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Combination Chemotherapy in Treating Women With Stage I, Stage II, or Stage IIIA (cT1-3, N0-1, M0) Breast Cancer and Positive Axillary Lymph Nodes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00003782
Recruitment Status : Completed
First Posted : January 27, 2003
Results First Posted : October 31, 2012
Last Update Posted : January 18, 2013
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NSABP Foundation Inc

Tracking Information
First Submitted Date  ICMJE November 1, 1999
First Posted Date  ICMJE January 27, 2003
Results First Submitted Date  ICMJE August 24, 2012
Results First Posted Date  ICMJE October 31, 2012
Last Update Posted Date January 18, 2013
Study Start Date  ICMJE March 1999
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 2, 2012)
  • Overall Survival [ Time Frame: 8 years ]
  • Disease Free Survival [ Time Frame: time to event: breast cancer recurrence; second primary cancer; death from any cause as a first event ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 2, 2009)
  • Toxicities Among the 3 Regimens [ Time Frame: 9 years ]
  • Quality of Life Among Breast Cancer Patients [ Time Frame: baseline, 9 weeks, and 6, 12, 18, and 24 months ]
  • Amenorrhea in Premenopausal Women [ Time Frame: baseline, 9 weeks, and 6, 12, 18, and 24 months ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Chemotherapy in Treating Women With Stage I, Stage II, or Stage IIIA (cT1-3, N0-1, M0) Breast Cancer and Positive Axillary Lymph Nodes
Official Title  ICMJE 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
Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving combination chemotherapy after surgery may kill any tumor cells remaining following surgery. It is not yet known which regimen of combination chemotherapy is more effective in treating breast cancer with positive axillary lymph nodes.

PURPOSE: Randomized phase III trial to compare the effectiveness of different regimens of combination chemotherapy in treating women who have undergone surgery for stage I, stage II, or stage IIIA breast cancer with positive axillary lymph nodes.

Detailed Description

OBJECTIVES:

  • 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 7/20/01.)

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 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: cyclophosphamide
    Arm 1: 600 mg/m2 IV every 21 days for 4 cycles; Arm 3: 500 mg/m2 IV every 21 days for 4 cycles
  • Drug: docetaxel
    Arm 1: 100 mg/m2 IV every 21 days for 4 cycles; Arms 2 and 3: 75 mg/m2 IV every 21 days for 4 cycles
    Other Name: Taxotere
  • Drug: doxorubicin
    Arm 1: 60 mg/m2 IV every 21 days for 4 cycles; Arms 2 and 3: 50 mg/m2 IV every 21 days for 4 cycles
    Other Name: Adriamycin
Study Arms  ICMJE
  • Experimental: Arm 1: Doxorubicin + Cyclophosphamide, then Docetaxel
    Doxorubicin + Cyclophosphamide, then Docetaxel
    Interventions:
    • Drug: cyclophosphamide
    • Drug: docetaxel
    • Drug: doxorubicin
  • Experimental: Arm 2: Doxorubicin + Docetaxel
    Doxorubicin + Docetaxel
    Interventions:
    • Drug: docetaxel
    • Drug: doxorubicin
  • Experimental: Arm 3: Doxorubicin + Docetaxel + Cyclophosphamide
    Doxorubicin + Docetaxel + Cyclophosphamide
    Interventions:
    • Drug: cyclophosphamide
    • Drug: docetaxel
    • Drug: doxorubicin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 2, 2009)
5351
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE December 2012
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • 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 chemotherapy
    • 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 lumpectomy
    • 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

PATIENT CHARACTERISTICS:

Age:

  • greater than or equal to 18 years

Sex:

  • Female

Menopausal status:

  • Not specified

Performance status:

  • Not specified

Life expectancy:

  • At least 10 years, excluding diagnosis of cancer

Hematopoietic:

  • 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

Hepatic:

  • 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

Renal:

  • Creatinine no greater than normal
  • No nonmalignant systemic renal disease that would preclude study participation

Cardiovascular:

  • No nonmalignant systemic cardiovascular disease that would preclude study participation
  • 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

Other:

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior immunotherapy for breast cancer

Chemotherapy:

  • 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

Radiotherapy:

  • See Disease Characteristics
  • No prior radiotherapy for this malignancy

Surgery:

  • 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 margins)

Other:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00003782
Other Study ID Numbers  ICMJE NSABP B-30
CDR0000066914
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party NSABP Foundation Inc
Study Sponsor  ICMJE NSABP Foundation Inc
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Norman Wolmark, MD NSABP Foundation Inc
PRS Account NSABP Foundation Inc
Verification Date January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP