RATIONALE: Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with combination chemotherapy may be an effective treatment for locally advanced breast cancer. PURPOSE: Phase I trial to study the effectiveness of trastuzumab plus paclitaxel followed by surgery and combination chemotherapy in treating women who have locally advanced breast cancer.

Condition	Treatment or Intervention	Phase
stage IIIB breast cancer stage IIIA breast cancer stage II breast cancer	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: surgery  Procedure: hormone therapy  Procedure: endocrine therapy  Procedure: antiestrogen therapy  Procedure: monoclonal antibody therapy  Procedure: antibody therapy  Procedure: conventional surgery  Drug: cyclophosphamide  Drug: doxorubicin  Drug: paclitaxel  Drug: tamoxifen  Drug: trastuzumab	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the safety and toxicity of preoperative trastuzumab (Herceptin) and paclitaxel followed by postoperative doxorubicin and cyclophosphamide in women with locally advanced breast cancer with HER2 overexpression. II. Determine tumor response in these patients treated with this regimen. III. Assess the effect of this regimen on tumor histology and the potential molecular determinants of response in these patients.

PROTOCOL OUTLINE: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes followed by paclitaxel IV over 60 minutes on day 1. Treatment continues every 7 days for a total of 10 courses in the absence of disease progression or unacceptable toxicity. Patients undergo a modified radical mastectomy or a lumpectomy with axillary node dissection. Beginning 14 days after surgery, patients receive doxorubicin IV and cyclophosphamide IV over 15-30 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses. After completion of chemotherapy, patients with hormone receptor-positive disease receive oral tamoxifen daily for 5 years. Patients are followed at 6 months.

PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Palpable primary breast cancer at least 3 cm (T2 at least 3 cm, T3-T4, any N)
• No distant metastasis (M0)
• HER2 overexpression of 2+ or 3+ by immunohistochemistry performed on core biopsy specimen using the Dako Hercep Test
• Hormone receptor status: Status known

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: Not specified
• Surgery: Not specified

--Patient Characteristics--

• Age: 18 and over
• Sex: Female
• Menopausal Status: Premenopausal or postmenopausal
• Performance status: ECOG 0-1
• Life expectancy: Not specified
• Hematopoietic: Absolute neutrophil count at least 1,500/mm3; Platelet count at least 150,000/mm3; Hemoglobin at least 10 g/dL
• Hepatic: Bilirubin no greater than 2.0 mg/dL; SGOT/SGPT no greater than 3 times normal
• Renal: Creatinine no greater than 2.0 mg/dL
• Cardiovascular: Ejection fraction normal by MUGA; No history of congestive heart failure, myocardial infarction, arrhythmia, or ischemic heart disease
• Other: No other prior malignancy except basal cell carcinoma of the skin or carcinoma in situ of the cervix; Not pregnant or nursing; Fertile patients must use effective barrier contraception during and for 2 months after study; No pre-existing clinically significant peripheral neuropathy

New York
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States

Study chairs or principal investigators

Matthew D. Volm,  Study Chair,  Kaplan Cancer Center   

Study ID Numbers:  CDR0000068430; NYU-9901; NCI-G00-1905; GENENTECH-NYU-9901
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  February 2, 2001
ClinicalTrials.gov Identifier:  NCT00009997
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08