Epirubicin, Docetaxel, and Capecitabine in Treating Women With Stage IIIA or Stage IIIB Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as epirubicin, docetaxel, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase II trial is studying the side effects of giving epirubicin together with docetaxel and capecitabine and to see how well it works in treating women with stage IIIA or stage IIIB breast cancer.

Detailed Description
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OBJECTIVES: Primary Describe the pathologic response rate in chemotherapy-naive women with locally advanced breast cancer (stage IIIA or IIIB) after 6 courses of sequential neoadjuvant therapy with epirubicin hydrochloride and a combination of docetaxel with capecitabine . Describe the adverse events of sequential epirubicin hydrochloride and a combination of docetaxel with capecitabine in this patient population. Secondary Identify by transcriptional profiling the differential expression of candidate gene products that confer chemosensitivity to epirubicin hydrochloride, docetaxel, and capecitabine. Correlate the differential expression of known genetic polymorphisms of intracellular regulators involved in the metabolism of epirubicin hydrochloride, docetaxel, and capecitabine with adverse events and tumor response. Assess individual patient variation in clinical (toxicity and/or activity), in pharmacologic (pharmacokinetic/pharmacodynamic parameters), and/or biologic (correlative laboratory study results) responses to epirubicin hydrochloride, docetaxel, and capecitabine due to genetic differences in proteins involved in drug response (transport, metabolism and/or mechanism of action). OUTLINE: Patients receive epirubicin hydrochloride IV on day 1. Treatment repeats every 2 weeks for 3 courses. Beginning 2 weeks after last dose of epirubicin hydrochloride, patients receive docetaxel IV over 1 hour on day 1 and oral capecitabine twice daily on days 1-14. Treatment with docetaxel and capecitabine repeats every 3 weeks for 3 courses. Patients then undergo surgery. Blood samples are collected at baseline for pharmacogenetic studies. Tumor tissue samples are collected at baseline and periodically during treatment for correlative laboratory studies. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.

Official Title
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A Neo-Adjuvant Study of Sequential Epirubicin and Docetaxel in Combination With Capecitabine in Patients With Locally Advanced Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: capecitabine
* Drug: docetaxel
* Drug: epirubicin hydrochloride
* Other: laboratory biomarker analysis
* Other: pharmacogenomic studies
* Procedure: biopsy
* Procedure: neoadjuvant therapy
* Procedure: therapeutic surgical procedure


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed breast cancer Stage IIIA or IIIB disease (T3 N1 M0, T4 N1 M0, any T N2/N3 M0) Bidimensionally measurable or evaluable disease Hormone receptor status not specified PATIENT CHARACTERISTICS: Menopausal status not specified ECOG performance status 0-2 Platelet count ≥ 100,000 cells/μL Total bilirubin normal Hemoglobin ≥ 8.0 g/dL ANC ≥ 1,000 cells/μL AST and ALT ≤ 2.5 times upper limit of normal Creatinine clearance ≥ 50 mL/min and serum creatinine normal Life expectancy ≥ 3 months No uncontrolled infection No chronic debilitating disease No lack of physical integrity of the upper gastrointestinal tract Able to swallow tablets No malabsorption syndrome No clinically significant cardiac disease not well controlled with medication (e.g., congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias [New York Heart Association class III-IV heart disease] or myocardial infarction within the last 12 months) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer or adequately treated other noninvasive carcinomas No peripheral neuropathy ≥ grade 1 PRIOR CONCURRENT THERAPY: More than 4 weeks since prior major surgery and recovered No prior chemotherapy regimens including adjuvant therapy No organ allograft No concurrent sorivudine or bruvidine No other concurrent cytostatic, cytotoxic, immunomodulating agents, or radiotherapy

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: capecitabine|nan|
|Drug: docetaxel|nan|
|Drug: epirubicin hydrochloride|nan|
|Other: laboratory biomarker analysis|nan|
|Other: pharmacogenomic studies|nan|
|Procedure: biopsy|nan|
|Procedure: neoadjuvant therapy|nan|
|Procedure: therapeutic surgical procedure|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic response rate |  |  | 
| Toxicity patterns |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer