Sequential Administration of FE75C and Docetaxel Versus Docetaxel/Cyclophosphamide in HER-2 Negative, Node Positive Breast Cancer

Study Overview
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Brief Summary
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In this trial investigators propose to assess the dose dense, G-CSF supported sequential administration of 4 cycles of FEC followed by 4 cycles of docetaxel versus 6 cycles of docetaxel/cyclophosphamide as adjuvant chemotherapy in women with HER-2 negative, axillary lymph node positive breast cancer

Detailed Description
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Anthracycline-containing regimens are recommended as adjuvant treatment for women with node positive breast cancer. At least five large randomized clinical trials demonstrated that the addition or sequential administration of a taxane (paclitaxel or docetaxel) to an anthracycline-based regimen resulted in superior clinical outcome for women with node positive or high risk node-negative early breast cancer. In two large randomized studies the dose dense administration with G-CSF support of anthracycline-based and paclitaxel combination was superior to the same regimen administered every three weeks without growth factors as adjuvant therapy in women with axillary node positive breast cancer. In one randomized trial, docetaxel was proved superior to paclitaxel in women with metastatic breast cancer. Data from at least one trial suggest that four cycles of a non-anthracycline but taxane-containing adjuvant regimen (docetaxel plus cyclophosphamide) provide outcomes that are at least as good, if not better than four cycles of doxorubicin/cyclophosphamide combination.

Official Title
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A Multicenter Randomized Study Comparing the Dose Dense, G-CSF-supported Sequential Administration of FE75C Followed by Docetaxel Versus Docetaxel/Cyclophosphamide Doublet as Adjuvant Chemotherapy in Women With HER-2 Negative, Axillary Lymph Node Positive Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Epirubicin
* Drug: Cyclophosphamide
* Drug: 5-fluoruracil
* Drug: Granulocyte-colony stimulating growth factor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with histologically-confirmed unilateral invasive ductal or lobular breast adenocarcinoma Within 60 days after the surgical excision of the primary tumor with tumor-free operation margins; at least 10 axillary lymph nodes have to be removed. Tumor involvement of at least one axillary lymph node Absence of any clinical or radiological evidence of local or metastatic disease Premenopausal or postmenopausal women aged 18-75 years old Adequate bone marrow function (absolute neutrophil count >1500/mm3, platelet count >100.000/mm3, hemoglobin >10gr/mm3) Adequate liver (bilirubin <1.0 times upper limit of normal and SGOT/SGPT <2.5 times upper limit of normal) and renal function (creatinine <1.5mg/dl) Adequate cardiac function (LVEF>50%) Written informed consent Exclusion Criteria: Positive pregnancy test. Psychiatric illness or social situation that would preclude study compliance. Other concurrent uncontrolled illness. Prior or concurrent antineoplastic therapy e.g. hormonal therapy, radiation therapy, chemotherapy, biological agents. Previous history of other invasive malignancy other than non-melanomatous skin cancer.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>FEC -> TXT | Drug: Docetaxel<br>* ARM A: Docetaxel 75 mg/m2 as an IV infusion over 1h on day 1 every 2 weeks for 4 cycles ARM B: Docetaxel 75 mg/m2 as an IV infusion over 1h on day 1 every 3 weeks for 6 cycles<br>* Other names: Taxotere;Drug: Epirubicin<br>* ARM A: Epirubicin 75 mg/m2 IV push on day 1 every 2 weeks for 4 cycles<br>* Other names: Farmorubicin;Drug: Cyclophosphamide<br>* ARM A: Cyclophosphamide 500 mg/m2 IV push on day 1 every 2 weeks for 4 cycles ARM B: Cyclophosphamide 600 mg/m2 IV push on day 1 every 3 weeks for 6 cycles<br>* Other names: Endoxan;Drug: 5-fluoruracil<br>* ARM A: 5-fluoruracil 500 mg/m2 IV push on day 1 every 2 weeks for 4 cycles<br>* Other names: 5-FU;Drug: Granulocyte-colony stimulating growth factor<br>* rhG-CSF 5 μg/kg/d on days 3-10 after each cycle<br>* Other names: Neulasta;|
| Experimental: B<br>Docetaxel/Cyclophosphamide (TC) | Drug: Docetaxel<br>* ARM A: Docetaxel 75 mg/m2 as an IV infusion over 1h on day 1 every 2 weeks for 4 cycles ARM B: Docetaxel 75 mg/m2 as an IV infusion over 1h on day 1 every 3 weeks for 6 cycles<br>* Other names: Taxotere;Drug: Cyclophosphamide<br>* ARM A: Cyclophosphamide 500 mg/m2 IV push on day 1 every 2 weeks for 4 cycles ARM B: Cyclophosphamide 600 mg/m2 IV push on day 1 every 3 weeks for 6 cycles<br>* Other names: Endoxan;Drug: Granulocyte-colony stimulating growth factor<br>* rhG-CSF 5 μg/kg/d on days 3-10 after each cycle<br>* Other names: Neulasta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year disease-free survival |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 3 years | 
| Recurrence rate |  | Relapses by the time of 3-years follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Early breast cancer, Axillary node positive, HER-2 negative, Adjuvant chemotherapy, Dose dense, Docetaxel, FEC