6xFU/Epirubicin/Cyclophosphamide (FEC) Compared to 3xFEC-3xDocetaxel in High-risk Node-negative Breast Cancer Patients (NNBC3-Europe)
Primary Purpose
Breast Cancer
Status
Unknown status
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring high risk breast cancer, low risk breast cancer, uPA, urokinase-type plasminogen activator, PAI, plasminogen activator inhibitor-type
Eligibility 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
Sites / Locations
- GBG Forschungs GmbH
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
No Intervention
Arm Label
Arm A Taxane-containing
Arm B standard anthracyclin
Observation
Arm Description
3 courses FEC q3weeks followed by 3 courses Docetaxel q3weeks
6 courses of FEC q3weeks
Outcomes
Primary Outcome Measures
Disease-Free Survival
Secondary Outcome Measures
Overall Survival
Full Information
NCT ID
NCT01222052
First Posted
October 15, 2010
Last Updated
June 23, 2017
Sponsor
Martin-Luther-Universität Halle-Wittenberg
Collaborators
German Breast Group
1. Study Identification
Unique Protocol Identification Number
NCT01222052
Brief Title
6xFU/Epirubicin/Cyclophosphamide (FEC) Compared to 3xFEC-3xDocetaxel in High-risk Node-negative Breast Cancer Patients
Acronym
NNBC3-Europe
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Unknown status
Study Start Date
January 2002 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
February 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Martin-Luther-Universität Halle-Wittenberg
Collaborators
German Breast Group
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
high risk breast cancer, low risk breast cancer, uPA, urokinase-type plasminogen activator, PAI, plasminogen activator inhibitor-type
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
4150 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A Taxane-containing
Arm Type
Experimental
Arm Description
3 courses FEC q3weeks followed by 3 courses Docetaxel q3weeks
Arm Title
Arm B standard anthracyclin
Arm Type
Active Comparator
Arm Description
6 courses of FEC q3weeks
Arm Title
Observation
Arm Type
No Intervention
Intervention Type
Drug
Intervention Name(s)
5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel
Intervention Description
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
Primary Outcome Measure Information:
Title
Disease-Free Survival
Time Frame
after 10 years follow up
Secondary Outcome Measure Information:
Title
Overall Survival
Time Frame
after 10 years follow up
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christoph Thomssen, MD
Organizational Affiliation
Dpt. Gynecology University Halle Germany
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nadia Harbeck, MD
Organizational Affiliation
Breast Center University Cologne
Official's Role
Principal Investigator
Facility Information:
Facility Name
GBG Forschungs GmbH
City
Neu-Isenburg
ZIP/Postal Code
63263
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
21496284
Citation
Kantelhardt EJ, Vetter M, Schmidt M, Veyret C, Augustin D, Hanf V, Meisner C, Paepke D, Schmitt M, Sweep F, von Minckwitz G, Martin PM, Jaenicke F, Thomssen C, Harbeck N. Prospective evaluation of prognostic factors uPA/PAI-1 in node-negative breast cancer: phase III NNBC3-Europe trial (AGO, GBG, EORTC-PBG) comparing 6xFEC versus 3xFEC/3xDocetaxel. BMC Cancer. 2011 Apr 16;11:140. doi: 10.1186/1471-2407-11-140.
Results Reference
derived
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6xFU/Epirubicin/Cyclophosphamide (FEC) Compared to 3xFEC-3xDocetaxel in High-risk Node-negative Breast Cancer Patients
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