RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which regimen of chemotherapy is more effective for breast cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of two different regimens of combination chemotherapy in treating women who have stage II or stage IIIA breast cancer that has spread to the lymph nodes.

Condition	Treatment or Intervention	Phase
Breast Cancer	Procedure: chemotherapy  Procedure: radiation therapy  Procedure: hormone therapy  Procedure: endocrine therapy  Procedure: antiestrogen therapy  Drug: cyclophosphamide  Drug: docetaxel  Drug: doxorubicin  Drug: paclitaxel  Drug: tamoxifen	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the disease-free survival and overall survival in patients with node-positive or high-risk node-negative operable stage II or IIIA breast cancer treated with docetaxel or paclitaxel after doxorubicin and cyclophosphamide. II. Determine whether the weekly administration of paclitaxel or docetaxel for 12 weeks improves disease-free survival and overall survival when compared with the conventional schedule of every 3 weeks for 4 courses after doxorubicin and cyclophosphamide in this patient population. III. Compare the toxic effects of docetaxel and paclitaxel when administered weekly for 12 weeks versus every 3 weeks for 4 courses in these patients. IV. Compare the toxicity of paclitaxel administered every 3 weeks for 4 courses or weekly for 12 weeks to that of docetaxel administered on the same schedules in these patients.

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are stratified according to estrogen receptor status (positive vs negative vs unknown), nodal status (0 positive nodes vs 1-3 positive nodes vs 4-9 positive nodes vs at least 10 positive nodes), tumor size (no more than 5 cm vs more than 5 cm vs unknown), and type of prior surgery (mastectomy vs breast conservation surgery). Patients are randomized to one of four treatment arms. Arm I: Patients receive doxorubicin IV and cyclophosphamide IV every 3 weeks for 4 courses (weeks 1-12). Beginning at week 13, patients receive paclitaxel IV over 3 hours every 3 weeks for 4 courses. Arm II: Patients receive doxorubicin and cyclophosphamide as in arm I. Beginning at week 13, patients receive paclitaxel IV over 1 hour weekly for 12 weeks. Arm III: Patients receive doxorubicin and cyclophosphamide as in arm I. Beginning at week 13, patients receive docetaxel IV over 1 hour every 3 weeks for 4 courses. Arm IV: Patients receive doxorubicin and cyclophosphamide as in arm I. Beginning at week 13, patients receive docetaxel IV over 1 hour weekly for 12 weeks. Within 4 weeks after completion of chemotherapy, patients with estrogen and/or progesterone receptor positive tumors receive oral tamoxifen daily for 5 years. After completion of all chemotherapy, patients with prior segmental mastectomy receive radiotherapy once daily 5 days per week for 5-6 weeks. Patients with prior modified radical mastectomy may receive radiotherapy after chemotherapy completion at the investigator's discretion. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 5,000 patients will be accrued for this study within 1.27 years.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed operable stage IIA, IIB, or IIIA adenocarcinoma of the breast with histologically involved lymph nodes (T1, 2, or 3; N1 or 2; M0) OR high-risk node-negative disease (T2 or 3; N0) Primary tumor at least 2.1 cm in diameter for node-negative disease Bilateral breast disease allowed if at least 1 primary tumor meets the criteria above
• Must have had at least 6 axillary lymph nodes removed at dissection and at least one node positive for metastasis OR Sentinel node biopsy negative for metastasis (sentinel node biopsy positive allowed if enrolled on American College of Surgery Trial Z0011 and have been randomized to receive no axillary dissection) Additional axillary nodes may be obtained provided they are also negative for metastasis
• Complete tumor removal by either a modified radical mastectomy or local excision plus axillary lymph node dissection (i.e., breast conservation therapy) or sentinel node biopsy Tumor-free margins at least 1 mm for both invasive and noninvasive carcinoma except for lobular carcinoma in situ (less than 1 mm allowed)
• Concurrent enrollment on American College of Surgery Trial Z0010, Z0011, or NSABP B-32 allowed
• Hormone receptor status: Estrogen receptor status positive, negative, or unknown

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior chemotherapy for breast cancer
• Endocrine therapy: Prior tamoxifen of no more than 4 weeks duration for breast cancer allowed Prior tamoxifen or other selective estrogen receptor modulator (SERM) for chemoprevention (e.g., Breast Cancer Prevention Trial) or for other indications (e.g., osteoporosis) allowed No concurrent tamoxifen or other SERMs
• Radiotherapy: No prior radiotherapy for this malignancy At least 2 weeks since prior radiotherapy to the breast for ductal carcinoma in situ
• Surgery: See Disease Characteristics Less than 84 days since prior surgical procedure to adequately treat primary tumor

