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 chemotherapy with monoclonal antibody therapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of trastuzumab plus docetaxel in treating women who have recurrent or metastatic breast cancer.

Condition	Treatment or Intervention	Phase
stage IV breast cancer recurrent breast cancer	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: monoclonal antibody therapy  Procedure: antibody therapy  Drug: docetaxel  Drug: trastuzumab	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the objective response rate of women with HER2-neu overexpressing recurrent or metastatic breast cancer treated with trastuzumab (Herceptin) in combination with docetaxel. II. Determine the toxicity of this treatment regimen in these patients. III. Determine the duration of response to this treatment regimen in these patients. IV. Determine the time to progression in these patients after receiving this treatment regimen. V. Compare HER2-neu overexpression as determined by fluorescent in situ hybridization (FISH) versus immunohistochemistry, and correlate these findings with response to this treatment regimen in these patients. VI. Correlate HER2-neu activation by immunohistochemistry and the extracellular domain of HER2-neu by ELISA with response to this treatment regimen in these patients.

PROTOCOL OUTLINE: This is a multicenter study. Patients receive docetaxel IV over 30 minutes weekly for 6 weeks plus trastuzumab (Herceptin) IV over 30-90 minutes weekly for 8 weeks. Treatment continues every 8 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed monthly for 3 months, every 3 months for 9 months, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 18-34 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed recurrent or metastatic breast cancer; HER2-neu overexpressing tumor (2+ or 3+)
• Measurable or evaluable disease; If bone disease only, must have lytic lesions
• No carcinomatous meningitis or untreated or uncontrolled brain parenchymal disease
• Prior brain parenchymal disease allowed if controlled by appropriate therapy given at least 8 weeks prior to study, and patient is asymptomatic from CNS disease
• Hormone receptor status: Not specified

--Prior/Concurrent Therapy--

• Biologic therapy: No concurrent biologic response modifiers
• Chemotherapy: Prior adjuvant chemotherapy allowed; No more than 1 prior chemotherapy regimen for metastatic disease; No prior taxane (docetaxel or paclitaxel;) Prior doxorubicin allowed if total dose less than 250 mg/m2; No other concurrent chemotherapy
• Endocrine therapy: Prior hormonal therapy allowed; No concurrent hormonal therapy
• Radiotherapy: At least 4 weeks since prior radiotherapy; No prior cumulative radiotherapy to more than 25% of bone marrow; No concurrent radiotherapy
• Surgery: Not specified
• Other: At least 7 days since prior antibiotics; No other concurrent investigational drugs; No other concurrent antineoplastic therapy; No concurrent parenteral antibiotics

--Patient Characteristics--

• Age: 18 and over
• Sex: Female
• Menopausal status: Not specified
• Performance status: ECOG 0-2
• Life expectancy: Not specified
• Hematopoietic: WBC at least 3,000/mm3; Absolute neutrophil count at least 1,500/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin normal; Alkaline phosphatase no greater than 2.5 times upper limit of normal (ULN); SGOT and SGPT no greater than 1.5 times ULN
• Renal: Creatinine no greater than 2.0 mg/dL
• Cardiovascular: No congestive heart failure; Ejection fraction greater than 45% by MUGA; No myocardial infarction within the past 6 months; No ischemic heart disease requiring medication; No uncontrolled hypertension
• Other: No peripheral neuropathy grade 2 or more; No other prior malignancy within the past 5 years except curatively treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or contralateral breast cancer; No active unresolved infection; No history of hypersensitivity reaction to products containing Polysorbate 80; No poorly controlled diabetes mellitus; Not pregnant; Negative pregnancy test; Fertile patients must use effective contraception

Illinois
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611-3013,  United States
Pennsylvania
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111,  United States
Tennessee
      Vanderbilt-Ingram Cancer Center, Nashville,  Tennessee,  37232-6838,  United States

Study chairs or principal investigators

David Horton Johnson,  Study Chair,  Vanderbilt-Ingram Cancer Center   

Study ID Numbers:  CDR0000068114; VU-VCC-BRE-9823; NCI-G00-1830
Record last reviewed:  December 2003
Last Updated:  October 13, 2004
Record first received:  August 3, 2000
ClinicalTrials.gov Identifier:  NCT00006104
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08