  - Baltimore, Maryland, United States, 21229
    - St. Agnes Hospital Cancer Center
  - Baltimore, Maryland, United States, 21201
    - Greenebaum Cancer Center at University of Maryland Medical Center
  - Baltimore, Maryland, United States, 21204
    - Greater Baltimore Medical Center Cancer Center
  - Baltimore, Maryland, United States, 21237
    - Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center
  - Frederick, Maryland, United States, 21701
    - Frederick Memorial Hospital Regional Cancer Therapy Center
  - Rockville, Maryland, United States, 20878
    - Associates in Oncology and Hematology - Medical Center Drive
  - Salisbury, Maryland, United States, 21801
    - Peninsula Regional Medical Center
- Massachusetts
  - Framingham, Massachusetts, United States, 01702
    - Metrowest Medical Center - Framingham Union Hospital
- Michigan
  - Adrian, Michigan, United States, 49221
    - Hickman Cancer Center at Bixby Medical Center
  - Ann Arbor, Michigan, United States, 48106-0995
    - Saint Joseph Mercy Cancer Center
  - Ann Arbor, Michigan, United States, 48106
    - CCOP - Michigan Cancer Research Consortium
  - Dearborn, Michigan, United States, 48123-2500
    - Oakwood Cancer Center at Oakwood Hospital and Medical Center
  - Detroit, Michigan, United States, 48202
    - Josephine Ford Cancer Center at Henry Ford Hospital
  - Flint, Michigan, United States, 48503
    - Hurley Medical Center
  - Flint, Michigan, United States, 48503
    - Genesys Hurley Cancer Institute
  - Flint, Michigan, United States, 48532
    - Great Lakes Cancer Institute at McLaren Regional Medical Center
  - Grosse Pointe Woods, Michigan, United States, 48236
    - Van Elslander Cancer Center at St. John Hospital and Medical Center
  - Jackson, Michigan, United States, 49201
    - Foote Memorial Hospital
  - Kalamazoo, Michigan, United States, 49007
    - Bronson Methodist Hospital
  - Kalamazoo, Michigan, United States, 49001
    - Borgess Medical Center
  - Kalamazoo, Michigan, United States, 49007-3731
    - West Michigan Cancer Center
  - Lambertville, Michigan, United States, 48144
    - Haematology-Oncology Associates of Ohio and Michigan, PC
  - Lansing, Michigan, United States, 48912-1811
    - Sparrow Regional Cancer Center
  - Lansing, Michigan, United States, 48910
    - Breslin Cancer Center at Ingham Regional Medical Center
  - Lapeer, Michigan, United States, 48446
    - Lapeer Regional Hospital
  - Livonia, Michigan, United States, 48154
    - St. Mary Mercy Hospital
  - Monroe, Michigan, United States, 48162
    - Community Cancer Center of Monroe
  - Monroe, Michigan, United States, 48162
    - Mercy Memorial Hospital - Monroe
  - Pontiac, Michigan, United States, 48341-2985
    - St. Joseph Mercy Oakland
  - Port Huron, Michigan, United States, 48060
    - Mercy Regional Cancer Center at Mercy Hospital
  - Saginaw, Michigan, United States, 48601
    - Seton Cancer Institute at Saint Mary's - Saginaw
  - Saint Joseph, Michigan, United States, 49085
    - Lakeside Cancer Specialists, PLLC
  - Saint Joseph, Michigan, United States, 49085
    - Lakeland Regional Cancer Care Center - St. Joseph
  - Southfield, Michigan, United States, 48075
    - Providence Cancer Institute at Providence Hospital - Southfield Campus
  - Warren, Michigan, United States, 48093
    - St. John Macomb Hospital
- Minnesota
  - Burnsville, Minnesota, United States, 55337
    - Fairview Ridges Hospital
  - Coon Rapids, Minnesota, United States, 55433
    - Mercy and Unity Cancer Center at Mercy Hospital
  - Duluth, Minnesota, United States, 55805
    - CCOP - Duluth
  - Duluth, Minnesota, United States, 55805-1983
    - Duluth Clinic Cancer Center - Duluth
  - Duluth, Minnesota, United States, 55805
    - Miller - Dwan Medical Center
  - Edina, Minnesota, United States, 55435
    - Fairview Southdale Hospital
  - Fridley, Minnesota, United States, 55432
    - Mercy and Unity Cancer Center at Unity Hospital
  - Hutchinson, Minnesota, United States, 55350
    - Hutchinson Area Health Care
  - Maplewood, Minnesota, United States, 55109
    - Minnesota Oncology Hematology, PA - Maplewood
  - Maplewood, Minnesota, United States, 55109
    - HealthEast Cancer Care at St. John's Hospital
  - Minneapolis, Minnesota, United States, 55407
    - Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
  - Minneapolis, Minnesota, United States, 55415
    - Hennepin County Medical Center - Minneapolis
