Epirubicin and Docetaxel Combination (ET) or Epirubicin Followed by Docetaxel (E/T) for Node Negative (N0) High Risk Breast Cancer Patients

Study Overview
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Brief Summary
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The combination of taxanes, and especially docetaxel, with an anthracycline seems to be an important part of the chemotherapy regimens used in the adjuvant setting of patients with early-stage node-positive breast cancer patients. Whether sequential or concurrent administration of these drugs is preferable is not yet known, especially in patients with node-negative high risk tumors.

Official Title
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A Multicenter Randomized Phase III Study of Adjuvant Treatment With Epirubicin Followed by Docetaxel (E/T) Versus Epirubicin and Docetaxel Combination (ET) in High Risk Lymph Node Negative Breast Cancer Patients

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Epirubicin
* Drug: Epirubicin
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed breast adenocarcinoma. Within 20-45 days after the surgical excision of the primary tumor with tumor-free operation margins; at least 10 axillary lymph nodes have to be removed. Absence of lymph node involvement after eclosion and hormone (E&H) staining and light microscopy evaluation. Premenopausal or postmenopausal women with at least one of the following tumor characteristics is required in order to characterize the tumor as high risk: Estrogen receptor (ER) (-) and progesterone receptor (PR)(-); Ki-67 + > 30%; Grade III; HER2 (3+) (after an amendment on 15.05.2008 women with HER2 (3+) were not included); Perineural infiltration or presence of tumor emboli in blood or lymph vessels. Postmenopausal women with tumors 1-2 cm are eligible if the tumor has at least 2 of the above mentioned high risk criteria. Premenopausal and postmenopausal women with tumors measuring > 2 cm are eligible irrespectively of the expression of the above adverse prognostic tumor criteria. Absence of any clinical or radiological evidence of local or metastatic disease. Age > 18 years. Performance status (WHO) < 3. Adequate bone marrow function (absolute neutrophil count > 1000/mm^3, platelet count > 100000/mm^3, hemoglobin > 9 gr/mm^3). Adequate liver (bilirubin < 1.5 times upper limit of normal and SGOT/SGPT < 2 times upper limit of normal) and renal function (creatinine < 2 mg/dl). Adequate cardiac function (LVEF > 50%). Negative pregnancy test. Informed consent. Exclusion Criteria: Other invasive malignancy within the past 5 years except nonmelanoma skin cancer. Other concurrent uncontrolled illness that could affect compliance with the study. Psychiatric illness or social situation that would preclude study compliance. Pregnant or nursing women. History of allergic reaction attributed to docetaxel. Other concurrent investigational agents.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Docetaxel<br>* Docetaxel at the dose of 75 mg/m2 intravenously (IV) every 3 weeks for 4 consecutive cycles<br>* Other names: Taxotere;Drug: Epirubicin<br>* Epirubicin at the dose of 90 mg/m2 IV every 3 weeks for 4 consecutive cycles<br>* Other names: Farmorubicin;|
| Experimental: 2<br> | Drug: Epirubicin<br>* Epirubicin at the dose of 75 mg/m2 IV every 3 weeks for 6 consecutive cycles<br>* Other names: Farmorubicin;Drug: Docetaxel<br>* Docetaxel at the dose of 75 mg/m2 IV every 3 weeks for 6 consecutive cycles<br>* Other names: Taxotere;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free interval between the two treatment arms |  | Five years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of overall survival and safety between the two treatment arms |  | Five years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High risk node negative