Combination Chemotherapy With or Without Colony-stimulating Factors in Treating Women With Breast Cancer

NCT00014222 | Completed Phase 3 Results DMC FDA Drug

• 10 other identifiers: MA21CAN-NCIC-MA21AMGEN-CAN-NCIC-MA21NCCTG-CAN-NCIC-MA21BMS-CAN-NCIC-MA21JANSSEN-ORTHO-CAN-NCIC-MA21PFIZER-CAN-NCIC-MA21SWOG-CAN-NCIC-MA21CDR0000068520CALGB-CAN-NCIC-MA21
• Study Type: interventional
• Target: 2,104
• Locations: 2 countries
• Sites: 78

Brief Summary

RATIONALE:

1. 1.. To compare the effects on breast cancer of three different combinations of drugs which are commonly used to treat this disease.
2. 2.. It is not yet known which treatment regimen is most effective for breast cancer.

Conditions

Breast Cancer

Keywords

stage I breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer

Outcome Measures

Primary Outcomes (1)

• Disease Free Survival

  Disease free survival was defined as the time from randomization to the time of recurrence of the primary disease. Local or nodal recurrence and metastatic disease were considered a recurrence of the primary tumour. Patients who had contralateral breast cancer or a second primary malignancy, or died from some cause other than disease were censored as relapse-free at the time of death. Patients who had not relapsed were censored at longest follow-up or at non-breast cancer death. As required, adjudication was used to assess reports of recurrence.

  13 years

Secondary Outcomes (1)

• Overall Survival

  13 years

Study Arms (3)

Arm 1: CEF

ACTIVE COMPARATOR

6 cycles - q 28 days (6 months) - Cyclophosphamide 75 mg/m2 - po - Days 1-14 - Epirubicin 60 mg/m2 - IV - Days 1 and 8 - 5 Fluorouracil: 500mg/m2 - IV - Days 1 and 8 + Continuous Antibiotic Prophylaxis with Cotrimoxazole 960 mg (i.e.2x480 mg tablets) po-bid or Ciprofloxacin 500 mg - po-bid

Drug: cyclophosphamide; Drug: epirubicin hydrochloride; Drug: fluorouracil

Arm 2: EC/T

ACTIVE COMPARATOR

6 cycles - q 14 days (3 months) - Epirubicin 120 mg/m2 - IV - Day 1 - Cyclophosphamide 830 mg/m2 - IV - Day 1 - Filgrastim 5μg/kg/d - SC - Days 2 - 13 + Epoetin Alfa 40,000 IU - SC - once weekly (to begin within 1 week after start of protocol therapy as needed) 21 days from last administration of EC (EC/T) 4 cycles - q 21 days (3 months) - Adriamycin 60 mg/m2 - IV - Day 1 - Cyclophosphamide 600 mg/m2 - IV - Day 1 - 21 days from last administration of AC 4 cycles - q 21 days (3 months) - Paclitaxel 175 mg/m2 IV 3 hour infusion

Biological: epoetin alfa; Biological: filgrastim; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: paclitaxel

Arm 3: AC/T

ACTIVE COMPARATOR

4 cycles - q 21 days (3 months) - Adriamycin 60 mg/m2 - IV - Day 1 - Cyclophosphamide 600 mg/m2 - IV - Day 1 21 days from last administration of AC 4 cycles - q 21 days (3 months) - Paclitaxel 175 mg/m2 IV 3 hour infusion

Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: paclitaxel

Interventions

epoetin alfa BIOLOGICAL

40,000 IU

Arm 2: EC/T

filgrastim BIOLOGICAL

5 mg/kg/d - days 2-13

Arm 2: EC/T

cyclophosphamide DRUG

75, 600 and 830 mg/m2

Arm 1: CEF; Arm 2: EC/T; Arm 3: AC/T

doxorubicin hydrochloride DRUG

60 mg/m2

Arm 2: EC/T; Arm 3: AC/T

epirubicin hydrochloride DRUG

60 mg/m2

Arm 1: CEF

fluorouracil DRUG

500mg/m2

Arm 1: CEF

paclitaxel DRUG

175 mg/m2

Arm 2: EC/T; Arm 3: AC/T

Eligibility Criteria

• Age: Up to 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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 adjuvant chemotherapy regimen\* * Patients with a positive sentinel node biopsy must undergo level II axillary node dissection or sufficient nodal sampling * 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 or more of the following criteria defining high-risk node-negative disease are met: * Histological grade III or, * Estrogen receptor negative or, * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead
• North Central Cancer Treatment Group: collaborator
• SWOG Cancer Research Network: collaborator
• Cancer and Leukemia Group B: collaborator

Study Sites (78)

Sparks-Arkansas Oklahoma Cancer Treatment Centre

Fort Smith, Arkansas, 72901, United States

Location

Hematology Oncology Services of Arkansas

Little Rock, Arkansas, 72205, United States

Location

Scripps Cancer Center

La Jolla, California, 92037, United States

Location

University of Colorado Cancer Centre

Aurora, Colorado, 80010-0510, United States

Location

Greenwich Hospital - Bendheim Cancer Center

Greenwich, Connecticut, 06830, United States

Location

Sibley Memorial Hospital, Oncology Research

Washington D.C., District of Columbia, 20016, United States

Location

Comprehensive Cancer Care Centre at Boca Raton

Boca Raton, Florida, 33428, United States

Location

University of Florida

Gainesville, Florida, 32610-0277, United States

Location

Florida Oncology Associates

Orange Park, Florida, 32073, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637-1470, United States