  - Robbinsdale, Minnesota, United States, 55422-2900
    - Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
  - Saint Louis Park, Minnesota, United States, 55416
    - CCOP - Metro-Minnesota
  - Saint Louis Park, Minnesota, United States, 55416
    - Park Nicollet Cancer Center
  - Saint Paul, Minnesota, United States, 55102
    - United Hospital
  - Saint Paul, Minnesota, United States, 55101
    - Regions Hospital Cancer Care Center
  - Shakopee, Minnesota, United States, 55379
    - St. Francis Cancer Center at St. Francis Medical Center
  - Waconia, Minnesota, United States, 55387
    - Ridgeview Medical Center
  - Woodbury, Minnesota, United States, 55125
    - Minnesota Oncology Hematology, PA - Woodbury
- Mississippi
  - Hattiesburg, Mississippi, United States, 39401
    - Hattiesburg Clinic, PA at Forrest General
- Missouri
  - Cape Girardeau, Missouri, United States, 63703
    - Saint Francis Medical Center
  - Columbia, Missouri, United States, 65203
    - Ellis Fischel Cancer Center at University of Missouri - Columbia
  - Joplin, Missouri, United States, 64804
    - St. John's Regional Medical Center
  - Kansas City, Missouri, United States, 64131
    - CCOP - Kansas City
  - Kansas City, Missouri, United States, 64116
    - North Kansas City Hospital
  - Kansas City, Missouri, United States, 64132
    - Research Medical Center
  - Kansas City, Missouri, United States, 64108
    - Truman Medical Center - Hospital Hill
  - Kansas City, Missouri, United States, 64111
    - Saint Luke's Cancer Institute at Saint Luke's Hospital
  - Kansas City, Missouri, United States, 64114
    - St. Joseph Medical Center
  - Kansas City, Missouri, United States, 64116
    - Parvin Radiation Oncology
  - Kansas City, Missouri, United States, 64118
    - Heartland Hematology Oncology Associates, Incorporated
  - Lee's Summit, Missouri, United States, 64086
    - Saint Luke's East - Lee's Summit
  - Liberty, Missouri, United States, 64068
    - Liberty Hospital
  - Saint Joseph, Missouri, United States, 64506
    - Heartland Regional Medical Center
  - Saint Louis, Missouri, United States, 63141
    - CCOP - St. Louis-Cape Girardeau
  - Saint Louis, Missouri, United States, 63110
    - Saint Louis University Cancer Center
  - Saint Louis, Missouri, United States, 63109
    - Midwest Hematology Oncology Group, Incorporated
  - Saint Louis, Missouri, United States, 63141
    - David C. Pratt Cancer Center at St. John's Mercy
  - Springfield, Missouri, United States, 65802
    - CCOP - Cancer Research for the Ozarks
  - Springfield, Missouri, United States, 65804
    - St. John's Regional Health Center
  - Springfield, Missouri, United States, 65807
    - Hulston Cancer Center at Cox Medical Center South
- Montana
  - Billings, Montana, United States, 59101
    - CCOP - Montana Cancer Consortium
  - Billings, Montana, United States, 59101
    - Hematology-Oncology Centers of the Northern Rockies - Billings
  - Billings, Montana, United States, 59101
    - Northern Rockies Radiation Oncology Center
  - Billings, Montana, United States, 59101
    - St. Vincent Healthcare Cancer Care Services
  - Billings, Montana, United States, 59107-7000
    - Billings Clinic - Downtown
  - Bozeman, Montana, United States, 59715
    - Bozeman Deaconess Cancer Center
  - Butte, Montana, United States, 59701
    - St. James Healthcare Cancer Care
  - Great Falls, Montana, United States, 59405
    - Great Falls Clinic - Main Facility
  - Great Falls, Montana, United States, 59405
  - Great Falls, Montana, United States, 59405-5309
    - Big Sky Oncology
  - Great Falls, Montana, United States, 59405
    - Sletten Cancer Institute at Benefis Healthcare
  - Helena, Montana, United States, 59601
    - St. Peter's 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 at KRMC
  - Missoula, Montana, United States, 59801
    - Community Medical Center
  - Missoula, Montana, United States, 59804
    - Guardian Oncology and Center for Wellness
  - Missoula, Montana, United States, 59807-7877
    - Montana Cancer Specialists at Montana Cancer Center
  - Missoula, Montana, United States, 59807
    - Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
- Nebraska
  - Kearney, Nebraska, United States, 68848-1990
    - Good Samaritan Cancer Center at Good Samaritan Hospital
  - Lincoln, Nebraska, United States, 68510
    - Cancer Resource Center - Lincoln
  - Omaha, Nebraska, United States, 68106
    - CCOP - Missouri Valley Cancer Consortium
