Four Versus Six Cycles of Cyclophosphamide/Doxorubicin or Paclitaxel in Adjuvant Breast Cancer

Cyclophosphamide And Doxorubicin (CA) (4 VS 6 Cycles) Versus Paclitaxel (4 VS 6 Cycles) As Adjuvant Therapy For Breast Cancer in Women With 0-3 Positive Axillary Lymph Nodes:A 2X2 Factorial Phase III Randomized Study

This randomized phase III trial studies cyclophosphamide and doxorubicin hydrochloride compared with paclitaxel as adjuvant therapy in treating breast cancer in women with 0-3 positive axillary lymph nodes. Giving additional cancer treatment after surgery may help to lower the risk that the cancer will come back (adjuvant therapy). Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether the standard adjuvant therapy of cyclophosphamide and doxorubicin hydrochloride is more effective than paclitaxel in treating women with breast cancer

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: paclitaxel; Drug: AC regimen

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the equivalence of paclitaxel given every two weeks with cyclophosphamide and doxorubicin hydrochloride (CA) given every two weeks as adjuvant therapy for women with 0-3 positive axillary lymph nodes, for disease-free survival.

II. To determine if longer therapy, 12 weeks, is superior to shorter therapy, 8 weeks, of either CA or paclitaxel for disease-free survival for women with primary breast cancer with 0-3 positive axillary lymph nodes.

SECONDARY OBJECTIVES:

I. To determine the equivalence of paclitaxel given every two weeks with CA given every two weeks, and the potential superiority of longer vs. shorter therapy, in relation to overall survival, local control (regardless of metastatic status) and time to distant metastases (regardless of local recurrence status).

II. To compare toxicities of short and long course CA and paclitaxel as adjuvant therapy for women with 0-3 positive axillary lymph node breast cancer.

III. To determine the effect of long and short course CA and paclitaxel on the induction of menopause for pre-menopausal patients.

IV. To assess the discrepancy of myelosuppression among the common multidrug resistance protein 1 (MDR1) haplotypes in the CA treatment arm.

V. To assess the effect of MDR1 haplotypes on disease-free survival (DFS) adjusted for treatment.

VI. Exploratory analysis of the effect of cytochrome P450, family 3, subfamily A, polypeptide 5 (CYP3A5), cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8), and cytochrome P450, family 2, subfamily B, polypeptide 6 (CYP2B6) polymorphisms on DFS and toxicity.

VII. To identify genetic markers associated with the risk of developing neutropenia in adriamycin/ cyclophosphamide-treated breast cancer patients.

VIII. To identify genetic markers associated with the risk of developing peripheral neuropathy in paclitaxel-treated breast cancer patients.

IX. To identify genetic markers associated with differences in the efficacy of each chemotherapy regimen.

X. To examine genetic associations with other response and toxicity phenotypes that become apparent during future analysis of Cancer and Leukemia Group B (CALGB) 40101 data.

XI. To identify copy number variants associated with adriamycin/cyclophosphamide-induced neutropenia and paclitaxel-induced peripheral neuropathy.

OUTLINE: Patients are randomized to 1 of 4 treatment arms.

ARM I: Patients receive cyclophosphamide intravenously (IV) and doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.

ARM III: Patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.

ARM IV: Patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Note: Randomization to Arms II and IV is no longer available, effective 12/15/2007.

After completion of study treatment patients are followed up for 4-6 weeks, every 6 months for 2 years, and then annually for up to 13 years.

