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Breast CancerPhase 3NCT00014222

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

A Phase 3 study testing epoetin alfa, filgrastim and cyclophosphamide in people with Breast Cancer, run by NCIC Clinical Trials Group at 78 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages Up to 60 years, women only
Conditions the study is for
Breast Cancer
What is being tested?
epoetin alfa, filgrastim and cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2,104 participants
Where
78 sitesin 2 countries
Study dates
4 Dec 2000to 17 Mar 2014
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 60 years
  • Women only
  • No healthy volunteers
  • Child, Adult

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

Trial locations and contacts

78 sites in 2 countries.

78 sites in 2 countries

United States44 sites

  • Arlington-Fairfax Hematology Oncology P.C.

    Arlington, Virginia, 22205

  • Advanced Oncology Associates

    Armonk, New York, 10504

  • University of Colorado Cancer Centre

    Aurora, Colorado, 80010-0510

  • Lone Star Oncology Consultants, PA

    Austin, Texas, 78759

  • Suburban Hospital Cancer Program

    Bethesda, Maryland, 20817

  • Comprehensive Cancer Care Centre at Boca Raton

    Boca Raton, Florida, 33428

  • University Oncology and Hematology Associates

    Chattanooga, Tennessee, 37404

  • The University of Chicago Medical Center

    Chicago, Illinois, 60637-1470

  • Oncology/Hematology Care, Inc.

    Cincinnati, Ohio, 45242

  • Center for Oncology Research and Treatment

    Dallas, Texas, 75230

  • St. Luke's Cancer Care Centre

    Duluth, Minnesota, 55802

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Therapy Associates, Inc., Hematology/Oncology

    Evansville, Indiana, 47715

  • Sparks-Arkansas Oklahoma Cancer Treatment Centre

    Fort Smith, Arkansas, 72901

  • Queens Medical Associates, PC

    Fresh Meadows, New York, 11366

  • University of Florida

    Gainesville, Florida, 32610-0277

  • ECU School of Medicine, Leo Jenkins Cancer Center

    Greenville, North Carolina, 27858

  • Greenwich Hospital - Bendheim Cancer Center

    Greenwich, Connecticut, 06830

  • Columbia-Capitol Comprehensive Care Clinics

    Jefferson City, Missouri, 65109

  • Scripps Cancer Center

    La Jolla, California, 92037

  • Lexington Oncology Assts./Central Baptist Hospital

    Lexington, Kentucky, 40503

  • Hematology Oncology Services of Arkansas

    Little Rock, Arkansas, 72205

  • Consultants in Blood Disorders and Cancer

    Louisville, Kentucky, 40207

  • Winthrop University Hospital Onc/Hem

    Mineola, New York, 11501

  • University of Minnesota Cancer Centre

    Minneapolis, Minnesota, 55455

  • Hematology Oncol. Associates Rockland

    Nyack, New York, 10960

  • Northern Utah Associates

    Ogden, Utah, 84403

  • Nebraska Methodist Hospital

    Omaha, Nebraska, 68114

  • Creighton University Cancer Centre

    Omaha, Nebraska, 68131

  • Florida Oncology Associates

    Orange Park, Florida, 32073

  • Pottstown Memorial Regional Cancer Centre

    Pottstown, Pennsylvania, 19464

  • University of Rochester

    Rochester, New York, 14642

  • Associates in Oncology/Hematology

    Rockville, Maryland, 20850

  • Maine Center for Cancer Medicine and Blood Disorders

    Scarborough, Maine, 04074-9308

  • CHRISTUS Schumpert Medical Center - Hem/Onc Clinic

    Shreveport, Louisiana, 71101

  • Willis-Knighton Cancer Center

    Shreveport, Louisiana, 71103-3

  • Baystate Regional Cancer Program

    Springfield, Massachusetts, 01107

  • Saint Louis University Hospital

    St Louis, Missouri, 63110-0250

  • Staten Island University Hospital

    Staten Island, New York, 10305

  • Santee Hematology Oncology

    Sumter, South Carolina, 29150

  • Our Lady of Mercy Medical Center

    The Bronx, New York, 10466

  • Saint Joseph Medical Center, Cancer Care Program

    Towson, Maryland, 21204

  • Sibley Memorial Hospital, Oncology Research

    Washington D.C., District of Columbia, 20016

  • Maine General Medical Center

    Waterville, Maine, 04901

Other trials in United States

Canada34 sites

  • The Royal Victoria Hospital

    Barrie, Ontario, L4M 6M2

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • PEI Cancer Treatment Centre,Queen Elizabeth Hospital