  - Omaha, Nebraska, United States, 68122
    - Immanuel Medical Center
  - Omaha, Nebraska, United States, 68124
    - Alegant Health Cancer Center at Bergan Mercy Medical Center
  - Omaha, Nebraska, United States, 68131-2197
    - Creighton University Medical Center
- New Jersey
  - Hamilton, New Jersey, United States, 08690
    - Cancer Institute of New Jersey At Hamilton
  - New Brunswick, New Jersey, United States, 08903
    - Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
  - Newark, New Jersey, United States, 07112
    - Newark Beth Israel Medical Center
  - Voorhees, New Jersey, United States, 08043
    - Cancer Institute of New Jersey at Cooper - Voorhees
- New York
  - Glens Falls, New York, United States, 12801
    - Charles R. Wood Cancer Center at Glens Falls Hospital
  - Middletown, New York, United States, 10940-4199
    - Tucker Center for Cancer Care at Orange Regional Medical Center
  - Poughkeepsie, New York, United States, 12601
    - Saint Francis Hospital Cancer Center
  - The Bronx, New York, United States, 10466
    - Our Lady of Mercy Medical Center Comprehensive Cancer Center
- North Carolina
  - Asheboro, North Carolina, United States, 27203-5400
    - Randolph Hospital
  - Asheville, North Carolina, United States, 28816
    - Hope A Women's Cancer Center
  - Burlington, North Carolina, United States, 27216
    - Alamance Cancer Center at Alamance Regional Medical Center
  - Charlotte, North Carolina, United States, 28232-2861
    - Blumenthal Cancer Center at Carolinas Medical Center
  - Charlotte, North Carolina, United States, 28233-3549
    - Presbyterian Cancer Center at Presbyterian Hospital
  - Concord, North Carolina, United States, 28025
    - Batte Cancer Center at Northeast Medical Center
  - Goldsboro, North Carolina, United States, 27534
    - Wayne Memorial Hospital, Incorporated
  - Greensboro, North Carolina, United States, 27403-1198
    - Moses Cone Regional Cancer Center at Wesley Long Community Hospital
  - Reidsville, North Carolina, United States, 27320
    - Annie Penn Cancer Center
  - Rutherfordton, North Carolina, United States, 28139
    - Rutherford Hospital
  - Statesville, North Carolina, United States, 28677
    - Iredell Memorial Hospital
  - Washington, North Carolina, United States, 27889
    - Marion L. Shepard Cancer Center at Beaufort County Hospital
  - Winston-Salem, North Carolina, United States, 27157-1096
    - Wake Forest University Comprehensive Cancer Center
  - Winston-Salem, North Carolina, United States, 27103
    - Forsyth Regional Cancer Center at Forsyth Medical Center
- North Dakota
  - Grand Forks, North Dakota, United States, 58201
    - Altru Cancer Center at Altru Hospital
- Ohio
  - Akron, Ohio, United States, 44307
    - McDowell Cancer Center at Akron General Medical Center
  - Akron, Ohio, United States, 44309-2090
    - Summa Center for Cancer Care at Akron City Hospital
  - Barberton, Ohio, United States, 44203
    - Barberton Citizens Hospital
  - Bowling Green, Ohio, United States, 43402
    - Wood County Oncology Center
  - Canton, Ohio, United States, 44710-1799
    - Aultman Cancer Center at Aultman Hospital
  - Cleveland, Ohio, United States, 44106-5065
    - Case Comprehensive Cancer Center
  - Clyde, Ohio, United States, 43410
    - North Coast Cancer Care - Clyde
  - Columbus, Ohio, United States, 43210-1240
    - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
  - Dayton, Ohio, United States, 45405
    - Grandview Hospital
  - Dayton, Ohio, United States, 45406
    - Good Samaritan Hospital
  - Dayton, Ohio, United States, 45409
    - David L. Rike Cancer Center at Miami Valley Hospital
  - Dayton, Ohio, United States, 45415
    - Samaritan North Cancer Care Center
  - Dayton, Ohio, United States, 45420
    - CCOP - Dayton
  - Elyria, Ohio, United States, 44035
    - Community Cancer Center
  - Elyria, Ohio, United States, 44035
    - Hematology Oncology Center
  - Findlay, Ohio, United States, 45840
    - Blanchard Valley Medical Associates
  - Franklin, Ohio, United States, 45005-1066
    - Middletown Regional Hospital
  - Greenville, Ohio, United States, 45331
    - Wayne Hospital
  - Kettering, Ohio, United States, 45429
    - Charles F. Kettering Memorial Hospital
  - Lima, Ohio, United States, 45804
    - Lima Memorial Hospital
  - Maumee, Ohio, United States, 43537
    - St. Luke's Hospital
  - Maumee, Ohio, United States, 43537-1839
    - Northwest Ohio Oncology Center
  - Norwalk, Ohio, United States, 44857
    - Fisher-Titus Medical Center
  - Oregon, Ohio, United States, 43616
    - St. Charles Mercy Hospital
  - Oregon, Ohio, United States, 43616
    - Toledo Clinic - Oregon
  - Salem, Ohio, United States, 44460
    - Cancer Care Center, Incorporated
  - Sandusky, Ohio, United States, 44870
    - North Coast Cancer Care, Incorporated
  - Sylvania, Ohio, United States, 43560
    - Flower Hospital Cancer Center
  - Tiffin, Ohio, United States, 44883
    - Mercy Hospital of Tiffin
  - Toledo, Ohio, United States, 43608
    - St. Vincent Mercy Medical Center
  - Toledo, Ohio, United States, 43606
    - Toledo Hospital
  - Toledo, Ohio, United States, 43614
    - Medical University of Ohio Cancer Center
  - Toledo, Ohio, United States, 43617
    - CCOP - Toledo Community Hospital
  - Toledo, Ohio, United States, 43623
    - Toledo Clinic, Incorporated - Main Clinic
  - Toledo, Ohio, United States, 43623
    - St. Anne Mercy Hospital
  - Troy, Ohio, United States, 45373-1300
    - UVMC Cancer Care Center at Upper Valley Medical Center
  - Wauseon, Ohio, United States, 43567
    - Fulton County Health Center
  - Wilmington, Ohio, United States, 45177
    - Clinton Memorial Hospital
  - Wooster, Ohio, United States, 44691
    - Cancer Treatment Center
  - Xenia, Ohio, United States, 45385
    - Ruth G. McMillan Cancer Center at Greene Memorial Hospital
- Oklahoma
  - Lawton, Oklahoma, United States, 73505
    - Cleo Craig Cancer Research Clinic
- Oregon
  - Portland, Oregon, United States, 97232
    - Kaiser Permanente Health Care - Portland
- Pennsylvania
  - Allentown, Pennsylvania, United States, 18105
    - Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
  - Bethlehem, Pennsylvania, United States, 18015
    - St. Luke's Cancer Network at St. Luke's Hospital
  - Bryn Mawr, Pennsylvania, United States, 19010
    - Bryn Mawr Hospital
  - Danville, Pennsylvania, United States, 17822-0001
    - Geisinger Cancer Institute at Geisinger Health
  - Hanover, Pennsylvania, United States, 17331
    - Cherry Tree Cancer Center
  - Hershey, Pennsylvania, United States, 17033-0850
    - Penn State Cancer Institute at Milton S. Hershey Medical Center
  - Paoli, Pennsylvania, United States, 19301-1792
    - Cancer Center of Paoli Memorial Hospital
  - Pittsburgh, Pennsylvania, United States, 15232
    - UPMC Cancer Centers
  - Pittsburgh, Pennsylvania, United States, 15212
    - Allegheny Cancer Center at Allegheny General Hospital
  - Pittsburgh, Pennsylvania, United States, 15224-1791
    - Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
  - Reading, Pennsylvania, United States, 19612-6052
    - McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
  - State College, Pennsylvania, United States, 16803
    - Mount Nittany Medical Center
  - State College, Pennsylvania, United States, 16801
    - Geisinger Medical Group - Scenery Park
  - Wilkes-Barre, Pennsylvania, United States, 18711
    - Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
  - Wynnewood, Pennsylvania, United States, 19096
    - Lankenau Cancer Center at Lankenau Hospital
  - Wynnewood, Pennsylvania, United States, 19096
    - CCOP - Main Line Health
  - York, Pennsylvania, United States, 17405
    - York Cancer Center at Apple Hill Medical Center
- South Carolina
  - Anderson, South Carolina, United States, 29621
    - AnMed Cancer Center
  - Charleston, South Carolina, United States, 29425
    - Hollings Cancer Center at Medical University of South Carolina
  - Charleston, South Carolina, United States, 29401
    - Roper St. Francis Cancer Center at Roper Hospital
  - Greenville, South Carolina, United States, 29615
    - CCOP - Greenville
  - Spartanburg, South Carolina, United States, 29303
    - CCOP - Upstate Carolina
  - Spartanburg, South Carolina, United States, 29303
    - Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
- South Dakota
  - Sioux Falls, South Dakota, United States, 57105
    - Medical X-Ray Center, PC
  - Sioux Falls, South Dakota, United States, 57117-5039
    - Sanford Cancer Center at Sanford USD Medical Center
- Tennessee
  - Knoxville, Tennessee, United States, 37916
    - Thompson Cancer Survival Center
  - Memphis, Tennessee, United States, 38104
    - University of Tennessee Cancer Institute - Memphis
  - Nashville, Tennessee, United States, 37208-3599
    - MBCCOP - Meharry Medical College - Nashville
  - Nashville, Tennessee, United States, 37203