Location

Therapy Associates, Inc., Hematology/Oncology

Evansville, Indiana, 47715, United States

Location

Lexington Oncology Assts./Central Baptist Hospital

Lexington, Kentucky, 40503, United States

Location

Consultants in Blood Disorders and Cancer

Louisville, Kentucky, 40207, United States

Location

CHRISTUS Schumpert Medical Center - Hem/Onc Clinic

Shreveport, Louisiana, 71101, United States

Location

Willis-Knighton Cancer Center

Shreveport, Louisiana, 71103-3, United States

Location

Maine Center for Cancer Medicine and Blood Disorders

Scarborough, Maine, 04074-9308, United States

Location

Maine General Medical Center

Waterville, Maine, 04901, United States

Location

Suburban Hospital Cancer Program

Bethesda, Maryland, 20817, United States

Location

Associates in Oncology/Hematology

Rockville, Maryland, 20850, United States

Location

Saint Joseph Medical Center, Cancer Care Program

Towson, Maryland, 21204, United States

Location

Baystate Regional Cancer Program

Springfield, Massachusetts, 01107, United States

Location

St. Luke's Cancer Care Centre

Duluth, Minnesota, 55802, United States

Location

University of Minnesota Cancer Centre

Minneapolis, Minnesota, 55455, United States

Location

Columbia-Capitol Comprehensive Care Clinics

Jefferson City, Missouri, 65109, United States

Location

Saint Louis University Hospital

St Louis, Missouri, 63110-0250, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Creighton University Cancer Centre

Omaha, Nebraska, 68131, United States

Location

Advanced Oncology Associates

Armonk, New York, 10504, United States

Location

Queens Medical Associates, PC

Fresh Meadows, New York, 11366, United States

Location

Winthrop University Hospital Onc/Hem

Mineola, New York, 11501, United States

Location

Hematology Oncol. Associates Rockland

Nyack, New York, 10960, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Staten Island University Hospital

Staten Island, New York, 10305, United States

Location

Our Lady of Mercy Medical Center

The Bronx, New York, 10466, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

ECU School of Medicine, Leo Jenkins Cancer Center

Greenville, North Carolina, 27858, United States

Location

Oncology/Hematology Care, Inc.

Cincinnati, Ohio, 45242, United States

Location

Pottstown Memorial Regional Cancer Centre

Pottstown, Pennsylvania, 19464, United States

Location

Santee Hematology Oncology

Sumter, South Carolina, 29150, United States

Location

University Oncology and Hematology Associates

Chattanooga, Tennessee, 37404, United States

Location

Lone Star Oncology Consultants, PA

Austin, Texas, 78759, United States

Location

Center for Oncology Research and Treatment

Dallas, Texas, 75230, United States

Location

Northern Utah Associates

Ogden, Utah, 84403, United States

Location

Arlington-Fairfax Hematology Oncology P.C.

Arlington, Virginia, 22205, United States

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

The Moncton Hospital

Moncton, New Brunswick, E1C 6Z8, Canada

Location

Atlantic Health Sciences Corporation

Saint John, New Brunswick, E2L 4L2, Canada

Location

Dr. H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, AIB 3V6, Canada

Location

QEII Health Sciences Center

Halifax, Nova Scotia, B3H 1V7, Canada

Location

The Royal Victoria Hospital

Barrie, Ontario, L4M 6M2, Canada

Location

Northeast Cancer Center Health Sciences

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, K7L 5P9, Canada

Location

Grand River Regional Cancer Centre

Kitchener, Ontario, N2G 1G3, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Lakeridge Health Oshawa

Oshawa, Ontario, L1G 2B9, Canada

Location

Ottawa Health Research Institute - General Division

Ottawa, Ontario, K1H 8L6, Canada

Location

Algoma District Cancer Program

Sault Ste. Marie, Ontario, P6B 0A8, Canada

Location

The Scarborough Hospital

Scarborough Village, Ontario, M1P 2V5, Canada

Location

Niagara Health System

St. Catharines, Ontario, L2R 7C6, Canada

Location

Thunder Bay Regional Health Science Centre

Thunder Bay, Ontario, P7B 6V4, Canada

Location

Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Trillium Health Centre - West Toronto

Toronto, Ontario, M9C 1A5, Canada

Location

Windsor Regional Cancer Centre

Windsor, Ontario, N8W 2X3, Canada

Location

PEI Cancer Treatment Centre,Queen Elizabeth Hospital

Charlottetown, Prince Edward Island, C1A 8T5, Canada

Location

Hopital Charles LeMoyne

Greenfield Park, Quebec, J4V 2H1, Canada

Location

Hopital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

CHUM - Hopital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

CHUM - Hotel Dieu du Montreal

Montreal, Quebec, H2W 1T8, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Related Publications (3)

• 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.

  RESULT

• 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.

  RESULT

• 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.

  RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Epoetin Alfa; Filgrastim; Cyclophosphamide; Doxorubicin; Epirubicin; Fluorouracil; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Granulocyte Colony-Stimulating Factor; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Results Point of Contact

• Title: Bingshu Chen
• Organization: Canadian Cancer Trials Group

bechen@ctg.queensu.ca

613-533-6000

Study Officials

• Mark N. Levine, MD

  Margaret and Charles Juravinski Cancer Centre

  STUDY CHAIR

• Edith A. Perez, MD

  Mayo Clinic

  STUDY CHAIR

• Kathy S. Albain, MD

  Loyola University

  STUDY CHAIR

• Margot Burnell

  Atlantic Health Sciences Corporation, Saint John NB

  STUDY CHAIR

• Hope Rugo

  Cancer and Leukemia Group B

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2001
• First Posted: January 27, 2003
• Study Start: December 4, 2000
• Primary Completion: February 10, 2014
• Study Completion: March 17, 2014
• Last Updated: October 5, 2020
• Results First Posted: March 10, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (34); US (44)