Six vs 12 Months of Trastuzumab With Docetaxel Following FEC as Adjuvant Treatment in N+ Breast Cancer

Study Overview
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Brief Summary
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This trial will compare 6 versus 12 months of trastuzumab in combination with dose dense docetaxel following FE75C as adjuvant chemotherapy in women with axillary lymph node positive breast cancer overexpressing HER2

Detailed Description
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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. Trastuzumab (anti-HER2 monoclonal antibody) in combination with paclitaxel was superior to paclitaxel alone in women with metastatic breast cancer overexpressing HER2

Official Title
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A Multicenter Randomized Phase III Study Comparing 6 Versus 12 Months of Trastuzumab in Combination With Dose Dense Docetaxel Following FE75C as Adjuvant Treatment of Women With Axillary Lymph Node Positive Breast Cancer Over-expressing HER2

Conditions
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Breast Cancer

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


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 HER2/c-neu over expression should be documented by either immunohistochemistry (score 3+) or FISH/CISH positivity. A score of 2+ by immunohistochemistry is acceptable only if FISH/CISH positive 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 (N0 with HER2/c-neu over expression are also eligible) 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%). Normal electrocardiogram and absence of significant heart disease 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+H 12m | Drug: Docetaxel<br>* Docetaxel 75 mg/m2 as an IV infusion over 1h every two weeks for 4 cycles<br>* Other names: Taxotere;Drug: Trastuzumab<br>* Trastuzumab 6 mg/Kg IV over 30 min every two weeks for 4 cycles. Subsequently,trastuzumab 6 mg/Kg IV over 30 min for 12 months<br>* Other names: Herceptin;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 -> TXT+H 6m | 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;Drug: Trastuzumab<br>* Trastuzumab 6mg/Kg IV over 30 min every 2 weeks for 4 cycles. Subsequently, trastuzumab 6mg/Kg IV over 30 min for 6 months<br>* Other names: Herceptin;|

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 |  | 5 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, HER2 overexpression, Adjuvant chemotherapy, Dose dense, Docetaxel, Trastuzumab, FEC