    Charlottetown, Prince Edward Island, C1A 8T5

  • Northeast Cancer Center Health Sciences

    Greater Sudbury, Ontario, P3E 5J1

  • Hopital Charles LeMoyne

    Greenfield Park, Quebec, J4V 2H1

  • QEII Health Sciences Center

    Halifax, Nova Scotia, B3H 1V7

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • BCCA - Cancer Centre for the Southern Interior

    Kelowna, British Columbia, V1Y 5L3

  • Cancer Centre of Southeastern Ontario at Kingston

    Kingston, Ontario, K7L 5P9

  • Grand River Regional Cancer Centre

    Kitchener, Ontario, N2G 1G3

  • London Regional Cancer Program

    London, Ontario, N6A 4L6

  • The Moncton Hospital

    Moncton, New Brunswick, E1C 6Z8

  • Hopital Maisonneuve-Rosemont

    Montreal, Quebec, H1T 2M4

  • CHUM - Hopital Notre-Dame

    Montreal, Quebec, H2L 4M1

  • CHUM - Hotel Dieu du Montreal

    Montreal, Quebec, H2W 1T8

  • Lakeridge Health Oshawa

    Oshawa, Ontario, L1G 2B9

  • Ottawa Health Research Institute - General Division

    Ottawa, Ontario, K1H 8L6

  • Allan Blair Cancer Centre

    Regina, Saskatchewan, S4T 7T1

  • Atlantic Health Sciences Corporation

    Saint John, New Brunswick, E2L 4L2

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan, S7N 4H4

  • Algoma District Cancer Program

    Sault Ste. Marie, Ontario, P6B 0A8

  • The Scarborough Hospital

    Scarborough Village, Ontario, M1P 2V5

  • Niagara Health System

    St. Catharines, Ontario, L2R 7C6

  • Dr. H. Bliss Murphy Cancer Centre

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

  • BCCA - Fraser Valley Cancer Centre

    Surrey, British Columbia, V3V 1Z2

  • Thunder Bay Regional Health Science Centre

    Thunder Bay, Ontario, P7B 6V4

  • Odette Cancer Centre

    Toronto, Ontario, M4N 3M5

  • St. Michael's Hospital

    Toronto, Ontario, M5B 1W8

  • Mount Sinai Hospital

    Toronto, Ontario, M5G 1X5

  • Univ. Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

  • Trillium Health Centre - West Toronto

    Toronto, Ontario, M9C 1A5

  • BCCA - Vancouver Cancer Centre

    Vancouver, British Columbia, V5Z 4E6

  • Windsor Regional Cancer Centre

    Windsor, Ontario, N8W 2X3

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

About this study

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

RATIONALE:

  1. . To compare the effects on breast cancer of three different combinations of drugs which are commonly used to treat this disease.
  2. . 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.

Read the 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 and 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, day 1 of cycles 2, 3 4 and 6 (arm I), days 1 of cycles 3 and and day 1 of cycles 1 and 4 of paclitaxel (arm II), day 1 of cycles 2 and 3, day 1 of cycles 1 and 4 of paclitaxel, (arm III), 9 months, 12 months, and then annually thereafter until 5 years

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.

Conditions
Breast Cancer
Being tested
epoetin alfa, filgrastim, cyclophosphamide, doxorubicin hydrochloride, epirubicin hydrochloride
Keywords
stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00014222
Study groupRoleWhat they receive
Arm 1: CEFActive comparator6 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
Receives: Drug: cyclophosphamide; Drug: epirubicin hydrochloride; Drug: fluorouracil
Arm 2: EC/TActive comparator6 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
Receives: Biological: epoetin alfa; Biological: filgrastim; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: paclitaxel
Arm 3: AC/TActive comparator4 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
Receives: Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 13 years

Secondary outcomes (1)

  1. Overall Survival

    Overall survival was defined as the time from randomization to the time of death from any cause, with censoring at longest follow-up.

    Measured: 13 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study start4 Dec 2000
  3. Primary completion10 Feb 2014
  4. Study completion17 Mar 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
2,104 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00014222
Sponsor's protocol ID
MA21
Other IDs
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, CDR0000068520
Status last verified
Mar 2020
First submitted
10 Apr 2001
Last updated
5 Oct 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing epoetin alfa, filgrastim and cyclophosphamide in people with Breast Cancer, run by NCIC Clinical Trials Group at 78 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 78 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease Free Survival (time frame: 13 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00014222, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2020.

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