• Study Type: Interventional
• Enrollment (Actual): 3871
• Phase: Phase 3

Contacts and Locations

Study Locations

• South Africa
  • Pretoria, South Africa, 0002
    • Pretoria Academic Hospital
• United States
  • Alabama
    • Anniston, Alabama, United States, 36202
      • Regional Medical Center
    • Birmingham, Alabama, United States, 35294
      • UAB Comprehensive Cancer Center
    • Mobile, Alabama, United States, 36608
      • Providence Cancer Center at Providence Hospital
  • Alaska
    • Fairbanks, Alaska, United States, 99701
      • Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5499
      • Mayo Clinic Scottsdale
  • Arkansas
    • Ft. Smith, Arkansas, United States, 72903
      • Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
  • California
    • Berkeley, California, United States, 94704
      • Alta Bates Summit Comprehensive Cancer Center
    • Burlingame, California, United States, 94010
      • Peninsula 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
    • Fremont, California, United States, 94538
      • Valley Medical Oncology
    • Fremont, California, United States, 94538
      • Washington Township Hospital
    • Fresno, California, United States, 93720
      • Cancer Care Associates
    • Fresno, California, United States, 93720
      • California Cancer Center - Woodward Park Office
    • Greenbrae, California, United States, 94904
      • Marin Cancer Institute at Marin General Hospital
    • La Jolla, California, United States, 92093-0658
      • Rebecca and John Moores UCSD Cancer Center
    • Los Angeles, California, United States, 90089-9181
      • USC/Norris Comprehensive Cancer Center and Hospital
    • Martinez, California, United States, 94553-3156
      • Contra Costa Regional Medical Center
    • Marysville, California, United States, 95901
      • Tibotec Therapeutics - Division of Ortho Biotech Products, LP
    • Modesto, California, United States, 95355
      • Memorial Medical 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
      • CCOP - Bay Area Tumor Institute
    • Oakland, California, United States, 94609
      • Bay Area Breast Surgeons, Incorporated
    • Oakland, California, United States, 94609
      • Tom K Lee, Incorporated
    • Pleasanton, California, United States, 94588
      • Valley Care Medical Center
    • Pleasanton, California, United States, 94588
      • Valley Medical Oncology Consultants - Pleasanton
    • Redding, California, United States, 96049
      • Mercy Regional Cancer Center at Mercy Medical Center
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
    • San Diego, California, United States, 92134
      • Naval Medical Center - San Diego
    • San Francisco, California, United States, 94118
      • California Pacific Medical Center - California Campus
    • San Pablo, California, United States, 94806
      • Doctors Medical Center - San Pablo Campus
    • San Rafael, California, United States, 94903
      • Sutter Health - Western Division Cancer Research Group
    • Truckee, California, United States, 96161
      • Tahoe Forest Cancer Center
  • 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
    • 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
    • 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
    • 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, District of Columbia, United States, 20016
      • Sibley Memorial Hospital
    • Washington, District of Columbia, United States, 20307-5001
      • Walter Reed Army Medical Center
  • Florida
    • Daytona Beach, Florida, United States, 32114
      • Herbert D. Kerman Regional Oncology Center - Daytona Beach
    • Fort Lauderdale, Florida, United States, 33308
      • Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
    • Gainesville, Florida, United States, 32610-0232
      • University of Florida Shands Cancer Center
    • Hollywood, Florida, United States, 33021
      • Memorial Cancer Institute at Memorial Regional Hospital
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
    • Jupiter, Florida, United States, 33458
      • Ella Milbank Foshay Cancer Center at Jupiter Medical Center
    • Lakeland, Florida, United States, 33805
      • Lakeland Regional Cancer Center at Lakeland Regional Medical Center
    • Lakeland, Florida, United States, 33805
      • Center for Cancer Care and Research at Watson Clinic, LLP
    • Miami Beach, Florida, United States, 33140
      • CCOP - Mount Sinai Medical Center
    • Orange Park, Florida, United States, 32073
      • Integrated Community Oncology Network - Orange Park
    • Orlando, Florida, United States, 32803-1273
      • Florida Hospital Cancer Institute at Florida Hospital Orlando
    • West Palm Beach, Florida, United States, 33401
      • Palm Beach Cancer Institute - West Palm Beach
  • Georgia
    • Columbus, Georgia, United States, 31904
      • John B. Amos Cancer Center
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center
    • Macon, Georgia, United States, 31208
      • Medical Center of Central Georgia
    • 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
  • Idaho
    • Boise, Idaho, United States, 83712
      • Mountain States Tumor Institute at St. Luke's Regional Medical Center
  • Illinois
    • Alton, Illinois, United States, 62002
      • Saint Anthony's Hospital at Saint Anthony's Health Center
    • Aurora, Illinois, United States, 60504
      • Rush-Copley Cancer Care Center
    • Chicago, Illinois, United States, 60611-3013
      • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
    • Chicago, Illinois, United States, 60612-7243
      • University of Illinois Cancer Center
    • Chicago, Illinois, United States, 60608
      • Mount Sinai Hospital Medical Center
    • Chicago, Illinois, United States, 60625
      • Swedish Covenant Hospital
    • Chicago, Illinois, United States, 60611
      • Hematology and Oncology Associates
    • Chicago, Illinois, United States, 60657
      • Creticos Cancer Center at Advocate Illinois Masonic Medical Center
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital Cancer Care Institute
    • Elk Grove Village, Illinois, United States, 60007
      • Alexian Brothers Radiation Oncology
    • Evanston, Illinois, United States, 60202
      • St. Francis Hospital
    • Harvey, Illinois, United States, 60426
      • Ingalls Cancer Care Center at Ingalls Memorial Hospital
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology-Hematology Associates, Limited - West
    • Joliet, Illinois, United States, 60432
      • Midwest Center for Hematology/Oncology
    • Kankakee, Illinois, United States, 60901
      • Provena St. Mary's Regional Cancer Center - Kankakee
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
    • Moline, Illinois, United States, 61265
      • Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
    • Mt. Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
    • Olympia Fields, Illinois, United States, 60461
      • Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields
    • Park Ridge, Illinois, United States, 60068-1174
      • Advocate Lutheran General Cancer Care Center
    • Rockford, Illinois, United States, 61104-2315
      • Swedish-American Regional Cancer Center
    • Rockford, Illinois, United States, 61108
      • Center for Cancer Care at OSF Saint Anthony Medical Center
    • Springfield, Illinois, United States, 62781-0001
      • Regional Cancer Center at Memorial Medical Center
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center at Carle Foundation Hospital
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer 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
    • Kokomo, Indiana, United States, 46904
      • Howard Community Hospital
    • La Porte, Indiana, United States, 46350
      • Center for Cancer Therapy at LaPorte Hospital and Health Services
    • Michigan City, Indiana, United States, 46360
      • Saint Anthony Memorial Health Centers
    • 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
    • Bettendorf, Iowa, United States, 52722
      • Hematology Oncology Associates of the Quad Cities
    • Cedar Rapids, Iowa, United States, 52402
      • St. Luke's Hospital
    • Cedar Rapids, Iowa, United States, 52403
      • Cedar Rapids Oncology Associates
    • Cedar Rapids, Iowa, United States, 52403
      • Mercy Regional Cancer Center at Mercy Medical Center
    • Cedar Rapids, Iowa, United States, 52402
      • Iowa Blood and Cancer Care
    • Council Bluffs, Iowa, United States, 51503
      • Heartland Oncology and Hematology
    • Davenport, Iowa, United States, 52803
