6xFU/Epirubicin/Cyclophosphamide (FEC) Compared to 3xFEC-3xDocetaxel in High-risk Node-negative Breast Cancer Patients (NNBC3-Europe)

June 23, 2017 updated by: Christoph Thomssen, Martin-Luther-Universität Halle-Wittenberg

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

  1. 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

  2. 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)

Study Type

Interventional

Enrollment (Actual)

4150

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Neu-Isenburg, Germany, 63263
        • GBG Forschungs GmbH

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Observation
Experimental: Arm A Taxane-containing
3 courses FEC q3weeks followed by 3 courses Docetaxel q3weeks
Drug: 5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel

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
Active Comparator: Arm B standard anthracyclin
6 courses of FEC q3weeks
Drug: 5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall Survival
Time Frame: after 10 years follow up
after 10 years follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Martin-Luther-Universität Halle-Wittenberg

Collaborators

German Breast Group

Investigators

  • Principal Investigator: Christoph Thomssen, MD, Dpt. Gynecology University Halle Germany
  • Principal Investigator: Nadia Harbeck, MD, Breast Center University Cologne

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2002

Primary Completion (Actual)

February 1, 2009

Study Completion (Anticipated)

February 1, 2019

Study Registration Dates

First Submitted

October 15, 2010

First Submitted That Met QC Criteria

October 15, 2010

First Posted (Estimate)

October 18, 2010

Study Record Updates

Last Update Posted (Actual)

June 26, 2017

Last Update Submitted That Met QC Criteria

June 23, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GBG 42

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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