S0215 Trastuzumab, Docetaxel, Vinorelbine, and Filgrastim in Treating Women With Stage IV Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Colony-stimulating factors, such as filgrastim, may help a person's immune system recover from the side effects of chemotherapy. PURPOSE: Phase II trial to study the effectiveness of combining trastuzumab with docetaxel, vinorelbine, and filgrastim in treating women who have stage IV breast cancer.

Detailed Description
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OBJECTIVES: Determine the 1-year survival of women with HER2-positive stage IV breast cancer treated with trastuzumab (Herceptin), docetaxel, and vinorelbine with filgrastim (G-CSF) support. Determine the response rate (complete and partial, confirmed and unconfirmed) in the subset of patients with measurable disease treated with this regimen. Determine the progression-free survival of patients treated with this regimen. Determine the qualitative and quantitative toxic effects of this regimen in these patients. Obtain tissue blocks for the determination of predictors of response (e.g., beta-tubulin mutations) to microtubule interacting agents in this patient population and for other future studies. OUTLINE: This is a pilot, multicenter study. Patients receive docetaxel IV over 1 hour on day 1, filgrastim (G-CSF) subcutaneously on days 2-21, vinorelbine IV over 6-10 minutes on days 8 and 15, and trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. If docetaxel and vinorelbine are discontinued due to unacceptable toxicity, patients may continue to receive trastuzumab. If trastuzumab is discontinued due to unacceptable toxicity, patients may continue to receive chemotherapy with G-CSF support. Patients are followed every 6 months for 3 years. PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study within 18-22.5 months.

Official Title
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Docetaxel (NSC-628503) And Vinorelbine (NSC-608210) Plus Filgrastim (NSC-614629) With Weekly Trastuzumab (NSC-688097) For HER-2 Positive, Stage IV Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: filgrastim
* Biological: trastuzumab
* Drug: docetaxel
* Drug: vinorelbine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed stage IV breast cancer Metastasis to the ipsilateral supraclavicular lymph nodes allowed HER2-positive by fluorescence in situ hybridization (FISH) or immunohistochemistry 3+ staining confirmed in the adjuvant or metastatic setting No effusions or ascites as only sites of disease No primary or metastatic brain or central nervous system tumor Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age: 18 and over Sex: Female Menopausal status: Not specified Performance status: Zubrod 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin normal aspartate aminotransferase or Alanine aminotranferease no greater than 1.5 times upper limit of normal (ULN) Alkaline phosphatase no greater than 2.5 times ULN Renal: Not specified Cardiovascular: left ventricular ejection fraction normal by multigated radionuclide angiography or echocardiogram (patients who have received prior anthracycline therapy) No clinical evidence or history of cardiomyopathy Other: No pre-existing grade 2 or greater motor or sensory peripheral neuropathy except abnormalities due to cancer No prior severe hypersensitivity reaction to docetaxel or other drugs formulated with Polysorbate 80 No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other adequately treated stage I or II cancer currently in complete remission No known sensitivity to E. coli-derived proteins Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 6 months since prior chemotherapy Prior anthracycline as adjuvant therapy allowed No prior cumulative dose of doxorubicin more than 360 mg/m^2 No prior cumulative dose of epirubicin more than 720 mg/m^2 No more than 1 prior adjuvant or neoadjuvant chemotherapy regimen for primary disease No prior docetaxel No prior vinorelbine Prior paclitaxel allowed Endocrine therapy: Prior hormonal therapy as adjuvant therapy or for metastatic breast cancer allowed No concurrent hormonal therapy Radiotherapy: At least 3 weeks since prior radiotherapy Surgery: At least 2 weeks since prior surgery and recovered

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trastuzumab, docetaxel, vinorelbine and filgrastim<br>Trastuzumab, docetaxel, vinorelbine and filgrastim | Biological: filgrastim<br> <br> Biological: trastuzumab<br> <br> Drug: docetaxel<br> <br> Drug: vinorelbine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival at 1 Year |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate (Complete and Partial, Confirmed and Unconfirmed) | Response was measured by the RECIST criteria. A patient was considered a responder if there was confirmed or unconfirmed partial or complete response. All others were considered non-responders even if the patient was technically not assessable due to different measurement techniques at the two time points. | response assessed after every 3 cycles (9 weeks) during treatment for up to 3 years if no progession | 
| Progression-free Survival |  | 2 years | 
| Toxicity | Number of patients for whom highest grade of toxicity observed during treatment. Only adverse events that are possibly, probably or definitely related to study drug are reported. | toxicities assessed every 3 weeks during treatment, for up to 3 years if no progession | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV breast cancer, recurrent breast cancer