      • Genesis Regional Cancer Center at Genesis Medical Center
    • Des Moines, Iowa, United States, 50309
      • CCOP - Iowa Oncology Research Association
    • Des Moines, Iowa, United States, 50309
      • John Stoddard Cancer Center at Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates at John Stoddard Cancer Center
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates at Mercy Cancer Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Cancer Center at Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50316
      • John Stoddard Cancer Center at Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50307
      • Mercy Capitol Hospital
    • 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
    • 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
    • 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 Mission, Kansas, United States, 66204
      • Shawnee Mission Medical Center
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Cancer Center
    • Topeka, Kansas, United States, 66606
      • St. Francis Comprehensive Cancer Center
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas, PA - Wellington
    • 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
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Mary Bird Perkins Cancer Center - Baton Rouge
    • Baton Rouge, Louisiana, United States, 70809
      • Ochsner Health Center - Bluebonnet
    • Baton Rouge, Louisiana, United States, 70806
      • Pennington Cancer Center at Baton Rouge General
    • Covington, Louisiana, United States, 70433
      • Ochsner Health Center - Covington
    • 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
    • Augusta, Maine, United States, 04330
      • Harold Alfond Center for Cancer Care
    • Bangor, Maine, United States, 04401
      • CancerCare of Maine at Eastern Maine Medical Center
    • Scarborough, Maine, United States, 04074
      • Maine Center for Cancer Medicine and Blood Disorders - Scarborough
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Baltimore, Maryland, United States, 21201
      • Greenebaum Cancer Center at University of Maryland Medical Center
    • Elkton MD, Maryland, United States, 21921
      • Union Hospital Cancer Program at Union Hospital
    • Frederick, Maryland, United States, 21701
      • Frederick Memorial Hospital Regional Cancer Therapy Center
    • Salisbury, Maryland, United States, 21801
      • Peninsula Regional Medical Center
  • Massachusetts
    • Attleboro, Massachusetts, United States, 02703
      • Sturdy Memorial Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Brigham and Women's Cancer Center
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
    • Brighton, Massachusetts, United States, 02135-2997
      • Caritas St. Elizabeth's Medical Center
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic Medical Center - Burlington
    • Fall River, Massachusetts, United States, 02721
      • Hudner Oncology Center at Saint Anne's Hospital - Fall River
    • Gloucester, Massachusetts, United States, 01930
      • Addison Gilbert Hospital
    • Hyannis, Massachusetts, United States, 02601
      • Cape Cod Hospital
    • Lowell, Massachusetts, United States, 01854
      • Lowell General Hospital
    • Norwood, Massachusetts, United States, 02062
      • Caritas Norwood Hospital
    • Peabody, Massachusetts, United States, 01960
      • NSMC Cancer Center - Peabody
    • Pittsfield, Massachusetts, United States, 01201
      • Berkshire Hematology Oncology, PC
    • Westfield, Massachusetts, United States, 01085
      • Noble Hospital
    • Worcester, Massachusetts, United States, 01655
      • UMASS Memorial Cancer Center - University Campus
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center at Bixby Medical Center
    • Ann Arbor, Michigan, United States, 48109-0942
      • University of Michigan Comprehensive Cancer 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, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • 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
    • 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
    • Petoskey, Michigan, United States, 49770
      • Northern Michigan Hospital
    • Pontiac, Michigan, United States, 48341-2985
      • St. Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Mercy Regional Cancer Center at Mercy Hospital
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital - Royal Oak Campus
    • Saginaw, Michigan, United States, 48601
      • Seton Cancer Institute at Saint Mary's - Saginaw
    • Saint Joseph, Michigan, United States, 49085
      • Lakeside Cancer Specialists, PLLC
    • St. Joseph, Michigan, United States, 49085
      • Lakeland Regional Cancer Care Center - St. Joseph
    • Warren, Michigan, United States, 48093
      • St. John Macomb Hospital
  • Minnesota
    • Bemidji, Minnesota, United States, 56601
      • MeritCare Bemidji
    • 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
    • Duluth, Minnesota, United States, 55805
      • St. Luke's Hospital Cancer Care Center
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fergus Falls, Minnesota, United States, 56537
      • Fergus Falls Medical Group, PA
    • Fridley, Minnesota, United States, 55432
      • Mercy and Unity Cancer Center at Unity Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Mankato, Minnesota, United States, 56002
      • Immanuel St. Joseph's
    • 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, 55455
      • Masonic Cancer Center at University of Minnesota
    • 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
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
    • Saint Cloud, Minnesota, United States, 56303
      • CentraCare Clinic - River Campus
    • 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
    • Shakopee, Minnesota, United States, 55379
      • St. Francis Cancer Center at St. Francis Medical Center
    • St. Paul, Minnesota, United States, 55101
      • Regions Hospital Cancer Care 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
    • Hattiesburg, Mississippi, United States, 39402
      • Hematology & Oncology Clinic
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Cancer Clinic
    • Pascagoula, Mississippi, United States, 39581
      • Regional Cancer Center at Singing River Hospital
  • Missouri
    • Branson, Missouri, United States, 65616
      • Skaggs Cancer Center at Skaggs Regional Medical Center
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Chesterfield, Missouri, United States, 63017
      • Saint Luke's Hospital
    • 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
    • Saint Joseph, Missouri, United States, 64506
      • Heartland Regional Medical Center
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Cancer Center
    • Saint Louis, Missouri, United States, 63141
      • CCOP - St. Louis-Cape Girardeau
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
    • Saint Louis, Missouri, United States, 63141
      • Arch Medical Services, Incorporated at Center for Cancer Care and Research
    • 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
      • Sletten Cancer Institute at Benefis Healthcare
    • Helena, Montana, United States, 59601
      • St. Peter's Hospital
    • 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, 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
    • Grand Island, Nebraska, United States, 68803
      • Saint Francis Cancer Treatment Center at Saint Francis Memorial Health Center
    • Kearney, Nebraska, United States, 68848-1990
      • Good Samaritan Cancer Center at Good Samaritan Hospital
    • Lincoln, Nebraska, United States, 68510
      • Cancer Resource Center - Lincoln
    • North Platte, Nebraska, United States, 69103
      • Callahan Cancer Center at Great Plains Regional Medical Center
    • Omaha, Nebraska, United States, 68198-6805
      • UNMC Eppley Cancer Center at the University of Nebraska Medical Center
    • 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
    • Omaha, Nebraska, United States, 68114
      • Methodist Estabrook Cancer Center
    • Omaha, Nebraska, United States, 68106
      • CCOP Missouri Valley Cancer Consortium
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Nevada Cancer Research Foundation
  • New Hampshire
    • Concord, New Hampshire, United States, 03301
      • New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
    • Exeter, New Hampshire, United States, 03833
      • Center for Cancer Care at Exeter Hospital
    • Hooksett, New Hampshire, United States, 03106
      • New Hampshire Oncology - Hematology, PA - Hooksett
    • Keene, New Hampshire, United States, 03431
