6xFU/Epirubicin/Cyclophosphamide (FEC) Compared to 3xFEC-3xDocetaxel in High-risk Node-negative Breast Cancer Patients

Study Overview
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Brief Summary
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In low-risk node-negative breast cancer patients adjuvant chemotherapy should be spared. The identification of this subgroup can be based either on clinical and pathological or on tumour-biological criteria. Due to their high prognostic impact, the tumour-biological invasion markers uPA/PAI-1 (urokinase-type plasminogen activator and its inhibitor PAI-1) are potential candidates to effectively assess the risk of relapse in node-negative breast cancer. This study is aimed to compare the risk assessment by the traditional clinico-pathological factors and by tumour-biological factors. The second study question refers to the comparison between an adjuvant combination treatment with FE100C*6 and a sequential treatment with FE100C*3 and Docetaxel*3.

Detailed Description
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To compare FEC*6 with FEC*3 followed by DOC*3 with regard to: the primary endpoint of the study: Disease-Free Survival (DFS) the secondary endpoints: Overall Survival (OS), compliance, and toxicity of chemotherapy in each patient group To compare patients with low risk according to clinico-pathological versus those according to biological risk criteria with regard to: the proportion of low risk versus high risk patients DFS OS (secondary endpoint)

Official Title
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Randomized Multicenter Study Comparing 6xFEC With 3xFEC-3xDoc in High-risk Node-negative Patients With Operable Breast Cancer: Comparison of Efficacy and Evaluation of Clinico-pathological and Biochemical Markers as Risk Selection Criteria

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: 5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological proven primary breast cancer Tumour size >0.5 cm and <5 cm (pT1b-pT2, pN0, M0) Axillary lymph nodes tumour free (node-negative disease) Adequate surgical procedure: R0-resection and axillary dissection with more than 10 lymph nodes examined or adequate sentinel procedure in a qualified centre Frozen tumour tissue available (for analysis of biological markers and microarrays, centres with biological risk assessment only). The material has to be stored in liquid nitrogen immediately after excision. Paraffin blocks or (at least) pathology slides of primary tumour (stained and unstained) and axillary nodes (stained) available for central review. HER-2/neu determination by immunohistochemistry. Patients will be stratified to be HER-2/neu-negative or HER-2/neu-positive (HER-2/neu Score 3+, or HER-2/neu Score 2+ and FISH positive). No distant metastasis Age >18 years, <70 years Performance status ECOG <2 (WHO Performance Status 0-1) Adequate cardiac function (echocardiographically measured left ventricular ejection fraction (LVEF) or shortening fraction (SF) within the normal limits, i.e. ≥55%) Adequate bone function (neutrophil count >1.5 x109 /l and platelet count >100 x109 /l) Adequate renal function (serum creatinine <120 µmol/l or 1.35 mg/dl) and hepatic function (serum bilirubin <1 x UNL, ASAT or ALAT (SGOT or SGPT) <2,5 x UNL) Before patient registration/randomization, written informed consent must be obtained according to ICH/EU GCP, and national/local regulations Exclusion Criteria: Chemotherapy contraindicated Inflammatory breast cancer, tumour infiltrated axillary lymph nodes including the sentinel node. Other concomitant pathology compromising survival (at entry), or preventing the administration of chemotherapy with either FEC or Docetaxel Other serious illness or medical condition that may interfere with the understanding and giving of informed consent and the conduct of the study Estimated life-expectancy <10 years (irrespective of breast cancer diagnosis) Patient not accessible for treatment and follow up Endocrine treatment not according to the latest standard recommendations of the AGO Kommission Mamma Pregnancy, lactation (sufficient non-hormonal contraception in fertile women required) Surgery more than six weeks ago at the start of chemotherapy Pre-existing polyneuropathy Previous or concomitant other malignancy (including contralateral breast cancer) except adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix Prior chemotherapy or radiotherapy or endocrine therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Arm A Taxane-containing<br>3 courses FEC q3weeks followed by 3 courses Docetaxel q3weeks | Drug: 5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel<br>* Arm A 5-FU 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2 q3weeks followed by Docetaxel 100 mg/m² q3weeks Arm B 5-FU 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2 q6weeks<br>|
| Active Comparator: Arm B standard anthracyclin<br>6 courses of FEC q3weeks | Drug: 5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel<br>* Arm A 5-FU 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2 q3weeks followed by Docetaxel 100 mg/m² q3weeks Arm B 5-FU 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2 q6weeks<br>|
| No Intervention: Observation<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-Free Survival |  | after 10 years follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | after 10 years follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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high risk breast cancer, low risk breast cancer, uPA, urokinase-type plasminogen activator, PAI, plasminogen activator inhibitor-type