Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Chemotherapy in Treating Women With Breast Cancer That Can Be Surgically Removed

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
NSABP Foundation Inc
ClinicalTrials.gov Identifier:
NCT00002707
First received: November 1, 1999
Last updated: February 2, 2010
Last verified: February 2010
  Purpose

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 if chemotherapy given before surgery is more effective with or without docetaxel given before or after surgery for breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy using doxorubicin and cyclophosphamide with or without docetaxel in treating women who have stage II or stage III breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: Cyclophosphamide
Drug: Docetaxel
Drug: Doxorubicin
Drug: Tamoxifen
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A RANDOMIZED TRIAL COMPARING PREOPERATIVE DOXORUBICIN (ADRIAMYCIN)/CYCLOPHOSPHAMIDE (AC) TO PREOPERATIVE AC FOLLOWED BY PREOPERATIVE DOCETAXEL (TAXOTERE) AND TO PREOPERATIVE AC FOLLOWED BY POSTOPERATIVE DOCETAXEL IN PATIENTS WITH OPERABLE CARCINOMA OF THE BREAST

Resource links provided by NLM:


Further study details as provided by NSABP Foundation Inc:

Primary Outcome Measures:
  • Determine if 4 cycle of pre-op or post-op Taxotere given after 4 cycles of pre-op AC will more effectively prolong survival (S) than does 4 cycles of pre-op AC alone. [ Time Frame: Time from randomization to death from any cause. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Prolonging disease-free survival (DFS). [ Time Frame: Time from randomization to first related event of inoperable disease; residual disease following surgery; local, regional or distant recurrence; second primary cancer; death from any cause other than cancer. ] [ Designated as safety issue: No ]
  • Clinical loco-regional tumor response to preoperative chemotherapy. [ Time Frame: 3-4 weeks after the last cycle of pre-op chemotherapy. ] [ Designated as safety issue: No ]
  • Pathologic loco-regional tumor response to pre-op chemotherapy. [ Time Frame: At time of surgery. ] [ Designated as safety issue: No ]
  • Breast conservation assessment. [ Time Frame: Assessed following surgery. ] [ Designated as safety issue: No ]
  • Evaluate if post-op Taxotere is of benefit in patients who received pre-op AC and, if so, whether it is of benefit in certain subgroups of patients. [ Time Frame: DFS and S will be assessed in patient subgroups. ] [ Designated as safety issue: No ]

Enrollment: 2411
Study Start Date: December 1995
Study Completion Date: February 2010
Primary Completion Date: June 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 2
doxorubicin and cyclophosphamide plus Taxotere prior to surgery plus tamoxifen
Drug: Cyclophosphamide
600 mg/m2 IV every 21 days for 4 cycles
Drug: Docetaxel
100 mg/m2 IV every 21 days for 4 cycles
Drug: Doxorubicin
60 mg/m2 IV every 21 days fo 4 cycles
Drug: Tamoxifen
20 mg p.o. once daily for 5 years starting on day 1 of ther first AC cycle
Experimental: Group 3
doxorubicin and cyclophosphamide followed by surgery followed by taxotere plus tamoxifen
Drug: Cyclophosphamide
600 mg/m2 IV every 21 days for 4 cycles
Drug: Docetaxel
100 mg/m2 IV every 21 days for 4 cycles
Drug: Doxorubicin
60 mg/m2 IV every 21 days fo 4 cycles
Drug: Tamoxifen
20 mg p.o. once daily for 5 years starting on day 1 of ther first AC cycle
Active Comparator: Group 1
doxorubicin and cyclophosphamide plus tamoxifen
Drug: Cyclophosphamide
600 mg/m2 IV every 21 days for 4 cycles
Drug: Doxorubicin
60 mg/m2 IV every 21 days fo 4 cycles
Drug: Tamoxifen
20 mg p.o. once daily for 5 years starting on day 1 of ther first AC cycle

Detailed Description:

OBJECTIVES: I. Compare overall and disease-free survival in patients with operable adenocarcinoma of the breast treated with 4 courses of preoperative doxorubicin and cyclophosphamide (AC) alone vs 4 courses of preoperative or postoperative docetaxel (TXT) following 4 courses of preoperative AC. II. Evaluate whether the addition of preoperative TXT to preoperative AC results in improved rates of clinical and pathologic locoregional tumor response. III. Assess whether the addition of preoperative TXT to preoperative AC results in improved rates of breast conservation. IV. Assess whether postoperative TXT improves disease-free and overall survival in patients who receive preoperative AC, especially in certain subgroups of patients (e.g., those with pathologically positive nodes).