      • Kingsbury Center for Cancer Care at Cheshire Medical Center
    • Laconia, New Hampshire, United States, 03246
      • Lakes Region General Hospital
    • Lebanon, New Hampshire, United States, 03756-0002
      • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
    • Londonderry, New Hampshire, United States, 03053
      • Dana-Farber Cancer Institute at Londonderry
    • Manchester, New Hampshire, United States, 03103
      • Elliot Regional Cancer Center at Elliot Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • CCOP - Northern New Jersey
    • Morristown, New Jersey, United States, 07962
      • Carol G. Simon Cancer Center at Morristown Memorial Hospital
    • Newark, New Jersey, United States, 07103
      • UMDNJ University Hospital
    • Somerville, New Jersey, United States, 08876
      • Somerset Medical Center
    • Summit, New Jersey, United States, 07902
      • Overlook Hospital
    • Vineland, New Jersey, United States, 08360
      • Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
    • Voorhees, New Jersey, United States, 08043
      • Cancer Institute of New Jersey at Cooper - Voorhees
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein Cancer Center at Albert Einstein College of Medicine
    • Bronx, New York, United States, 10466
      • Our Lady of Mercy Medical Center Comprehensive Cancer Center
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • East Syracuse, New York, United States, 13057
      • CCOP - Hematology-Oncology Associates of Central New York
    • Elmhurst, New York, United States, 11373
      • Elmhurst Hospital Center
    • Jamaica, New York, United States, 11432
      • Queens Cancer Center of Queens Hospital
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
    • Plattsburgh, New York, United States, 12901
      • Fitzpatrick Cancer Center at Champlain Valley Physicians Hospital Medical Center
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • Rochester, New York, United States, 14620
      • Highland Hospital of Rochester
    • Rochester, New York, United States, 14621
      • Lipson Cancer and Blood Center at Rochester General Hospital
    • Stony Brook, New York, United States, 11794-9446
      • Stony Brook University Cancer Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Hospital
    • Utica, New York, United States, 13502
      • Faxton Regional Cancer Center
  • North Carolina
    • Asheboro, North Carolina, United States, 27203-5400
      • Randolph Hospital
    • Burlington, North Carolina, United States, 27216
      • Alamance Cancer Center at Alamance Regional Medical Center
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
    • Concord, North Carolina, United States, 28025
      • Batte Cancer Center at Northeast Medical Center
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
    • Fayetteville, North Carolina, United States, 28302-2000
      • Cape Fear Valley Medical Center Cancer 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
    • Greenville, North Carolina, United States, 27834
      • Leo W. Jenkins Cancer Center at ECU Medical School
    • Henderson, North Carolina, United States, 27536
      • Maria Parham Medical Center
    • Hendersonville, North Carolina, United States, 28791
      • Pardee Memorial Hospital
    • Kinston, North Carolina, United States, 28501
      • Kinston Medical Specialists
    • Lumberton, North Carolina, United States, 28359
      • Southeastern Regional Medical Center
    • Oxford, North Carolina, United States, 27565
      • Granville Medical Center
    • Raleigh, North Carolina, United States, 27609
      • Duke Health Raleigh Hospital
    • Reidsville, North Carolina, United States, 27320
      • Annie Penn Cancer Center
    • Roxboro, North Carolina, United States, 27573
      • Person Memorial 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
    • Wilmington, North Carolina, United States, 28401
      • Zimmer Cancer Center at New Hanover Regional Medical Center
    • Winston-Salem, North Carolina, United States, 27157-1096
      • Wake Forest University Comprehensive Cancer Center
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Bismarck Cancer Center
    • Bismarck, North Dakota, United States, 58501
      • Medcenter One Hospital Cancer Care Center
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic, PC
    • Bismarck, North Dakota, United States, 58502
      • St. Alexius Medical Center Cancer Center
    • Fargo, North Dakota, United States, 58122
      • CCOP - MeritCare Hospital
    • Fargo, North Dakota, United States, 58122
      • MeritCare Broadway
    • Grand Forks, North Dakota, United States, 58201
      • Altru Cancer Center at Altru Hospital
    • Minot, North Dakota, United States, 58701
      • Trinity Cancercare Center
  • Ohio
    • 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
    • Canton, Ohio, United States, 44708
      • Mercy Cancer Center at Mercy Medical Center
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Cleveland, Ohio, United States, 44106-5065
      • Case Comprehensive Cancer Center
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Cancer Care Center at MetroHealth Medical Center
    • Clyde, Ohio, United States, 43410
      • North Coast Cancer Care - Clyde
    • Columbus, Ohio, United States, 43214-3998
      • Riverside Methodist Hospital Cancer Care
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health - West Hospital
    • Columbus, Ohio, United States, 43215
      • CCOP - Columbus
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center Cancer Care
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital at Ohio Health
    • 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
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • 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
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Lima, Ohio, United States, 45804
      • Lima Memorial Hospital
    • Lima, Ohio, United States, 45801
      • St. Rita's Medical Center
    • Marietta, Ohio, United States, 45750
      • Strecker Cancer Center at Marietta Memorial Hospital
    • Maumee, Ohio, United States, 43537
      • St. Luke's Hospital
    • Maumee, Ohio, United States, 43537-1839
      • Northwest Ohio Oncology Center
    • Newark, Ohio, United States, 43055
      • Licking Memorial Cancer Care Program at Licking Memorial Hospital
    • 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
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care, Incorporated
    • Springfield, Ohio, United States, 45505
      • Community Hospital of Springfield and Clark County
    • Springfield, Ohio, United States, 45504
      • Mercy Medical Center
    • 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
    • Westerville, Ohio, United States, 43081
      • Mount Carmel St. Ann's Cancer Center
    • Wilmington, Ohio, United States, 45177
      • Clinton Memorial Hospital
    • Wooster, Ohio, United States, 44691
      • Cleveland Clinic - Wooster
    • Wright-Patterson Afb, Ohio, United States, 45433-5529
      • United States Air Force Medical Center - Wright-Patterson
    • 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
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Cancer Institute
    • Oklahoma City, Oklahoma, United States, 73120
      • Cancer Care Associates - Mercy Campus
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center at St. Francis Hospital
  • Oregon
    • Grants Pass, Oregon, United States, 97527
      • Three Rivers Community Hospital
    • Gresham, Oregon, United States, 97030
      • Legacy Mount Hood Medical Center
    • Medford, Oregon, United States, 97504
      • Dubs Cancer Center at Rogue Valley Medical Center
    • Medford, Oregon, United States, 97504
      • Providence Cancer Center at PMCC
    • Milwaukie, Oregon, United States, 97222
      • Providence Milwaukie Hospital
    • Portland, Oregon, United States, 97216
      • Adventist Medical Center
    • Portland, Oregon, United States, 97210
      • Legacy Good Samaritan Hospital & Comprehensive Cancer Center
    • Portland, Oregon, United States, 97213-2967
      • Providence Cancer Center at Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • CCOP - Columbia River Oncology Program
    • Portland, Oregon, United States, 97225
      • Providence St. Vincent Medical Center
    • Portland, Oregon, United States, 97227
      • Legacy Emanuel Hospital and Health Center and Children's Hospital
    • Portland, Oregon, United States, 97232
      • Kaiser Permanente Health Care - Portland
    • Tualatin, Oregon, United States, 97062
      • Legacy Meridian Park Hospital
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Cancer Institute at Milton S. Hershey Medical Center
    • Lancaster, Pennsylvania, United States, 17604
      • Lancaster General Hospital
    • Lewistown, Pennsylvania, United States, 17044
      • Lewistown Hospital
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Fox Chase Cancer Center - Philadelphia
    • Philadelphia, Pennsylvania, United States, 19107-5541
      • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
    • Philadelphia, Pennsylvania, United States, 19107
      • Joan Karnell Cancer Center at Pennsylvania Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Cancer Centers
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Cancer Center at Allegheny General Hospital
    • Reading, Pennsylvania, United States, 19605
      • St. Joseph Medical Center
    • Scranton, Pennsylvania, United States, 18501
      • Mercy Hospital Cancer Center - Scranton
    • Scranton, Pennsylvania, United States, 18510
      • Hematology and Oncology Associates of Northeastern Pennsylvania
    • Sellersville, Pennsylvania, United States, 18960
      • Grand View Hospital
    • State College, Pennsylvania, United States, 16803
      • Mount Nittany Medical Center
  • Rhode Island
    • Pawtucket, Rhode Island, United States, 02860
      • Memorial Hospital of Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Miriam Hospital
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital Comprehensive Cancer Center
    • Warwick, Rhode Island, United States, 02886
      • Kent County Memorial Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Roper St. Francis Cancer Center at Roper Hospital
    • Columbia, South Carolina, United States, 29203
      • Palmetto Health South Carolina Cancer Center
    • Florence, South Carolina, United States, 29501
      • McLeod Regional Medical Center
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
  • South Dakota
    • Aberdeen, South Dakota, United States, 57401
      • Oncology Services of Aberdeen
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
    • 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
    • Nashville, Tennessee, United States, 37208-3599
      • MBCCOP - Meharry Medical College - Nashville
    • Nashville, Tennessee, United States, 37203
      • Nashville Oncology Associates, PC
  • Texas
    • Amarillo, Texas, United States, 79106
      • Harrington Cancer Center
    • Dallas, Texas, United States, 75390
      • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
  • Virginia
    • Charlottesville, Virginia, United States, 22901
      • Martha Jefferson Hospital Cancer Care Center
    • Fredericksburg, Virginia, United States, 22401
      • Fredericksburg Oncology, Incorporated
    • Hampton, Virginia, United States, 23666
      • Virginia Oncology Associates - Hampton
    • Lynchburg, Virginia, United States, 24501
      • Lynchburg Hematology-Oncology Clinic
    • Richmond, Virginia, United States, 23230
      • Virginia Cancer Institute - West End
    • Roanoke, Virginia, United States, 24014
      • Carilion Cancer Center of Western Virginia
  • Washington
    • Auburn, Washington, United States, 98002
      • Auburn Regional Center for Cancer Care
    • Bellingham, Washington, United States, 98225
      • St. Joseph Cancer Center
    • Bremerton, Washington, United States, 98310
      • Olympic Hematology and Oncology
    • Centralia, Washington, United States, 98531-9027
      • Providence Centralia Hospital
    • Federal Way, Washington, United States, 98003
      • St. Francis Hospital
    • Kennewick, Washington, United States, 99336
      • Columbia Basin Hematology
    • Kirkland, Washington, United States, 98033
      • Cascade Cancer Center at Evergreen Hospital Medical Center
    • Mt. Vernon, Washington, United States, 98273
      • Skagit Valley Hospital Cancer Care Center
    • Olympia, Washington, United States, 98506-5166
      • Providence St. Peter Hospital Regional Cancer Center
    • Poulsbo, Washington, United States, 98370
      • Harrison Poulsbo Hematology and Onocology
    • Puyallup, Washington, United States, 98372
      • Good Samaritan Cancer Center
    • Renton, Washington, United States, 98055
      • Valley Medical Center
    • Seattle, Washington, United States, 98101
      • CCOP - Virginia Mason Research Center
    • Seattle, Washington, United States, 98104
      • Minor and James Medical, PLLC
    • Seattle, Washington, United States, 98112
      • Group Health Central Hospital
    • Seattle, Washington, United States, 98122-4307
      • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
    • Seattle, Washington, United States, 98122
      • Polyclinic First Hill
    • Seattle, Washington, United States, 98195
      • University Cancer Center at University of Washington Medical Center
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Spokane, Washington, United States, 99218
      • Evergreen Hematology and Oncology, PS
    • Spokane, Washington, United States, 99204-2967
      • Rockwood Clinic Cancer Treatment Center
    • Spokane, Washington, United States, 99204
      • Providence Cancer Center at Sacred Heart Medical Center
    • Spokane, Washington, United States, 99207
      • Providence Cancer Center at Holy Family Hospital
    • 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
    • Tacoma, Washington, United States, 98431
      • Madigan Army Medical Center - Tacoma
    • Vancouver, Washington, United States, 98668
      • Southwest Washington Medical Center Cancer Center
    • Wenatchee, Washington, United States, 98801-2028
      • Wenatchee Valley Medical Center
    • Yakima, Washington, United States, 98902
      • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • Edwards Comprehensive Cancer Center at Cabell Huntington 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
    • Eau Claire, Wisconsin, United States, 54703-1510
      • Midelfort Clinic - Luther
    • Eau Claire, Wisconsin, United States, 54702
      • Luther Midlelfort Hospital
    • Elkhorn, Wisconsin, United States, 53121
      • Vince Lombardi Cancer Center at Aurora Lakeland Medical Center - Elkhorn
    • Green Bay, Wisconsin, United States, 54311
      • Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical Center
    • Janesville, Wisconsin, United States, 53547
      • Mercy Regional Cancer Center
    • Johnson Creek, Wisconsin, United States, 53038
      • UW Cancer Center Johnson Creek
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Center for Cancer and Blood
    • La Crosse, Wisconsin, United States, 54601
      • Franciscan Skemp Healthcare - La Crosse Campus
    • Madison, Wisconsin, United States, 53792-6164
      • University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
    • Madison, Wisconsin, United States, 53717
      • Dean Medical Center - Madison
    • Manitowoc, Wisconsin, United States, 54221-1450
      • Holy Family Memorial Medical Center Cancer Care Center
    • Marinette, Wisconsin, United States, 54143
      • Vince Lombardi Cancer Clinic - Marinette
    • Marshfield, Wisconsin, United States, 54449
      • Saint Joseph's Hospital
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic - Marshfield Center
    • Mequon, Wisconsin, United States, 53097
      • Columbia Saint Mary's Hospital - Ozaukee
    • Milwaukee, Wisconsin, United States, 53201-0342
      • Aurora Sinai Medical Center
    • Milwaukee, Wisconsin, United States, 53215
      • Medical Consultants, Limited
    • Milwaukee, Wisconsin, United States, 53211
      • Columbia-Saint Mary's Cancer Care Center
    • Minocqua, Wisconsin, United States, 54548
      • Marshfield Clinic - Lakeland Center
    • Oconomowoc, Wisconsin, United States, 53066
      • Regional Cancer Center at Oconomowoc Memorial Hospital
    • Rhinelander, Wisconsin, United States, 54501
      • Ministry Medical Group at Saint Mary's Hospital
    • Rice Lake, Wisconsin, United States, 54868
      • Marshfield Clinic - Indianhead Center
    • Sheboygan, Wisconsin, United States, 53081
      • Vince Lombardi Cancer Clinic - Sheboygan
    • Stevens Point, Wisconsin, United States, 54481
      • Saint Michael's Hospital Cancer Center
    • Summit, Wisconsin, United States, 53066
      • Aurora Medical Center
    • Two Rivers, Wisconsin, United States, 54241
      • Vince Lombardi Cancer Clinic - Two Rivers
    • Waukesha, Wisconsin, United States, 53188
      • Waukesha Memorial Hospital Regional Cancer Center
    • Wausau, Wisconsin, United States, 54401
      • Marshfield Clinic - Wausau 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

