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Combination Chemotherapy With or Without Colony-Stimulating Factors in Treating Women With Breast Cancer
This study is ongoing, but not recruiting participants.
First Received: April 10, 2001   Last Updated: February 6, 2009   History of Changes
Sponsor: NCIC Clinical Trials Group
Collaborators: North Central Cancer Treatment Group
Southwest Oncology Group
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00014222
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as epoetin alfa and filgrastim may decrease the side effects of chemotherapy. It is not yet known which treatment regimen is most effective for breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy given with or without epoetin alfa in treating women who have undergone surgery for stage I, stage II, or stage III breast cancer.


Condition Intervention Phase
Breast Cancer
Biological: epoetin alfa
Biological: filgrastim
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: epirubicin hydrochloride
Drug: fluorouracil
Drug: paclitaxel
Procedure: adjuvant therapy
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Active Control
Official Title: A Phase III Adjuvant Trial Of Sequenced EC + Filgrastim + Epoetin Alfa Followed By Paclitaxel Versus Sequenced AC Followed By Paclitaxel Versus CEF As Therapy For Premenopausal Women And Early Postmenopausal Women Who Have Had Potentially Curative Surgery For Node Positive Or High Risk Node Negative Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: December 2000
Detailed Description:

OBJECTIVES:

Primary

  • Compare the disease-free survival of premenopausal or early postmenopausal women with previously resected node positive or high-risk node negative stage I-IIIB breast cancer treated with cyclophosphamide, epirubicin, and fluorouracil vs cyclophosphamide, epirubicin, filgrastim (G-CSF), and epoetin alfa followed by paclitaxel vs cyclophosphamide and doxorubicin followed by paclitaxel.

Secondary

  • Compare the overall survival of patients treated with these regimens.
  • Compare the rate of toxic effects of these regimens in this patient population.
  • Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to number of positive nodes (0 vs 1-3 vs 4-10 vs more than 10), type of prior surgery (total vs partial mastectomy), and estrogen receptor status (positive vs negative). Patients are randomized to one of three treatment arms.

  • Arm I: Patients receive epirubicin IV and fluorouracil IV on days 1-8 and oral cyclophosphamide on days 1-14. Treatment repeats every 28 days for 6 courses.
  • Arm II: Patients receive epirubicin IV and cyclophosphamide IV on day 1 and filgrastim (G-CSF) subcutaneously (SC) on days 2-13. Patients with a hemoglobin < 13.0 g/dL also receive epoetin alfa SC once weekly beginning within 1 week after the start of therapy and continuing as needed. Treatment repeats every 14 days for 6 courses.

Beginning 21 days after completion of epirubicin and cyclophosphamide, patients receive paclitaxel IV over 3 hours on day 1 and G-CSF and epoetin alfa as above. Treatment repeats every 21 days for 4 courses.

  • Arm III: Patients receive doxorubicin IV over 15 minutes and cyclophosphamide IV over 15 minutes on day 1. Treatment repeats every 21 days for 4 courses.

Beginning 21 days after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel as in arm II.

Treatment in all arms continues in the absence of disease progression or unacceptable toxicity.

All receptor positive patients receive oral tamoxifen or anastrozole (if tamoxifen is contraindicated) for 5 years after completion of chemotherapy.

Quality of life is assessed at baseline, weeks 4, 8, 12, and 20 (arm I), weeks 4, 8, 13, and 22 (arm II), weeks 3, 9, 12, and 21 (arm III), 9 months, 12 months, and then annually thereafter.

Patients are followed at 9 months, 12 months, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 2,100 patients (700 per treatment arm) will be accrued for this study within 4 years.

  Eligibility

Ages Eligible for Study:   up to 60 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the breast that is potentially curable

    • T0-4 (dermal involvement on pathology assessment only), N0-2, M0
    • No clinical T4 disease
  • Previously treated with one of the following:

    • Total mastectomy and level II axillary node dissection
    • Partial mastectomy and level II axillary node dissection with planned breast radiotherapy after completion of study*
    • Patients with a positive sentinel node biopsy must undergo level II axillary node dissection or sufficient nodal sampling NOTE: *If microscopic residual in situ or invasive disease is present at total or partial mastectomy margins, planned radiotherapy must also include a boost to the tumor bed
  • No residual tumor in the axilla after dissection
  • Axillary node positive

    • Negative nodes allowed if the tumor is ≥ 1 cm and 1 of the following criteria defining high-risk node-negative disease are met:

      • Histological grade III
      • Estrogen receptor negative
      • Lymphatic/vascular invasion
  • Hormone receptor status:

    • Estrogen receptor status known

PATIENT CHARACTERISTICS:

Age:

  • 60 and under

Sex:

  • Female

Menopausal status:

  • Pre- or postmenopausal

Performance status:

  • ECOG 0-2

Life expectancy:

  • At least 5 years

Hematopoietic:

  • WBC ≥ 3,000/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic:

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)

Renal:

  • Creatinine ≤ 1.5 times ULN

Cardiovascular:

  • LVEF ≥ limit of normal by MUGA or echocardiogram
  • No arrhythmia requiring ongoing treatment
  • No congestive heart failure
  • No documented coronary artery disease

Other:

  • No other malignancy except:

    • Adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
    • Ductal or lobular carcinoma in situ that has been curatively treated by surgery alone
    • Other prior malignancies (except breast cancer) curatively treated more than 5 years prior to study entry
  • No serious underlying medical illness or psychiatric or addictive disorder that would preclude study compliance
  • No known hypersensitivity to E. coli-derived products, mammalian-cell derived products, or any study agents
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective non-hormonal contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior immunotherapy for breast cancer
  • No concurrent pegfilgrastim or darbepoetin alfa (Arm II)

    • Allowed on arms 1 and 3 if medically necessary

Chemotherapy:

  • No prior chemotherapy for breast cancer

Endocrine therapy:

  • No prior hormonal therapy for breast cancer
  • No concurrent hormone replacement therapy
  • No concurrent selective estrogen-receptor modulators (e.g., raloxifene for the treatment or prevention of osteoporosis)
  • No concurrent oral contraceptives (i.e., birth control pills)
  • No other concurrent aromatase inhibitors

Radiotherapy:

  • See Disease Characteristics
  • No prior radiotherapy for breast cancer

Surgery:

  • See Disease Characteristics
  • No more than 12 weeks since prior total or partial mastectomy (including re-excision of margins)

Other:

  • At least 30 days since prior investigational drugs
  • No other concurrent investigational drugs
  • Concurrent bisphosphonates for the treatment or prevention of osteoporosis allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00014222

  Hide Study Locations
Locations
United States, Arizona
CCOP - Mayo Clinic Scottsdale Oncology Program
Scottsdale, Arizona, United States, 85259-5404
United States, Arkansas
Arkansas Cancer Institute
Pine Bluff, Arkansas, United States, 71603
Genesis Cancer Center
Hot Springs, Arkansas, United States, 71913
Little Rock Hematology-Oncology Associates
Little Rock, Arkansas, United States, 72205
Sparks Regional Medical Center
Fort Smith, Arkansas, United States, 72901-5128
United States, California
Scripps Cancer Center at Scripps Clinic
La Jolla, California, United States, 92037
Shasta Regional Medical Center
Redding, California, United States, 96001-0853
United States, Colorado
University of Colorado Cancer Center at University of Colorado Health Sciences Center
Aurora, Colorado, United States, 80010
United States, Connecticut
Greenwich Hospital Association
Greenwich, Connecticut, United States, 06830
United States, District of Columbia
Sibley Memorial Hospital
Washington, District of Columbia, United States, 20016
United States, Florida
Lynn Regional Cancer Center of Boca Raton Community Hospital
Boca Raton, Florida, United States, 33466
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0232
Orange Park Cancer Center
Orange Park, Florida, United States, 32073
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States, 32224
United States, Georgia
CCOP - Atlanta Regional
Atlanta, Georgia, United States, 30342-1701
United States, Hawaii
MBCCOP - Hawaii
Honolulu, Hawaii, United States, 96813
United States, Illinois
Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, United States, 60153-5589
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
La Grange Oncology Associates
La Grange, Illinois, United States, 60525
Swedish-American Regional Cancer Center
Rockford, Illinois, United States, 61104-2315
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
United States, Indiana
Evansville Cancer Center
Evansville, Indiana, United States, 47715
Northern Indiana Oncology Associates - South Bend
South Bend, Indiana, United States, 46617
United States, Iowa
CCOP - Cedar Rapids Oncology Project
Cedar Rapids, Iowa, United States, 52403-1206
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, United States, 50309-1016
Siouxland Hematology-Oncology Associates
Sioux City, Iowa, United States, 51101-1733
United States, Kansas
CCOP - Wichita
Wichita, Kansas, United States, 67214-3882
United States, Kentucky
Central Baptist Hospital
Lexington, Kentucky, United States, 40503
Consultants in Blood Disorders and Cancer
Louisville, Kentucky, United States, 40207
Graves-Gilbert Clinic
Bowling Green, Kentucky, United States, 42102-9007
United States, Louisiana
Cancer Treatment Center at Christus Schumpert St. Mary Place
Shreveport, Louisiana, United States, 71101
CCOP - Ochsner
New Orleans, Louisiana, United States, 70121
Willis - Knighton South Center for Women's Health
Shreveport, Louisiana, United States, 71118
United States, Maine
Maine Center for Cancer Medicine and Blood Disorders - Scarborough
Scarborough, Maine, United States, 04074
Maine General Medical Center - Waterville
Waterville, Maine, United States, 04901
United States, Maryland
Associates in Oncology and Hematology
Rockville, Maryland, United States, 20850
St. Joseph Medical Center
Towson, Maryland, United States, 21204
Suburban Hospital Cancer Program
Bethesda, Maryland, United States, 20817
United States, Massachusetts
Baystate Regional Cancer Program at D'Amour Center for Cancer Care
Springfield, Massachusetts, United States, 01107
United States, Minnesota
Cancer Care Center at St. Luke's Hospital
Duluth, Minnesota, United States, 55805
CCOP - Duluth
Duluth, Minnesota, United States, 55805
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Columbia Comprehensive Cancer Care Clinic
Columbia, Missouri, United States, 65201
Saint Louis University Cancer Center
Saint Louis, Missouri, United States, 63110
United States, Nebraska
Cancer Center at Creighton University Medical Center
Omaha, Nebraska, United States, 68131-2197
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, United States, 68106
Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha
Omaha, Nebraska, United States, 68114-4199
United States, New Jersey
Somerset Medical Center
Somerville, New Jersey, United States, 08876
Valley Hospital - Ridgewood
Ridgewood, New Jersey, United States, 07450-2736
United States, New York
Advanced Oncology Associates
Armonk, New York, United States, 10504
Hematology-Oncology Associates of Rockland, P.C.
New City, New York, United States, 10956
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
Nalitt Cancer Institute at Staten Island University Hospital
Staten Island, New York, United States, 10305
Queens Medical Associates, PC
Fresh Meadows, New York, United States, 11365
Winthrop University Hospital
Mineola, New York, United States, 11501
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
Leo W. Jenkins Cancer Center at Pitt County Memorial Hospital
Greenville, North Carolina, United States, 27858-4354
United States, North Dakota
CCOP - Merit Care Hospital
Fargo, North Dakota, United States, 58122
Medcenter One Health System
