RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzuman can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Paclitaxel may stop the growth of breast cancer by stopping blood flow to the tumor. PURPOSE: Phase II trial to compare the effectiveness of paclitaxel with or without trastuzumab following peripheral stem cell transplantation in treating patients who have refractory stage IV breast cancer.

Condition	Treatment or Intervention	Phase
stage IV breast cancer recurrent breast cancer	Drug: paclitaxel  Drug: trastuzumab	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the toxicity of paclitaxel with or without trastuzumab following high dose chemotherapy with autologous or syngeneic peripheral blood stem cell transplantation in patients with stage IV breast cancer. II. Assess the overall survival of these patients.

PROTOCOL OUTLINE: Patients begin study treatment within 50-150 days after autologous or syngeneic peripheral blood stem cell transplantation. Patients are stratified according to overexpression of HER2-Neu (yes vs no), which determines the type of therapy. Arm I (overexpression of HER2-Neu): Patients receive paclitaxel IV over 60 minutes followed by the initial loading dose of trastuzumab IV over 90 minutes. If the loading dose is tolerated well, then patients receive maintenance trastuzumab IV over 30 minutes. Treatment with paclitaxel followed by maintenance trastuzumab repeats once every week for 12 weeks in the absence of disease progression or unacceptable toxicity. Arm II (no overexpression of Her2-Neu): Patients receive paclitaxel IV over 60 minutes once every week for 12 weeks. Patients with hormone receptor positive disease also receive antihormonal therapy (tamoxifen or anastrozole) as clinically indicated. Patients with isolated metastasis such as a single bone lesion may receive radiotherapy to that site after completion of study treatment. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 60 patients (30 per arm) will be accrued for this study over 2-3 years.

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Refractory stage IV breast cancer; Received high dose chemotherapy (HDC) with autologous or syngeneic peripheral blood stem cell transplantation (PBSCT) OR Stage IV breast cancer; Failed to achieve complete response to HDC with autologous or syngeneic PBSCT at initial restaging following HDC
• No enrollment on protocol FHCRC-976, unless evidence of no response or progressive disease at initial restaging following transplantation
• Hormone receptor status: Not specified

--Prior/Concurrent Therapy--

• Biologic therapy: See Disease Characteristics
• Chemotherapy: See Disease Characteristics
• Endocrine therapy: Concurrent antihormonal therapy (tamoxifen or anastrozole) allowed as clinically indicated for hormone receptor positive disease
• Radiotherapy: Not specified
• Surgery: Not specified

--Patient Characteristics--

• Age: Not specified
• Menopausal status: Not specified
• Performance status: Karnofsky 70-100%
• Life expectancy: Not specified
• Hematopoietic: Platelet count at least 50,000/mm3 (untransfused); Absolute neutrophil count greater than 1,000/mm3 (without filgrastim (G-CSF) support)
• Hepatic: Bilirubin no greater than 2.5 times upper limit of normal (ULN); SGOT no greater than 2.5 times ULN
• Renal: Creatinine no greater than 2.0 mg/dL
• Cardiovascular: LVEF greater than 40%; No poorly controlled arrhythmias; No prior coronary artery disease; No congestive heart failure within last year; No myocardial infarction within past 2 years
• Other: No active infection; No grade 3 regimen related toxicity according to Bearman model; No allergy to paclitaxel, trastuzumab, or benzyl alcohol; No grade 3 peripheral neuropathy with last chemotherapy; HIV negative; Not pregnant or nursing; Fertile patients must use effective contraception

Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109,  United States

Study chairs or principal investigators

Leona Holmberg,  Study Chair,  Fred Hutchinson Cancer Research Center   

Study ID Numbers:  CDR0000067230; FHCRC-1338.00; NCI-G99-1557; GENENTECH-FHCRC-1338.00
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00004013
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08