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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
Sponsors and Collaborators: National Cancer Institute of Canada
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

Genetics Home Reference related topics: breast cancer
MedlinePlus related topics: Breast Cancer Cancer Surgery
Drug Information available for: Cyclophosphamide Fluorouracil Erythropoietin Doxorubicin Doxorubicin hydrochloride Paclitaxel Epirubicin hydrochloride Epirubicin Myocet Epoetin alfa Filgrastim
U.S. FDA Resources
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

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

  Show 116 Study Locations
Sponsors and Collaborators
National Cancer Institute of Canada
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

Study placed in the following topic categories:
Antimetabolites
Epoetin Alfa
Skin Diseases
Immunologic Factors
Hematinics
Adjuvants, Immunologic
Breast Neoplasms
Antimitotic Agents
Cyclophosphamide
Epirubicin
Immunosuppressive Agents
Doxorubicin
Anti-Bacterial Agents
Paclitaxel
Fluorouracil
Tubulin Modulators
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Alkylating Agents
Breast Diseases

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

ClinicalTrials.gov processed this record on May 06, 2009