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (under 50 vs 50 and over), clinical tumor size (less than 2.1 cm vs 2.1-4.0 cm vs greater than 4.0 cm), clinical nodal status (negative vs positive), and participating center. Patients are randomized to one of three treatment arms. Arm I: Patients receive doxorubicin IV followed by cyclophosphamide IV over 30 minutes to 2 hours on day 1 every 21 days for 4 courses. Patients receive oral tamoxifen daily for 5 years, starting on day 1. After completion of chemotherapy, patients are offered surgery (e.g., lumpectomy with axillary node dissection, or modified radical mastectomy). Post-operative radiotherapy is given post-lumpectomy. Arm II: Patients receive doxorubicin IV followed by cyclophosphamide IV over 30 minutes to 2 hours followed by docetaxel IV over 1 hour on day 1 once every 21 days for 4 courses. Patients receive oral tamoxifen daily for 5 years, starting on day 1. After the completion of chemotherapy, surgery is offered (as in arm I). Radiotherapy follows surgery in post-lumpectomy patients. Arm III: Patients receive doxorubicin IV followed by cyclophosphamide IV over 30 minutes to 2 hours on day 1 every 21 days for 4 courses. Patients receive oral tamoxifen daily for 5 years, starting on day 1. After completion of chemotherapy, surgery is offered (as in arm I). After surgical recovery, docetaxel IV is given over 1 hour once every 21 days for 4 courses. Radiotherapy follows docetaxel in post-lumpectomy patients. Chemotherapy is repeated every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 6 months for 5 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 2,400 patients will be accrued for this study within 5 years.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: Histologically or cytologically proven invasive adenocarcinoma of the breast Fine-needle aspiration is acceptable Core or Tru-cut biopsies are preferable No more than 63 days between initial diagnosis and randomization Tumor palpable on clinical exam and confined to the breast and ipsilateral axilla If clinically negative axillary nodes (N0): primary tumor greater than 1 cm (T1c-T3) If clinically positive axillary nodes (N1): any size primary tumor (T1-3) No N2 disease, i.e., ipsilateral nodes clinically fixed to one another or to other structures No skeletal pain unless: Bone scan and/or roentgenologic exam negative for metastatic disease Suspicious findings confirmed as benign by x-ray, MRI, or biopsy No ulceration, erythema, skin infiltration (complete fixation), or peau d'orange, or skin edema of any magnitude Tethering or dimpling of skin or nipple inversion allowed No bilateral malignancy Suspicious contralateral mass proven benign on biopsy allowed None of the following unless proven benign on biopsy: Suspicious palpable nodes in contralateral axilla Palpable supraclavicular or infraclavicular nodes Hormone receptor status: Any status

PATIENT CHARACTERISTICS: Age: Any age Sex: Female Menopausal status: Not specified Performance status: Not specified Life expectancy: At least 10 years (exclusive of cancer diagnosis) Hematopoietic: WBC at least 4,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin normal AST/ALT normal Alkaline phosphatase normal Renal: Creatinine normal Cardiovascular: No active cardiac disease that would preclude doxorubicin, e.g.: Documented myocardial infarction History of congestive heart failure Angina pectoris requiring medication Valvular disease with documented cardiac function compromise Arrhythmia associated with heart failure or cardiac dysfunction Poorly controlled hypertension, i.e., diastolic blood pressure greater than 100 mm Hg Cardiomegaly on chest x-ray or ventricular hypertrophy on EKG unless left ventricular ejection fraction at least 45% by MUGA Other: No other malignancy within the past 10 years except: Segmentally resected lobular carcinoma in situ of the ipsilateral or contralateral breast Effectively treated nonmelanomatous skin cancer Surgically treated carcinoma in situ of the cervix No systemic disease that would preclude therapy No psychiatric or addictive disorder that would preclude informed consent Geographically accessible for follow-up Not pregnant

PRIOR CONCURRENT THERAPY: No prior therapy for breast cancer No prior anthracyclines for any malignancy No concurrent sex hormones (e.g., birth control pills or ovarian replacement therapy)

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002707

  Show 145 Study Locations
Sponsors and Collaborators
NSABP Foundation Inc
Investigators
Study Chair: Harry D. Bear, MD, PhD Massey Cancer Center
  More Information

Additional Information:
Publications:
Julian T, Anderson S, Fourchotte V, et al.: Is invasive lobular breast cancer a prognostic factor for neoadjuvant chemotherapy response and long term outcomes? [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-3065, S146, 2006.
Bear HD, Anderson S, Smith RE, et al.: A randomized trial comparing preoperative (preop) doxorubicin/cyclophosphamide (AC) to preop AC followed by preop docetaxel (T) and to preop AC followed by postoperative (postop) T in patients (pts) with operable carcinoma of the breast: results of NSABP B-27. [Abstract] Breast Cancer Res Treat 88 (Suppl 1): A-26, 2004.
Mamounas EP, Brown A, Smith R, et al.: Accuracy of sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: updated results from NSABP B-27. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-140, 2002.

Responsible Party: Norman Wolmark, MD, NSABP Foundation, Inc.
ClinicalTrials.gov Identifier: NCT00002707     History of Changes
Other Study ID Numbers: NSABP B-27, CDR0000064521
Study First Received: November 1, 1999
Last Updated: February 2, 2010
Health Authority: United States: Federal Government

Keywords provided by NSABP Foundation Inc:
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Cyclophosphamide
Docetaxel
Doxorubicin
Liposomal doxorubicin
Tamoxifen
Alkylating Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Bone Density Conservation Agents
Enzyme Inhibitors
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014