Neoadjuvant Epirubicin, Cyclophosphamide, and Paclitaxel With or Without Gemcitabine in Treating Women Who Are Undergoing Surgery for Early Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as epirubicin, cyclophosphamide, paclitaxel, and gemcitabine use different ways to stop tumor cells from dividing so they stop growing or die. Giving combination chemotherapy before surgery may shrink the tumor so that it can be removed during surgery. It is not yet known which combination chemotherapy regimen is more effective in treating early breast cancer. PURPOSE: This randomized phase III trial is studying different regimens of combination chemotherapy to compare how well they work in treating women who are undergoing surgery for early invasive breast cancer.

Detailed Description
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OBJECTIVES: Primary Compare the complete pathological response rate in women with poor-risk early breast cancer treated with neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel with vs without gemcitabine. Secondary Compare the disease-free and overall survival of patients treated with these regimens. Compare the toxicity of these regimens in these patients. Compare the effect of these regimens on prognostic factors in these patients. Correlate molecular profiles, specific gene mutations, and genomic and gene expression changes with clinical outcome in these patients. Compare the quality of life of patients treated with these regimens. Determine the health economics associated with this study. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to estrogen-receptor status (negative vs greater than 10% positive cells), HER-2 status (positive vs negative), tumor size (30-50 mm vs greater than 50 mm), and clinical involvement of axillary nodes (yes vs no). Patients are randomized to 1 of 4 treatment arms. Neoadjuvant sequential chemotherapy: Arm I: Patients receive epirubicin IV and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients then receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for 4 courses. Arm II: Patients receive paclitaxel as in arm I followed by epirubicin and cyclophosphamide as in arm I. Arm III: Patients receive epirubicin and cyclophosphamide as in arm I followed by paclitaxel as in arm I and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 4 courses. Arm IV: Patients receive paclitaxel as in arm I and gemcitabine as in arm III followed by epirubicin and cyclophosphamide as in arm I. Surgery: After completion of neoadjuvant chemotherapy, patients in all arms undergo definitive surgery. Tumor tissue is removed from a subset of patients during serial biopsies. Molecular and genetic profiling, mutation analysis, and comparative genomic analysis is performed on the tissue samples. Quality of life is assessed at baseline, after 4 courses of chemotherapy, after the completion of chemotherapy, after surgery, and then every 6 months for 2 years. Patients are followed every 2 months for 2 years and then every 3 months for 3 years. Peer Reviewed and Funded or Endorsed by Cancer Research UK PROJECTED ACCRUAL: A total of 800 patients (200 per treatment arm) will be accrued for this study.

Official Title
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A Phase III Randomized Neoadjuvant Study of Sequential Epirubicin/Cyclophosphamide and Paclitaxel + - Gemcitabine in Poor Risk Early Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: cyclophosphamide
* Drug: epirubicin hydrochloride
* Drug: gemcitabine hydrochloride
* Drug: paclitaxel
* Genetic: comparative genomic hybridization
* Genetic: microarray analysis
* Genetic: mutation analysis
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed invasive breast cancer Grade 2 or 3 Tumor size at least 3 cm by ultrasound No evidence of metastatic disease Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age Not specified Sex Female Menopausal status Not specified Performance status Not specified Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Fit to receive study chemotherapy PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified
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
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cyclophosphamide|nan|
|Drug: epirubicin hydrochloride|nan|
|Drug: gemcitabine hydrochloride|nan|
|Drug: paclitaxel|nan|
|Genetic: comparative genomic hybridization|nan|
|Genetic: microarray analysis|nan|
|Genetic: mutation analysis|nan|
|Procedure: conventional surgery|nan|
|Procedure: neoadjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete pathological response after 4 courses |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  |  | 
| Disease-free survival |  |  | 
| Effect of prognostic factors |  |  | 

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