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A Three-Arm Randomized Trial to Compare Adjuvant Adriamycin and Cyclophosphamide Followed by Taxotere (AC-T); Adriamycin and Taxotere (AT); and Adriamycin, Taxotere, and Cyclophosphamide (ATC) in Breast Cancer Patients With Positive Axillary Lymph Nodes

Phase 3
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

A Three-Arm Randomized Trial to Compare Adjuvant Adriamycin and Cyclophosphamide Followed by Taxotere (AC-T); Adriamycin and Taxotere (AT); and Adriamycin, Taxotere, and Cyclophosphamide (ATC) in Breast Cancer Patients With Positive Axillary Lymph Nodes


- Compare the efficacy of adjuvant doxorubicin, cyclophosphamide, and docetaxel given
concurrently vs adjuvant doxorubicin and cyclophosphamide followed by docetaxel, in
terms of overall survival and disease-free survival, of women with breast cancer and
positive axillary lymph nodes.

- Compare the efficacy of adjuvant doxorubicin and docetaxel vs regimens containing
cyclophosphamide in these patients.

- Compare the toxic effects of these regimens in these patients.

- Compare the quality of life of patients treated with these regimens. (Quality of life
substudy closed to accrual as of 7/20/01.)

- Compare the differences in amenorrhea in premenopausal women in each treatment arm and
its relationship to symptoms, quality of life (quality of life substudy closed to
accrual as of 7/20/01), disease-free survival, and overall survival.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
participating center, number of positive nodes (1-3 vs 4-9 vs at least 10), sequential
tamoxifen or anastrozole administration (yes vs no), and type of prior surgery and
radiotherapy plan (mastectomy with no local or regional radiotherapy vs mastectomy with
local and/or regional radiotherapy vs lumpectomy with local radiotherapy vs lumpectomy with
local and regional radiotherapy). Patients are randomized to one of three treatment arms.

- Arm 1: Patients receive doxorubicin IV over 15 minutes and cyclophosphamide IV over 30
minutes every 21 days for 4 courses. Three weeks after the last dose of this
combination, patients receive docetaxel IV over 1 hour every 21 days for 4 courses.

- Arm 2: Patients receive doxorubicin IV over 15 minutes and docetaxel IV over 1 hour
every 21 days for 4 courses.

- Arm 3: Patients receive doxorubicin IV over 15 minutes, cyclophosphamide IV over 30
minutes, and docetaxel IV over 1 hour every 21 days for 4 courses.

Patients in all arms who are estrogen receptor-positive and/or progesterone
receptor-positive receive oral tamoxifen daily for 5 years beginning within 3-12 weeks of
completion of chemotherapy. Patients who are postmenopausal may receive alternative hormonal
therapy at the discretion of the treating physician.

Some patients may receive postmastectomy radiotherapy on SWOG-S9927 or NCIC-MA.20 after
recovery from chemotherapy.

Quality of life and menstrual history are assessed before randomization, on day 1 of course
4, and at 6, 12, 18, and 24 months. (Quality of life substudy closed to accrual as of

Patients are followed every 6 months for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 5,300 patients will be accrued for this study within 4-5

Inclusion Criteria


- Histologically confirmed invasive adenocarcinoma of the breast

- Confined to the breast and ipsilateral axilla on clinical exam

- Stage I, II, or IIIA (cT1-3, N0-1, M0)

- At least one axillary lymph node with evidence of tumor on histologic exam

- Sentinel node biopsy allowed if followed by axillary dissection

- No suspicious palpable nodes in the contralateral axilla or palpable
supraclavicular or infraclavicular nodes, unless proven on biopsy to not be
involved with tumor

- No bilateral malignancy or mass in the opposite breast, unless mass is histologically
proven to be benign

- Must have undergone either a prior total mastectomy and axillary dissection (modified
radical mastectomy) OR

- Prior lumpectomy and axillary dissection

- Patients must receive radiotherapy after randomization (not before) AND after

- Margins must be clear

- No ipsilateral lymph nodes that are fixed to one another or to other structures
(N2 disease) and/or any positive nonaxillary lymph nodes (intramammary nodes are
considered axillary nodes)