--Patient Characteristics--

• Age: 18 and over
• Sex: Female
• Menopausal status: Not specified
• Performance status: Not specified
• Life expectancy: Not specified
• Hematopoietic: Neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than 1.5 mg/dL SGOT no greater than 2 times upper limit of normal
• Renal: Creatinine no greater than 1.5 mg/dL
• Cardiovascular: No history of myocardial infarction No congestive heart failure No significant ischemic or valvular heart disease
• Other: No other prior invasive malignancies within the past 5 years except curatively treated basal or squamous cell skin cancer or carcinoma in situ of the cervix No hypersensitivity to paclitaxel or docetaxel or other similarly formulated drugs (with Cremophor or polysorbate) Not pregnant or nursing Fertile patients must use effective barrier contraception

Alabama
      Veterans Affairs Medical Center - Birmingham, Birmingham,  Alabama,  35233-1996,  United States
California
      UCSF Cancer Center and Cancer Research Institute, San Francisco,  California,  94143-0128,  United States
      University of California San Diego Cancer Center, La Jolla,  California,  92093-0658,  United States
      Veterans Affairs Medical Center - San Francisco, San Francisco,  California,  94121,  United States
Delaware
      CCOP - Christiana Care Health Services, Wilmington,  Delaware,  19899,  United States
District of Columbia
      Lombardi Cancer Center, Washington,  District of Columbia,  20007,  United States
      Walter Reed Army Medical Center, Washington,  District of Columbia,  20307-5000,  United States
Florida
      CCOP - Mount Sinai Medical Center, Miami Beach,  Florida,  33140,  United States
Illinois
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States
Iowa
      Hematology Oncology Associates of the Quad Cities, Bettendorf,  Iowa,  52722,  United States
      Holden Comprehensive Cancer Center at The University of Iowa, Iowa City,  Iowa,  52242-1009,  United States
Maine
      Veterans Affairs Medical Center - Togus, Togus,  Maine,  04330,  United States
Maryland
      Marlene & Stewart Greenebaum Cancer Center, University of Maryland, Baltimore,  Maryland,  21201,  United States
Massachusetts
      Dana-Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
      University of Massachusetts Memorial Medical Center, Worcester,  Massachusetts,  01655,  United States
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States
      Veterans Affairs Medical Center - Minneapolis, Minneapolis,  Minnesota,  55417,  United States
Missouri
      Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States
      Ellis Fischel Cancer Center - Columbia, Columbia,  Missouri,  65203,  United States
      Veterans Affairs Medical Center - Columbia (Truman Memorial), Columbia,  Missouri,  65201,  United States
Nebraska
      University of Nebraska Medical Center, Omaha,  Nebraska,  68198-3330,  United States
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States
New Hampshire
      Norris Cotton Cancer Center, Lebanon,  New Hampshire,  03756-0002,  United States
New York
      CCOP - North Shore University Hospital, Manhasset,  New York,  11030,  United States
      CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., Syracuse,  New York,  13217,  United States
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
      Mount Sinai Medical Center, NY, New York,  New York,  10029,  United States
      New York Presbyterian Hospital - Cornell Campus, New York,  New York,  10021,  United States
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States
      Schneider Children's Hospital at North Shore, Manhasset,  New York,  11030,  United States
      State University of New York - Upstate Medical University, Syracuse,  New York,  13210,  United States
      Veterans Affairs Medical Center - Buffalo, Buffalo,  New York,  14215,  United States
      Veterans Affairs Medical Center - Syracuse, Syracuse,  New York,  13210,  United States
North Carolina
      CCOP - Southeast Cancer Control Consortium, Winston Salem,  North Carolina,  27104-4241,  United States
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States
      Lineberger Comprehensive Cancer Center, UNC, Chapel Hill,  North Carolina,  27599-7295,  United States
      Veterans Affairs Medical Center - Durham, Durham,  North Carolina,  27705,  United States
Ohio
      Arthur G. James Cancer Hospital - Ohio State University, Columbus,  Ohio,  43210-1240,  United States
Rhode Island
      Rhode Island Hospital, Providence,  Rhode Island,  02903,  United States
Tennessee
      University of Tennessee, Memphis Cancer Center, Memphis,  Tennessee,  38103,  United States
      Veterans Affairs Medical Center - Memphis, Memphis,  Tennessee,  38104,  United States
Vermont
      Green Mountain Oncology Group, Bennington,  Vermont,  05201,  United States
      Vermont Cancer Center, Burlington,  Vermont,  05401-3498,  United States
      Veterans Affairs Medical Center - White River Junction, White River Junction,  Vermont,  05009,  United States
Virginia
      MBCCOP - Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States
      Veterans Affairs Medical Center - Richmond, Richmond,  Virginia,  23249,  United States

Study chairs or principal investigators

Robert L. Comis,  Study Chair,  Eastern Cooperative Oncology Group   
Michael J. O'Connell,  Study Chair
Charles A. Coltman, Jr.,  Study Chair
Vicky Eileen Jones,  Study Chair

Study ID Numbers:  CDR0000067353; E-1199
Record last reviewed:  August 2003
Last Updated:  October 13, 2004
Record first received:  December 10, 1999
ClinicalTrials.gov Identifier:  NCT00004125
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08