    - Nashville Oncology Associates, PC
- Texas
  - Laredo, Texas, United States, 78041
    - Doctor's Hospital of Laredo
  - San Antonio, Texas, United States, 78229-3900
    - University of Texas Health Science Center at San Antonio
- Utah
  - American Fork, Utah, United States, 84003
    - American Fork Hospital
  - Cedar City, Utah, United States, 84720
    - Sandra L. Maxwell Cancer Center
  - Murray, Utah, United States, 84157
    - Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
  - Ogden, Utah, United States, 84403
    - Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
  - Provo, Utah, United States, 84604
    - Utah Valley Regional Medical Center - Provo
  - Saint George, Utah, United States, 84770
    - Dixie Regional Medical Center - East Campus
  - Salt Lake City, Utah, United States, 84112
    - Huntsman Cancer Institute at University of Utah
  - Salt Lake City, Utah, United States, 84103
    - LDS Hospital
  - Salt Lake City, Utah, United States, 84106
    - Utah Cancer Specialists at UCS Cancer Center
- Vermont
  - Berlin Corners, Vermont, United States, 05602
    - Mountainview Medical
  - Burlington, Vermont, United States, 05401
    - Fletcher Allen Health Care - University Health Center Campus
- Virginia
  - Fredericksburg, Virginia, United States, 22401
    - Fredericksburg Oncology, Incorporated
  - Richmond, Virginia, United States, 23298-0037
    - Virginia Commonwealth University Massey Cancer Center
- Washington
  - Auburn, Washington, United States, 98002
    - Auburn Regional Center for Cancer Care
  - Centralia, Washington, United States, 98531-9027
    - Providence Centralia Hospital
  - Federal Way, Washington, United States, 98003
    - St. Francis Hospital
  - Olympia, Washington, United States, 98506-5166
    - Providence St. Peter Hospital Regional Cancer Center
  - Puyallup, Washington, United States, 98372
    - Good Samaritan Cancer Center
  - Tacoma, Washington, United States, 98405-3004
    - Franciscan Cancer Center at St. Joseph Medical Center
  - Tacoma, Washington, United States, 98405
    - Allenmore Hospital
  - Tacoma, Washington, United States, 98405
    - CCOP - Northwest
  - Tacoma, Washington, United States, 98405
    - MultiCare Regional Cancer Center at Tacoma General Hospital
  - Tacoma, Washington, United States, 98499
    - St. Clare Hospital
- West Virginia
  - Charleston, West Virginia, United States, 25304
    - West Virginia University Health Sciences Center - Charleston
  - Morgantown, West Virginia, United States, 26506
    - Mary Babb Randolph Cancer Center at West Virginia University Hospitals
  - Parkersburg, West Virginia, United States, 26102
    - Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital
- Wisconsin
  - Chippewa Falls, Wisconsin, United States, 54729
    - Marshfield Clinic - Chippewa Center
  - Eau Claire, Wisconsin, United States, 54701
    - Marshfield Clinic Cancer Care at Regional Cancer Center
  - Green Bay, Wisconsin, United States, 54311
    - Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical Center
  - La Crosse, Wisconsin, United States, 54601
    - Gundersen Lutheran Center for Cancer and Blood
  - Marshfield, Wisconsin, United States, 54449
    - Saint Joseph's Hospital
  - Marshfield, Wisconsin, United States, 54449
    - Marshfield Clinic - Marshfield Center
  - Milwaukee, Wisconsin, United States, 53226
    - Medical College of Wisconsin Cancer Center
  - Milwaukee, Wisconsin, United States, 53201-0342
    - Aurora Sinai Medical Center
  - Minocqua, Wisconsin, United States, 54548
    - Marshfield Clinic - Lakeland Center
  - Oshkosh, Wisconsin, United States, 54904
    - Vince Lombardi Cancer Clinic - Oshkosh
  - Rhinelander, Wisconsin, United States, 54501
    - Ministry Medical Group at Saint Mary's Hospital
  - Rice Lake, Wisconsin, United States, 54868
    - Marshfield Clinic - Indianhead Center
  - Stevens Point, Wisconsin, United States, 54481
    - Marshfield Clinic at Saint Michael's Hospital
  - Wausau, Wisconsin, United States, 54401
    - Marshfield Clinic - Wausau Center
  - West Allis, Wisconsin, United States, 53227
    - Aurora Women's Pavilion of West Allis Memorial Hospital
  - Weston, Wisconsin, United States, 54476
    - Marshfield Clinic - Weston Center
  - Wisconsin Rapids, Wisconsin, United States, 54494
    - Marshfield Clinic - Wisconsin Rapids Center
- Wyoming
  - Sheridan, Wyoming, United States, 82801
    - Welch Cancer Center at Sheridan Memorial Hospital