- No histologically evident invasive tumor or ductal carcinoma in situ

- No diffuse tumors by mammography that would not be surgically amenable to

- No other dominant mass in the ipsilateral breast remnant unless one of the
following is true:

- Histologically benign

- Surgically removed with clear margins if malignant

- No ulceration, erythema, infiltration of the skin or underlying chest wall (complete
fixation), peau d'orange, or skin edema of any magnitude

- Tethering or dimpling of the skin or nipple inversion allowed

- No metastatic disease

- Skeletal pain allowed if bone scan negative for metastases

- Hormone receptor status:

- Estrogen and progesterone status determined



- greater than or equal to 18 years


- Female

Menopausal status:

- Not specified

Performance status:

- Not specified

Life expectancy:

- At least 10 years, excluding diagnosis of cancer


- Absolute neutrophil count at least 1,500/mm^3 (may be less, if in the opinion of the
investigator, this represents an ethnic or racial variation)

- Platelet count at least 100,000/mm^3* NOTE: *If platelet count is above the upper
limit of normal (ULN), significant underlying hematologic disorders must be excluded


- Bilirubin no greater than ULN

- Alkaline phosphatase less than 2.5 times ULN*

- SGOT less than 1.5 times ULN*

- No nonmalignant systemic hepatic disease that would preclude study participation
NOTE: *Alkaline phosphatase and SGOT cannot both be greater than ULN


- Creatinine no greater than normal

- No nonmalignant systemic renal disease that would preclude study participation


- No nonmalignant systemic cardiovascular disease that would preclude study

- LVEF at least lower limit of normal (LLN) by MUGA or echocardiogram

- No active cardiac disease that would preclude use of doxorubicin or docetaxel,
including the following:

- Any prior myocardial infarction

- Angina pectoris requiring anti-anginal medication

- History of congestive heart failure

- Cardiac arrhythmia requiring medication

- Severe conduction abnormality

- Valvular disease with documented cardiac function compromise

- Cardiomegaly on chest x-ray or ventricular hypertrophy on EKG, unless LVEF at
least LLN

- Poorly controlled hypertension (diastolic greater than 100 mm/Hg)

- Hypertension well controlled by medication allowed


- No grade 2 or greater peripheral neuropathy

- No other prior malignancy within the past 5 years except:

- Effectively treated squamous cell or basal cell skin cancer

- Surgically treated carcinoma in situ of the cervix

- Segmentally resected lobular carcinoma in situ of the ipsilateral or
contralateral breast

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception

- No nonmalignant systemic disease that would preclude study participation

- No diabetes with morning fasting blood glucose of 200 mg/dL or greater

- No psychiatric or addictive disorders that would preclude informed consent

- No contraindication to corticosteroids that would preclude study participation


Biologic therapy:

- No prior immunotherapy for breast cancer


- No prior chemotherapy for breast cancer

- No prior anthracyclines or taxanes

- No other concurrent investigational chemotherapy

Endocrine therapy:

- No prior hormonal therapy for breast cancer

- No concurrent hormonal birth control methods or other hormonal therapy

- No concurrent raloxifene, including for osteoporosis

- Concurrent low-dose topical estrogen in the form of conjugated estrogen ring or
conjugated estrogen vaginal cream (dose no more than 0.3 mg or 1/8 of an applicator
applied vaginally 3 times a week) allowed


- See Disease Characteristics

- No prior radiotherapy for this malignancy


- See Disease Characteristics

- No more than 84 days since prior surgery for breast cancer (e.g., lumpectomy,
mastectomy, sentinel node biopsy, axillary dissection, or re-excision of lumpectomy


- No prior systemic therapy for this malignancy

- No concurrent medications that alter cardiac conduction (e.g., digitalis, beta
blockers, or calcium-channel blockers) for cardiac arrhythmia, angina, or congestive
heart failure (allowed if administered for other reasons [e.g., hypertension])

- Concurrent bisphosphonates allowed

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall Survival

Outcome Time Frame:

8 years

Safety Issue:


Principal Investigator

Norman Wolmark, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

NSABP Foundation, Inc.


United States: Federal Government

Study ID:




Start Date:

March 1999

Completion Date:

December 2012

Related Keywords:

  • Breast Cancer
  • stage I breast cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • Breast Neoplasms



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