Randomized Phase III Trial Comparing Sequential Administration of FE75C Followed by Docetaxel Versus Paclitaxel as Adjuvant Chemotherapy in Axillary Lymph Node (+) Breast Cancer

Study Overview
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Brief Summary
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Anthracycline-containing regimens are recommended as adjuvant treatment for women with node positive breast cancer. In at least three large randomized clinical trials the addition or sequential administration of a taxane (paclitaxel or docetaxel) to an antracycline-based regimen resulted in superior clinical outcome for women with node positive 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

Detailed Description
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This trial will compare the dose dense, G-CSF supported sequential administration of 4 cycles of 5-Fluoruracil (F) plus Epirubicin (E 75mg/m2) plus Cyclofosfamide (C) followed by 4 cycles of docetaxel versus 4 cycles of paclitaxel as adjuvant chemotherapy in women with axillary lymph node positive breast cancer

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 Paclitaxel as Adjuvant Chemotherapy in Women With Axillary Lymph Node Positive Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Paclitaxel
* 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
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>FEC -> TXT | Drug: Docetaxel<br>* Docetaxel 75 mg/m2 as an IV infusion over 1h every two weeks for 4 cycles<br>* Other names: Taxotere;Drug: Epirubicin<br>* Epirubicin 75 mg/m2 IV push on day 1 every 2 weeks for 4 cycles<br>* Other names: Farmorubicin;Drug: Cyclophosphamide<br>* Cyclophosphamide 700 mg/m2 IV push on day 1 every 4 weeks<br>* Other names: Endoxan;Drug: 5-fluoruracil<br>* 5-fluoruracil 700 mg/m2 IV push on day 1 every 4 weeks<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: 2<br>FEC -> TXL | Drug: Paclitaxel<br>* Paclitaxel 175 mg/m2 as an IV infusion over 3hrs every two weeks for 4 cycles<br>* Other names: Taxol;Drug: Epirubicin<br>* Epirubicin 75 mg/m2 IV push on day 1 every 2 weeks for 4 cycles<br>* Other names: Farmorubicin;Drug: Cyclophosphamide<br>* Cyclophosphamide 700 mg/m2 IV push on day 1 every 4 weeks<br>* Other names: Endoxan;Drug: 5-fluoruracil<br>* 5-fluoruracil 700 mg/m2 IV push on day 1 every 4 weeks<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;|

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 | 
| Τoxicity profile |  | Toxicity assessment on each chemotherapy cycle | 
| Quality of life between the two treatment arms |  | Assessment every two cycles | 

 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, Adjuvant chemotherapy, Dose dense, Docetaxel, Paclitaxel, FEC