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 to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

Female

Description

Inclusion Criteria:

The patient must have consented to participate and must have signed and dated an appropriate Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines for the study treatment and submission of pre-entry core biopsy material for correlative studies.
Patients must be female.
Patients must be 18 years of age or older.
Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy.
The primary breast tumor must be palpable and measure greater than or equal to 2.0 cm on physical exam.
All patients must have their left ventricular ejection fraction (LVEF) assessed by multigated acquisition (MUGA) scan or echocardiogram within 3 months prior to study entry. The LVEF must be greater than or equal to the lower limit of normal (LLN) for the cardiac imaging facility performing the study. Note: If the cardiac imaging facility cannot provide a LLN, use 50% as the LLN value.
- Note: Since the pre-entry LVEF serves as the baseline for comparing subsequent LVEF assessments to determine if bevacizumab therapy can be continued, it is critical that this baseline study be an accurate assessment of the patient's LVEF. If the baseline LVEF is greater than 75%, the investigator should have the study reviewed for accuracy prior to study entry. Following study entry, the LVEF determination may be reviewed up until the time of the post-chemotherapy (preoperative) evaluation. Please note that if a more accurate value is obtained from the review of the baseline MUGA or echocardiogram, the correct value must be submitted to the NSABP before the post-chemotherapy (preoperative) MUGA or echocardiogram is performed or it cannot be used for managing postoperative bevacizumab.
All patients must have an EKG within 3 months prior to study entry.
At the time of randomization:
- Absolute neutrophil count (ANC) must be greater than or equal to 1200/mm3.
- Platelet count must be greater than or equal to 100,000/mm3.
- Hemoglobin must be greater than or equal to 10 g/dL.
- There must be evidence of adequate hepatic function by these criteria:
- Total bilirubin must be less than or equal to the ULN for the lab unless the patient has a grade 1 bilirubin elevation (greater than ULN to 1.5 x ULN) resulting from Gilbert's disease or similar syndrome due to slow conjugation of bilirubin; and
- Alkaline phosphatase must be less than or equal 2.5 x ULN for the lab; and
- Aspartate Aminotransferase (AST) must be less than or equal to 1.5 x ULN for the lab.
- Alkaline phosphatase and AST may not both be greater than the ULN. For example, if the alkaline phosphatase is greater than the ULN but less than or equal 2.5 x ULN, then the AST must be less than or equal the ULN. If the AST is greater than the ULN but less than or equal 1.5 x ULN, then the alkaline phosphatase must be less than or equal ULN.
Patients with either skeletal pain or alkaline phosphatase that is greater than ULN but less than or equal 2.5 x ULN are eligible for inclusion in the study if bone scans do not demonstrate metastatic disease. Suspicious findings on bone scan must be confirmed as benign by x-ray, MRI, or biopsy.
Patients with AST or alkaline phosphatase greater than ULN are eligible for inclusion in the study if liver imaging does not demonstrate metastatic disease and adequate bone marrow and liver function results as described above are met.
The following criteria for evidence of adequate renal function must be met:
Serum creatinine less than or equal ULN for the lab.
Calculated creatinine clearance must be greater than 50 mL/min.
Urine protein/urine creatinine (UPC) ratio must be less than 1.0.
Patient must be able to swallow oral medications.

Exclusion criteria:

Tumor determined to be strongly human epidermal growth factor receptor 2 (HER2)-positive by immunohistochemistry (3+) or by fluorescent in situ hybridization (positive for gene amplification).
Excisional or incisional biopsy for this primary breast tumor.
Surgical axillary staging procedure prior to study entry. Exceptions: 1) Fine Needle Aspiration (FNA) or core biopsy of an axillary node is permitted for any patient, and 2) although not recommended, a pre-neoadjuvant therapy sentinel lymph node biopsy for patients with clinically negative axillary nodes is permitted.
Tumors clinically staged as T4.
Ipsilateral cN2b or cN3 disease. (Patients with cN1 or cN2a disease are eligible.)
Definitive clinical or radiologic evidence of metastatic disease.
Synchronous bilateral breast cancer (invasive or DCIS).
Treatment including radiation therapy, chemotherapy, biotherapy, and/or hormonal therapy for the currently diagnosed breast cancer prior to study entry.
Any sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement therapy, etc. (These patients are eligible if this therapy is discontinued prior to randomization.)
Therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulator (SERM), either for osteoporosis or breast cancer prevention. (Patients are eligible only if these medications are discontinued prior to randomization.)
Prior history of breast cancer, including DCIS. (Patients with a history of lobular carcinoma in situ [LCIS] are eligible.)
Prior therapy with anthracyclines, taxanes, capecitabine, 5-FU (fluorouracil), gemcitabine, or bevacizumab for any malignancy.
Other malignancies unless the patient is considered to be disease-free for 5 or more years prior to randomization and is deemed by her physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
Cardiac disease that would preclude the use of anthracyclines. This includes:
- angina pectoris that requires the use of anti-anginal medication;
- history of documented congestive heart failure;
- serious cardiac arrhythmia requiring medication;
- severe conduction abnormality;
- valvular disease with documented cardiac function compromise; and
- uncontrolled hypertension defined as BP greater than 150/90 on antihypertensive therapy. (Patients with hypertension that is well controlled on medication are eligible.)
History of myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LV function.
History of transient ischemic attack (TIA) or cerebrovascular accident (CVA).
History of other arterial thrombotic event within 12 months before study entry.
Symptomatic peripheral vascular disease.
Any significant non-traumatic bleeding within 6 months before study entry.
Serious or non-healing wound, skin ulcers, or incompletely healed bone fracture.
Gastroduodenal ulcer(s) determined by endoscopy to be active.
Invasive procedures defined as follows:
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to planned start of study therapy. (Note: Placement of a vascular access device is not considered a major surgical procedure.)
- Anticipation of need for major surgical procedures (other than the required breast surgery) during the course of the study.
Known bleeding diathesis or coagulopathy. (Patients on warfarin with an in-range international normalized ratio [INR] [usually between 2 and 3] are eligible.)
Sensory/motor neuropathy greater than or equal grade 2, as defined by the NCI's Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v3.0).
Other non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude treatment with any of the treatment regimens or would prevent required follow-up.
Conditions that would prohibit administration of corticosteroids.
History of severe hypersensitivity reaction to drugs formulated with polysorbate 80.
Administration of any investigational agents within 30 days before study entry.
Pregnancy or lactation at the time of proposed randomization.