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Eligibility Criteria:

• Patients must have histologically confirmed invasive carcinoma of the female breast, with 0-3 positive axillary lymph nodes
• Patients must have 0-3 positive axillary lymph nodes to be eligible for this study; patients with node-negative breast cancer should have sufficiently "high risk" disease to warrant chemotherapy; as general guidelines, node-negative patients with tumors of >= 1 cm or estrogen or progesterone receptor negative tumors of any size may be eligible; ultimately though, the definition of "high risk" may be determined by the treating physician, and if the treating physician feels the patient warrants chemotherapy, the patient is eligible; for patients with 1-3 positive axillary nodes, the patient is eligible regardless of primary breast tumor characteristics, if in the opinion of the treating physician, chemotherapy is deemed potentially beneficial to the patient
• If the patient has had a negative sentinel node biopsy, then no further axillary dissection is required, and the patient is determined to be node-negative; if an axillary dissection, without a sentinel node biopsy, is performed to determine nodal status, at least six axillary lymph nodes must be removed and analyzed and negative for the patient to be considered node-negative; axillary nodes with single cells or tumor clusters =< 0.2 mm by either hematoxylin and eosin stain (H&E) or immunohistochemistry (IHC), will be considered node-negative; lymph nodes positive for polymerase chain reaction (PCR) with tumor cells/clusters =< 0.2 mm will be considered node-negative; any axillary lymph node with tumor clusters > 0.2 mm will be considered positive
• If the patient has a sentinel node biopsy and one of the sentinel nodes is positive, as defined by tumor clusters > 0.2 mm, an axillary dissection must be performed; a total of at least 6 axillary lymph nodes, including sentinel nodes plus the subsequent dissection, must be removed for the patient to be eligible; of all the lymph nodes removed from both the sentinel node procedure and the axillary dissection, 1-3 must be positive for the patient to be eligible as a node-positive patient; if an axillary dissection is done without a sentinel node procedure, at least 6 lymph nodes must be removed and a 1-3 nodes must be positive for the patient to be considered node-positive and eligible for this study
• Determination of involvement of axillary nodes with metastatic cancer will follow the revised tumor-node-metastasis (TNM) staging system: axillary nodes with single cells with tumor clusters =< 0.2 mm, by either H&E or immunohistochemistry (IHC), will be considered negative axillary node; lymph nodes positive for PCR with tumor cells/clusters < 0.2 mm will be considered negative axillary node; any axillary lymph node with clusters > 0.2 mm will be considered to be positive
• Patients with estrogen-receptor and/or progesterone receptor negative, positive, or unknown tumors are eligible; estrogen-receptor (ER) and progesterone receptor (PgR) assays should be performed by immunohistochemical methods according to the local institution's standard protocol
• Patients with human epidermal growth factor receptor 2 (HER2) positive, negative or unknown disease are eligible for this trial; patients whose tumors are HER2 positive by either immunohistochemistry 3+ staining or demonstrate gene amplification by fluorescence in situ hybridization (FISH) may receive trastuzumab
• There must be negative tumor margins for invasive cancer and ductal carcinoma in situ (DCIS) in the case of mastectomy or lumpectomy; lobular carcinoma in situ (LCIS) is acceptable at the margin
• Patients with multi-centric breast cancer are eligible as long as all known disease is resected with negative margins, and have 0-3 positive axillary lymph nodes

