Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	60 and under	Other	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, NCT00014222

Trial Description

Summary

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.

Further Study Information

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 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

Trial Contact Information

Trial Lead Organizations/Sponsors

NCIC-Clinical Trials Group

Mark Norman Levine

Study Chair

Edith A. Perez

Study Chair

Kathy S. Albain

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00014222
Information obtained from ClinicalTrials.gov on March 18, 2010

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