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)

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1A: Docetaxel then AC Patients receive docetaxel IV on day 1 every 3 weeks for up to 4 cycles. Patients then receive AC IV every 3 weeks for up to 4 cycles. Patients then undergo surgery (lumpectomy or mastectomy).	Drug: cyclophosphamide 600 mg/m2 IV Drug: docetaxel 100 mg/m2 IV Drug: doxorubicin hydrochloride (Adriamycin) 60 mg/m2 IV
Experimental: Arm 1B Docetaxel + Bev then AC + Bev Patients receive bevacizumab (bev) IV on day 1 and docetaxel every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab IV every 3 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Drug: cyclophosphamide 600 mg/m2 IV Drug: docetaxel 100 mg/m2 IV Drug: doxorubicin hydrochloride (Adriamycin) 60 mg/m2 IV Biological: bevacizumab 15 mg/kg IV
Experimental: Arm 2A: Docetaxel + Capecitabine then AC Patients receive docetaxel as in Arm 1A and oral capecitabine (cape) twice daily on days 1-14 every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A.	Drug: cyclophosphamide 600 mg/m2 IV Drug: docetaxel 100 mg/m2 IV Drug: doxorubicin hydrochloride (Adriamycin) 60 mg/m2 IV Drug: capecitabine 825 mg/m2 orally
Experimental: Arm 2B: Docetaxel + Cape + Bev then AC + Bev Patients receive bevacizumab as in Arm 1B and docetaxel and capecitabine as in Arm III. Treatment repeats every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1B. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B.	Drug: cyclophosphamide 600 mg/m2 IV Drug: docetaxel 100 mg/m2 IV Drug: doxorubicin hydrochloride (Adriamycin) 60 mg/m2 IV Biological: bevacizumab 15 mg/kg IV Drug: capecitabine 825 mg/m2 orally
Experimental: Arm 3A: Docetaxel + Gem then AC Patients receive docetaxel as in Arm 1A and gemcitabine hydrochloride IV on days 1 and 8 of each cycle every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A.	Drug: cyclophosphamide 600 mg/m2 IV Drug: docetaxel 100 mg/m2 IV Drug: doxorubicin hydrochloride (Adriamycin) 60 mg/m2 IV Drug: gemcitabine hydrochloride 1000 mg/m2 IV
Experimental: Arm 3B: Docetaxel + Gem + Bev then AC + Bev Patients receive docetaxel as in Arm 1A, gemcitabine hydrochloride as in Arm 3A, and bevacizumab as in Arm 1B. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B.	Drug: cyclophosphamide 600 mg/m2 IV Drug: docetaxel 100 mg/m2 IV Drug: doxorubicin hydrochloride (Adriamycin) 60 mg/m2 IV Biological: bevacizumab 15 mg/kg IV Drug: gemcitabine hydrochloride 1000 mg/m2 IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response (pCR) of the Primary Tumor in the Breast Time Frame: Time of surgery, on average 6 or 13 months	Percentage of patients absent of histologic evidence of invasive tumor cells in the surgical breast specimen.	Time of surgery, on average 6 or 13 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR in the Breast and Nodes Time Frame: Time of surgery, on average 6 or 13 months	Percentage of patients absent of histologic evidence of invasive tumor cells in the surgical breast specimen and axillary lymph nodes.	Time of surgery, on average 6 or 13 months
Clinical Overall Response (cOR) Following Docetaxel Alone, Docetaxel/Capecitabine, and Docetaxel/Gemcitabine Hydrochloride, With or Without Bevacizumab, as Assessed by Physical Exam at the Completion of the Docetaxel-based Portion of Chemotherapy Time Frame: Assessed at cycle 5 of chemotherapy, on average at 15 weeks	Percentages of patients assessed as Clinical Complete Response or Clinical Partial Response according to RECIST.	Assessed at cycle 5 of chemotherapy, on average at 15 weeks
Clinical Overall Response: cOR as Assessed by Physical Exam at the Completion of the Sequential Chemotherapy Regimens Time Frame: Three to four weeks after the last chemotherapy dose on average 6 or 13 months	The percentage of patients assessed by physical exam as Clinical Complete Response or Clinical Partial Response according to RECIST.	Three to four weeks after the last chemotherapy dose on average 6 or 13 months
Clinical Complete Response (cCR) Following Docetaxel Alone, Docetaxel/Capecitabine, and Docetaxel/Gemcitabine Hydrochloride, With or Without Bevacizumab, as Assessed by Physical Exam at Completion of Therapy Time Frame: Assessed at cycle 5 of chemotherapy, on average at 15 weeks	Percentages of patients assessed as Clinical Complete Response or Clinical Partial Response according to RECIST.	Assessed at cycle 5 of chemotherapy, on average at 15 weeks
Clinical Complete Resonse: cCR as Assessed by Physical Exam at the Completion of the Sequential Chemotherapy Regimens Time Frame: Three to four weeks after the last chemotherapy dose, on average at 6 or 13 months	The percentage of patients assessed by physical exam as Clinical Complete Response according to RECIST.	Three to four weeks after the last chemotherapy dose, on average at 6 or 13 months
Percentage of Cardiac Events Time Frame: After each cycle, 3-5 weeks postoperative, 9 and 12 months from study entry, every 6 month years 2-5, and annually years 6-10, for postoperative bevacizumab patients, every 6 weeks during postoperative therapy and at 18 months following study entry.		After each cycle, 3-5 weeks postoperative, 9 and 12 months from study entry, every 6 month years 2-5, and annually years 6-10, for postoperative bevacizumab patients, every 6 weeks during postoperative therapy and at 18 months following study entry.
Surgical Complication Time Frame: 24 months after study entry	Number of patients with Grade 4 or above surgery-related toxicities	24 months after study entry
Toxicities Including Events Other Than Congestive Heart Failure, of Chemotherapy Alone, Bevacizumab With Chemotherapy, and Bevacizumab Alone Time Frame: 24 months after study entry	The number of patients who experienced Grade 1 or above Adverse Events. Referring to the Adverse Events tables for specifics.	24 months after study entry
Disease-free Survival (DFS) Time Frame: Measured through 5 years after study enrollment	Percentage of patients free from local recurrence following mastectomy, local recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, contralateral breast cancer, second primary cancer after 5 years.	Measured through 5 years after study enrollment