• Patients must be registered within 84 days of the last breast surgery; patients must have undergone either modified radical mastectomy or lumpectomy; for patients undergoing sentinel node sampling or axillary dissection a simple mastectomy is acceptable; lumpectomy patients must receive radiation therapy; for patients treated with radiation therapy prior to chemotherapy, the patients should be registered on this study after the conclusion of radiation, with chemotherapy administration beginning within 7 days of registration

  * All primary breast and axillary node surgery must be completed prior to enrollment on study

• No previous trastuzumab, chemotherapy or hormonal therapy for this malignancy, except for tamoxifen therapy
• No previous anthracycline chemotherapy for any disease
• Patients with locally advanced breast cancer, inflammatory breast cancer or metastatic breast cancer are not eligible; patients with involvement of dermal lymphatics on pathology are not eligible, even if there are no clinical signs of inflammatory cancer
• Patients with bilateral, synchronous invasive breast cancer are eligible as long as both primary tumors; if a patient has an invasive cancer on one side that meets the eligibility criteria, and DCIS or LCIS on the contralateral side, the patient is eligible; DCIS or LCIS should be managed according to institutional guidelines
• Patients must be disease free from prior malignancies for > 5 years, except for curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix; patients with a history of invasive breast cancer, or DCIS are eligible if they have been disease free for > 5 years; patients with a history of LCIS are eligible regardless of the interval from diagnosis
• Common Toxicity Criteria (CTC) performance status 0-1
• Women must not be pregnant or nursing
• Concomitant exogenous hormone therapy, including oral contraceptives, post-menopausal hormone replacement therapy, and raloxifene must be stopped before patients can be enrolled

• Patients may have received up to 4 weeks of tamoxifen therapy for this malignancy and still be eligible for this study; patients who received tamoxifen or another selective estrogen receptor modulator (SERM) for prevention or for other indicators (e.g. osteoporosis) are eligible; tamoxifen therapy or other SERMs must be discontinued before the patient is enrolled on this study

  * The use of bisphosphonates for the treatment of osteoporosis is permitted; the use of raloxifene is not permitted are enrollment on this study

• Patients must have adequate organ function including no active congestive heart failure, and no myocardial infarction < 6 months from time of registration
• Absolute neutrophil count (ANC) >= 1,000/mm^3
• Platelet count >= 100,00/mm^3
• Creatinine =< 2.0 mg/dl
• Bilirubin =< 1.5 x upper limits of institutional normal
• Patients may be enrolled on adjuvant bisphosphonate studies; patients may be enrolled concurrently or sequentially on 40101 and bisphosphonate trials
• Patients may be enrolled on adjuvant hormonal studies approved by CALGB or Cancer Trials Support Unit (CTSU), such as the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT) trials