Bismarck, North Dakota, United States, 58501-5505
United States, Ohio
CCOP - Dayton
Dayton, Ohio, United States, 45429
CCOP - Toledo Community Hospital
Toledo, Ohio, United States, 43623-3456
Gabrail Cancer Center - Canton Office
Canton, Ohio, United States, 44718
Lawrence M. Stallings Medical Practice
Wooster, Ohio, United States, 44691
Oncology Hematology Care, Incorporated - Mt. Auburn/Taft Road
Cincinnati, Ohio, United States, 45242
United States, Pennsylvania
Cancer Center of Drexel University College of Medicine
Philadelphia, Pennsylvania, United States, 19129
CCOP - Geisinger Clinic and Medical Center
Danville, Pennsylvania, United States, 17822-2001
Central Montgomery Medical Center
Lansdale, Pennsylvania, United States, 19446-1200
Pottstown Memorial Regional Cancer Center
Pottstown, Pennsylvania, United States, 19464
United States, South Carolina
CCOP - Upstate Carolina
Spartanburg, South Carolina, United States, 29303
Santee Hematology Oncology
Sumter, South Carolina, United States, 29150
United States, South Dakota
CCOP - Sioux Community Cancer Consortium
Sioux Falls, South Dakota, United States, 57104
Rapid City Regional Hospital
Rapid City, South Dakota, United States, 57709
United States, Tennessee
Associates in Oncology and Hematology
Chattanooga, Tennessee, United States, 37404
United States, Texas
Lone Star Oncology - Austin
Austin, Texas, United States, 78759
Medical City Dallas Hospital
Dallas, Texas, United States, 75230
United States, Utah
Cancer Associates of Northern Utah
Ogden, Utah, United States, 84403
United States, Virginia
Arlington-Fairfax Hematology/Oncology, PC
Arlington, Virginia, United States, 22205
Northern Virginia Oncology Group, P.C.
Fairfax, Virginia, United States, 22031
United States, Wyoming
Ivinson Memorial Hospital
Laramie, Wyoming, United States, 82070
Canada, British Columbia
British Columbia Cancer Agency - Centre for the Southern Interior
Kelowna, British Columbia, Canada, V1Y 5L3
British Columbia Cancer Agency - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Fraser Valley Cancer Centre at Surrey Memorial Hospital
Surrey, British Columbia, Canada, V3V 1Z2
Nanaimo Cancer Clinic at Nanaimo Regional General Hospital
Nanaimo, British Columbia, Canada, V9S 2B7
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, New Brunswick
Moncton Hospital
Moncton, New Brunswick, Canada, E1C 6ZB
Saint John Regional Hospital
Saint John, New Brunswick, Canada, E2L 4L2
Canada, Newfoundland and Labrador
Newfoundland Cancer Treatment and Research Foundation
St. Johns, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Nova Scotia
Nova Scotia Cancer Centre at Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
Algoma Regional Cancer Program at Sault Area Hospital
Sault Sainte Marie, Ontario, Canada, P6A 2C4
Cancer Care Ontario - Windsor Regional Cancer Centre
Windsor, Ontario, Canada, N8W 2X3
Cancer Centre of Southeastern Ontario
Kingston, Ontario, Canada, K7L 5P9
Durham Regional Cancer Centre at Lakeridge Health Oshawa
Oshawa, Ontario, Canada, L1G 2B9
Grand River Regional Cancer Centre at Grand River Hospital
Kitchner, Ontario, Canada, N2G 1G3
Hotel Dieu Health Sciences Hospital - Niagara
St. Catharines, Ontario, Canada, L2R 5K3
Regional Cancer Care at Thunder Bay Regional Health Sciences Centre
Thunder Bay, Ontario, Canada, P7B 6V4
Margaret and Charles Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V 5C2
Mount Sinai Hospital - Toronto
Toronto, Ontario, Canada, M5G 1X5
Northeastern Ontario Regional Cancer Centre
Sudbury, Ontario, Canada, P3E 5J1
Ottawa Regional Cancer Centre at Ottawa Hospital - General Campus
Ottawa, Ontario, Canada, K1H 1C4
Peterborough Oncology Clinic
Peterborough, Ontario, Canada, K9H 7B6
London Regional Cancer Program at London Health Sciences Centre
London, Ontario, Canada, N6A 4L6
Royal Victoria Hospital of Barrie
Barrie, Ontario, Canada, L4M 6M2
Scarborough Hospital - General Site
Scarborough, Ontario, Canada, M1P 2V5
St. Joseph's Health Centre - Toronto
Toronto, Ontario, Canada, M6R 1B5
St. Michael's Hospital - Toronto
Toronto, Ontario, Canada, M5B 1W8
Trillium Health Centre - Mississauga
Mississauga, Ontario, Canada, L5B 1B8
Toronto Sunnybrook Regional Cancer Centre
Toronto, Ontario, Canada, M4N 3M5
Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Canada, Prince Edward Island
Prince Edward Island Cancer Centre at Queen Elizabeth Hospital
Charlottetown, Prince Edward Island, Canada, C1A 8T5
Canada, Quebec
Centre Hospitalier de l'Universite de Montreal
Montreal, Quebec, Canada, H2L 4M1
Hopital Charles Lemoyne
Greenfield Park, Quebec, Canada, J4V 2H1
Hotel Dieu de Montreal
Montreal, Quebec, Canada, H2W 1T8
Maisonneuve-Rosemont Hospital
Montreal, Quebec, Canada, H1T 2M4
Canada, Saskatchewan
Allan Blair Cancer Centre at Pasqua Hospital
Regina, Saskatchewan, Canada, S4T 7T1
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, Canada, S7N 4H4
Sponsors and Collaborators
NCIC Clinical Trials Group
North Central Cancer Treatment Group
Southwest Oncology Group
Investigators
Study Chair: Mark N. Levine, MD Margaret and Charles Juravinski Cancer Centre
Study Chair: Edith A. Perez, MD Mayo Clinic
Investigator: Kathy S. Albain, MD Loyola University
  More Information

