Epirubicin and Cyclophosphamide Followed By Docetaxel and Trastuzumab in Treating Women With HER2-Positive Stage III or Stage IV Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as epirubicin, cyclophosphamide, and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving chemotherapy and a monoclonal antibody before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II trial is studying how well giving epirubicin and cyclophosphamide followed by docetaxel and trastuzumab works in treating women with HER2-positive stage IIIB, stage IIIC, or stage IV primary breast cancer.

Detailed Description
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OBJECTIVES: Primary Determine the pathological complete response in women with HER2-positive stage IIIB-IV breast cancer treated with neoadjuvant epirubicin hydrochloride and cyclophosphamide followed by docetaxel and trastuzumab (Herceptin®). Secondary Determine the clinical response in patients treated with this regimen. Determine the recurrence-free survival of patients treated with this regimen. Determine the overall survival of patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive epirubicin hydrochloride and cyclophosphamide in weeks 1-3. Treatment with epirubicin hydrochloride and cyclophosphamide repeats every 3 weeks for 4 courses. Patients then receive docetaxel in week 13 and trastuzumab (Herceptin®) in weeks 13-15. Treatment with docetaxel and trastuzumab repeats every 3 weeks for 4 courses. Patients then undergo appropriate surgery. After surgery, patients with hormone receptor-positive disease receive trastuzumab once weekly and either tamoxifen with or without a luteinizing hormone-releasing hormone agonist or an aromatase inhibitor. Treatment continues for 40 weeks. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Official Title
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Neoadjuvant Epirubicin/Cyclophosphamide Followed by Docetaxel Combined With Trastuzumab for the Patients With HER-Positive Advanced Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: trastuzumab
* Drug: cyclophosphamide
* Drug: docetaxel
* Drug: epirubicin hydrochloride
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of primary breast cancer Stage IIIB, IIIC, or IV disease No inflammatory disease HER2 over-expressing tumor as assessed by immunohistochemistry and/or fluorescent in situ hybridization Hormone receptor status known PATIENT CHARACTERISTICS: Female Menopausal status not specified Performance status 0-1 WBC ≤ 10,000/mm³ Absolute neutrophil count ≥ 2,000/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 9.5 g/dL SGOT/SGPT ≤ 60 IU/L Bilirubin ≤ 1.5 mg/dL Creatinine ≤ 1.5 mg/dL LVEF ≥ 55% No signs of pneumonitis PRIOR CONCURRENT THERAPY: No prior surgery except for biopsy No prior or concurrent chemotherapy and/or hormonal therapy No prior or concurrent biological therapy No prior or concurrent radiotherapy except postoperative radiotherapy

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 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: HER2 over-expressing primary breast cancer group<br>Patients receive epirubicin hydrochloride and cyclophosphamide in week 1-3. Treatment with epirubicin hydrochloride and cyclophosphamide repeats every 3 weeks for 4 courses. Patients then receive docetaxel in week 13 and trastuzumab (Herceptin®) in weeks 13-15. Treatment with docetaxel and trastuzumab repeats every 3 weeks for 4 courses. Patients then undergo appropriate surgery. After surgery, patients with hormone receptor-positive disease receive trastuzumab once weekly and either tamoxifen with or without a luteinizing hormone-releasing hormone agonist or an aromatase inhibitor. Treatment continues for 40 weeks. | Biological: trastuzumab<br> <br> Drug: cyclophosphamide<br> <br> Drug: docetaxel<br> <br> Drug: epirubicin hydrochloride<br> <br> Procedure: conventional surgery<br> <br> Procedure: neoadjuvant therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response | Pathological complete response is assessed in surgical resected specimens of primary tumor from patients who underwent a primary radical surgery in this study. | Whitin the first 7-28 days after the last administration of neoadjuvant therapy of trastuzumab | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response | Clinical response is assessed as overall response in target lesion of primary tumor from 7 days after the last administration of neoadjuvant therapy of Trastuzumab until surgery. | From 7 days after the last adoministration of neosdjuvant therapy of Trastuzumab until surgery. | 
| Pathological response of axillary lymph nodes | Pathological response of axillary lymph nodes is assessed in surgical specimens of primary tumor from patients who underwent a primary radical surgery in this study. | Whitin the first 7-28 days after the last administration of neoadjuvant therapy of trastuzumab. | 
| Recurrence-free survival | Recurrence-free survival is defined as time from date of enrollment until date of recurrence or death from any cause, whichever comes first. | 8 years | 
| Overall survival | Overall survival is defined as time from date of enrollment until date of death from any cause. | 8 years | 
| Adverse event | Types and severities of adverse events from date of starting protocol treatment until 30 days after date of finishing the treatment are evaluated according to Japanese version of the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) by Translational Research Informatics Center. | 70 months | 

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