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (CA for 4 courses); Patients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.	Drug: doxorubicin hydrochloride; Given IV; Drug: AC regimen; Given IV
Experimental: Arm II (CA for 6 courses [closed to accrual 12/15/2007]); Patients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: cyclophosphamide; Given IV; Drug: doxorubicin hydrochloride; Given IV; Drug: AC regimen; Given IV
Experimental: Arm III (paclitaxel for 4 courses); Patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.	Drug: paclitaxel; Given IV; Drug: AC regimen; Given IV
Experimental: Arm IV (paclitaxel for 6 courses [closed 12/15/2007]); Patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: paclitaxel; Given IV; Drug: AC regimen; Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse Free Survival (RFS) 4 vs. 6 Cycles	To determine if longer therapy, 12 weeks, is superior to shorter therapy, 8 weeks, of either CA or paclitaxel for relapse-free survival for women with primary breast cancer with 0-3 positive axillary lymph nodes. An assessment of the superiority of 6 cycles over 4 cycles will be conducted. This analysis combines Arm I and Arm III together, and Arm II and Arm IV together.	from baseline up to 4 years
Duration of Disease Free Survival (RFS)	To determine the equivalence of paclitaxel to CA as adjuvant therapy for women with 0-3 positive axillary lymph nodes, for disease-free survival. Objective progression is defined as the appearance of local (chest wall, axillary, supraclavicular nodes) or distant metastases. The trial is designed to show the equivalence of the experimental agent T with the standard agent combination CA, thus the 4 and 6 course arms of each drug will be combined to conduct this analysis.	from baseline up to 6.4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	To determine the equivalence of paclitaxel to CA as adjuvant therapy for women with 0-3 positive axillary lymph nodes, for overall survival. OS will be measured from study entry until death due to any cause. Survivors will be censored at the date of last follow-up.. The trial is designed to show the equivalence of the experimental agent T with the standard agent combination CA, thus the 4 and 6 course arms of each drug will be combined to conduct this analysis.	from baseline up to 5 years
Adverse Events	To compare toxicities of short course CA and paclitaxel with long course CA and paclitaxel as adjuvant therapy for women with 0-3 positive axillary lymph node breast cancer. The percentage of patients that received a grade 3 or higher hematologic event will be reported here. We will be combining arm I with arm III, as well as arm II with arm IV. For a complete list of adverse events, please refer to the adverse events section.	from baseline up to 6 weeks post-treatment
Time to Distant Metastases	Local control and distant metastasis will be calculated as the cumulative incidence of first local relapse and first distant metastasis, respectively.	from baseline up to 15 years
Local Control	Local control will be calculated as the cumulative incidence of first local relapse.	from baseline up to 15 years
Overall Survival (OS) for 4 vs. 6 Cycles	To determine if longer therapy, 12 weeks, is superior to shorter therapy, 8 weeks, of either CA or paclitaxel for overall survival for women with primary breast cancer with 0-3 positive axillary lymph nodes. An assessment of the superiority of 6 cycles over 4 cycles will be conducted. This analysis combines Arm I and Arm III together, and Arm II and Arm IV together.	from baseline up to 4 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Lawrence N. Shulman, MD, Dana-Farber Cancer Institute

Publications and helpful links

General Publications

• Baldwin RM, Owzar K, Zembutsu H, Chhibber A, Kubo M, Jiang C, Watson D, Eclov RJ, Mefford J, McLeod HL, Friedman PN, Hudis CA, Winer EP, Jorgenson EM, Witte JS, Shulman LN, Nakamura Y, Ratain MJ, Kroetz DL. A genome-wide association study identifies novel loci for paclitaxel-induced sensory peripheral neuropathy in CALGB 40101. Clin Cancer Res. 2012 Sep 15;18(18):5099-109. doi: 10.1158/1078-0432.CCR-12-1590. Epub 2012 Jul 27.
• Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, O'Regan R, Martino S, Atkins JN, Mayer E, Schneider CJ, Kimmick G, Norton L, Muss H, Winer EP, Hudis C. Six cycles of doxorubicin and cyclophosphamide or Paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes: Cancer and Leukemia Group B 40101. J Clin Oncol. 2012 Nov 20;30(33):4071-6. doi: 10.1200/JCO.2011.40.6405. Epub 2012 Jul 23.
• Barginear M, Dueck AC, Allred JB, Bunnell C, Cohen HJ, Freedman RA, Hurria A, Kimmick G, Le-Rademacher JG, Lichtman S, Muss HB, Shulman LN, Copur MS, Biggs D, Ramaswamy B, Lafky JM, Jatoi A. Age and the Risk of Paclitaxel-Induced Neuropathy in Women with Early-Stage Breast Cancer (Alliance A151411): Results from 1,881 Patients from Cancer and Leukemia Group B (CALGB) 40101. Oncologist. 2019 May;24(5):617-623. doi: 10.1634/theoncologist.2018-0298. Epub 2018 Nov 8.
• Shulman LN, Berry DA, Cirrincione CT, Becker HP, Perez EA, O'Regan R, Martino S, Shapiro CL, Schneider CJ, Kimmick G, Burstein HJ, Norton L, Muss H, Hudis CA, Winer EP. Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance). J Clin Oncol. 2014 Aug 1;32(22):2311-7. doi: 10.1200/JCO.2013.53.7142. Epub 2014 Jun 16.

Study record dates

Study Major Dates

• Study Start: May 1, 2002
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: July 8, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): May 18, 2017
• Last Update Submitted That Met QC Criteria: April 12, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: stage II breast cancer; stage IB breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Paclitaxel; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: CALGB-40101; U10CA180821 (U.S. NIH Grant/Contract); CDR0000069444 (Registry Identifier: PDQ (Physician Data Query)); NCI-2009-00474 (Registry Identifier: CTRP (Clinical Trials Reporting System))