Additional Information:
Publications:
Burnell MJ, O'Connor EM, Chapman JW, et al.: Triple-negative receptor status and prognosis in the NCIC CTG MA.21 adjuvant breast cancer trial. [Abstract] J Clin Oncol 26 (Suppl 15): A-550, 2008.
Burnell MJ, Levine MN, Chapman JA, et al.: A phase III adjuvant trial of sequenced EC + filgrastim + epoetin-alpha followed by paclitaxel compared to sequenced AC followed by paclitaxel compared to CEF in women with node-positive or high-risk node-negative breast cancer (NCIC CTG MA.21). [Abstract] J Clin Oncol 25 (Suppl 18): A-550, 2007.
Burnell M, Levine M, Chapman JA, et al.: A randomized trial of CEF versus dose dense EC followed by paclitaxel versus AC followed by paclitaxel in women with node positive or high risk node negative breast cancer, NCIC CTG MA.21: results of an interim analysis. [Abstract] 29th Annual San Antonio Breast Cancer Symposium, December 14-17, 2006, San Antonio, Texas. A-53, 2006.

Study ID Numbers: CDR0000068520, CAN-NCIC-MA21, AMGEN-CAN-NCIC-MA21, NCCTG-CAN-NCIC-MA21, BMS-CAN-NCIC-MA21, JANSSEN-ORTHO-CAN-NCIC-MA21, PFIZER-CAN-NCIC-MA21, SWOG-CAN-NCIC-MA21
Study First Received: April 10, 2001
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00014222     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer

Additional relevant MeSH terms:
Antimetabolites
Epoetin Alfa
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Hematologic Agents
Physiological Effects of Drugs
Cyclophosphamide
Antibiotics, Antineoplastic
Neoplasms by Site
Therapeutic Uses
Alkylating Agents
Breast Diseases
Skin Diseases
Hematinics
Mitosis Modulators
Adjuvants, Immunologic
Breast Neoplasms
Antimitotic Agents
Epirubicin
Immunosuppressive Agents
Doxorubicin
Pharmacologic Actions
Neoplasms
Paclitaxel
Fluorouracil
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on November 27, 2009