Collaborators and Investigators

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

Sponsor

NSABP Foundation Inc

Collaborators

National Cancer Institute (NCI)

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

Bear HD, Tang G, Rastogi P, Geyer CE Jr, Robidoux A, Atkins JN, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012 Jan 26;366(4):310-20. doi: 10.1056/NEJMoa1111097.
Bear HD, Tang G, Rastogi P, et al.: The effect on pCR of bevacizumab and/or antimetabolites added to standard neoadjuvant chemotherapy: NSABP protocol B-40. [Abstract] J Clin Oncol 29 (Suppl 15): A-LBA1005, 2011.
Bear HD, Tang G, Rastogi P, Geyer CE Jr, Liu Q, Robidoux A, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Paik S, Swain SM, Mamounas EP, Wolmark N. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1037-1048. doi: 10.1016/S1470-2045(15)00041-8. Epub 2015 Aug 10. Erratum In: Lancet Oncol. 2015 Dec;16(16):e589.

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

November 1, 2006

Primary Completion (Actual)

March 1, 2011

Study Completion (Anticipated)

March 1, 2018

Study Registration Dates

First Submitted

December 6, 2006

First Submitted That Met QC Criteria

December 6, 2006

First Posted (Estimate)

December 7, 2006

Study Record Updates

Last Update Posted (Actual)

September 18, 2017

Last Update Submitted That Met QC Criteria

September 12, 2017

Last Verified

September 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

NSABP B-40

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.

Chemotherapy With or Without Bevacizumab in Treating Women With Stage I, Stage II, or Stage IIIA Breast Cancer That Can Be Removed By Surgery

Study Overview

Status

Conditions

Intervention / Treatment

Detailed Description

Study Type

Enrollment (Actual)

Phase

Contacts and Locations

Study Locations

Participation Criteria

Eligibility Criteria

Ages Eligible for Study

Accepts Healthy Volunteers

Genders Eligible for Study

Description

Study Plan

How is the study designed?

Design Details

Number of Arms

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Secondary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Collaborators and Investigators

Sponsor

Collaborators

Publications and helpful links

General Publications

Study record dates

Study Major Dates

Study Start

Primary Completion (Actual)

Study Completion (Anticipated)

Study Registration Dates

First Submitted

First Submitted That Met QC Criteria

First Posted (Estimate)

Study Record Updates

Last Update Posted (Actual)

Last Update Submitted That Met QC Criteria

Last Verified

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers