NCT01222052

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
4,150

participants targeted

Target at P75+ for phase_3 breast-cancer

Timeline
Completed

Started Jan 2002

Longer than P75 for phase_3 breast-cancer

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2002

Completed
7.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2009

Completed
1.7 years until next milestone

First Submitted

Initial submission to the registry

October 15, 2010

Completed
3 days until next milestone

First Posted

Study publicly available on registry

October 18, 2010

Completed
8.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2019

Completed
Last Updated

June 26, 2017

Status Verified

June 1, 2017

Enrollment Period

7.1 years

First QC Date

October 15, 2010

Last Update Submit

June 23, 2017

Conditions

Breast Cancer

Keywords

high risk breast cancerlow risk breast canceruPAurokinase-type plasminogen activatorPAIplasminogen activator inhibitor-type

Outcome Measures

Primary Outcomes (1)

  • Disease-Free Survival

    after 10 years follow up

Secondary Outcomes (1)

  • Overall Survival

    after 10 years follow up

Study Arms (3)

Arm A Taxane-containing

EXPERIMENTAL

3 courses FEC q3weeks followed by 3 courses Docetaxel q3weeks

Drug: 5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel

Arm B standard anthracyclin

ACTIVE COMPARATOR

6 courses of FEC q3weeks

Drug: 5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel

Observation

NO INTERVENTION

Interventions

5-Fluorouracil, Epirubicin, Cyclophosphamide, DocetaxelDRUG

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

Arm A Taxane-containingArm B standard anthracyclin

Eligibility Criteria

Age18 Years - 70 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

GBG Forschungs GmbH

Neu-Isenburg, 63263, Germany

Location

Related Publications (1)

  • 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.

    PMID: 21496284DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

FluorouracilEpirubicinCyclophosphamideDocetaxel

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

UracilPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsDoxorubicinDaunorubicinAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydratesPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedPhosphoramidesOrganophosphorus CompoundsTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicDiterpenesTerpenes

Study Officials

  • Christoph Thomssen, MD

    Dpt. Gynecology University Halle Germany

    PRINCIPAL INVESTIGATOR

  • Nadia Harbeck, MD

    Breast Center University Cologne

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof. Dr. Christoph Thomssen

Study Record Dates

First Submitted

October 15, 2010

First Posted

October 18, 2010

Study Start

January 1, 2002

Primary Completion

February 1, 2009

Study Completion

February 1, 2019

Last Updated

June 26, 2017

Record last verified: 2017-06

Locations

DE(1)