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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
German Breast Group
Information provided by (Responsible Party):
Christoph Thomssen, Martin-Luther-Universität Halle-Wittenberg
ClinicalTrials.gov Identifier:
NCT01222052
First received: October 15, 2010
Last updated: September 3, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: 5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Martin-Luther-Universität Halle-Wittenberg:

Primary Outcome Measures:
  • Disease-Free Survival [ Time Frame: after 10 years follow up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall Survival [ Time Frame: after 10 years follow up ] [ Designated as safety issue: No ]

Enrollment: 4150
Study Start Date: January 2002
Estimated Study Completion Date: February 2019
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

No Intervention: Observation

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)
  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01222052

Locations
Germany
GBG Forschungs GmbH
Neu-Isenburg, Germany, 63263
Sponsors and Collaborators
Martin-Luther-Universität Halle-Wittenberg
German Breast Group
Investigators
Principal Investigator: Christoph Thomssen, MD Dpt. Gynecology University Halle Germany
Principal Investigator: Nadia Harbeck, MD Breast Center University Cologne
  More Information

No publications provided by Martin-Luther-Universität Halle-Wittenberg

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Christoph Thomssen, Prof. Dr. Christoph Thomssen, Martin-Luther-Universität Halle-Wittenberg
ClinicalTrials.gov Identifier: NCT01222052     History of Changes
Other Study ID Numbers: GBG 42
Study First Received: October 15, 2010
Last Updated: September 3, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Martin-Luther-Universität Halle-Wittenberg:
high risk breast cancer
low risk breast cancer
uPA
urokinase-type plasminogen activator
PAI
plasminogen activator inhibitor-type

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Fluorouracil
Docetaxel
Epirubicin
Plasminogen Inactivators
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014