NCT00017095

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Currently patients with breast cancer are treated with one of several very similar combinations of drugs. Analysis of biomarkers in tumor tissue may help doctors predict how well patients with breast cancer will respond to treatment and help doctors choose the best drug regimen to treat each patient. PURPOSE: This randomized phase III trial is studying giving different regimens of chemotherapy and comparing how well they work in treating women with large operable or locally advanced or inflammatory breast cancer. This study is also looking at whether analyzing a specific biomarker (p53) in tumor tissue may help doctors predict how well patients will respond to treatment and help doctors choose the best drug to treat each patient.

Trial Health

90
On Track

Trial Health Score

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

Enrollment
1,856

participants targeted

Target at P75+ for phase_3 breast-cancer

Geographic Reach
9 countries

39 active sites

Status
completed

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

March 1, 2001

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

June 6, 2001

Completed
1.6 years until next milestone

First Posted

Study publicly available on registry

January 27, 2003

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2006

Completed
Last Updated

October 24, 2013

Status Verified

October 1, 2013

Enrollment Period

5.7 years

First QC Date

June 6, 2001

Last Update Submit

October 23, 2013

Conditions

Breast Cancer

Keywords

stage II breast cancerstage IIIA breast cancerstage IIIB breast cancerstage IIIC breast cancerinflammatory breast cancer

Outcome Measures

Primary Outcomes (1)

  • Progression-free survival

    from randomization till first evidence of progression

Secondary Outcomes (7)

  • Distant metastasis-free survival

    randomization till first evidence recurrence

  • Overall survival

    randomization till death

  • Clinical and pathological responses

    after 3rd and 6d cycle of chemotherapy

  • Clinical response according to RECIST criteria without pathologic response

    after 3rd and 6d cycle of chemotherapy

  • Toxicity according to CTC v2.0

    from randomization

  • +2 more secondary outcomes

Study Arms (2)

non taxane based chemotherapy

ACTIVE COMPARATOR

either FEC 100 or Canadian CEF or Tailored FEC for 6 cycles

Biological: filgrastimDrug: cyclophosphamideDrug: epirubicin hydrochlorideDrug: fluorouracilGenetic: microarray analysisOther: immunohistochemistry staining methodOther: laboratory biomarker analysisProcedure: biopsyProcedure: conventional surgeryProcedure: neoadjuvant therapyRadiation: radiation therapy

taxane based chemotherapy

EXPERIMENTAL

Docetaxel for 3 cycles followed by Epirubicin/Docetaxel for 3 cycles

Drug: docetaxelDrug: epirubicin hydrochlorideGenetic: microarray analysisOther: immunohistochemistry staining methodOther: laboratory biomarker analysisProcedure: biopsyProcedure: conventional surgeryProcedure: neoadjuvant therapyRadiation: radiation therapy

Interventions

filgrastimBIOLOGICAL
non taxane based chemotherapy
cyclophosphamideDRUG
non taxane based chemotherapy
docetaxelDRUG
taxane based chemotherapy
epirubicin hydrochlorideDRUG
non taxane based chemotherapytaxane based chemotherapy
fluorouracilDRUG
non taxane based chemotherapy
microarray analysisGENETIC
non taxane based chemotherapytaxane based chemotherapy
immunohistochemistry staining methodOTHER
non taxane based chemotherapytaxane based chemotherapy
laboratory biomarker analysisOTHER
non taxane based chemotherapytaxane based chemotherapy
biopsyPROCEDURE
non taxane based chemotherapytaxane based chemotherapy
conventional surgeryPROCEDURE
non taxane based chemotherapytaxane based chemotherapy
neoadjuvant therapyPROCEDURE
non taxane based chemotherapytaxane based chemotherapy
radiation therapyRADIATION
non taxane based chemotherapytaxane based chemotherapy

Eligibility Criteria

AgeUp to 70 Years
Sexfemale
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
DISEASE CHARACTERISTICS: * Histologically confirmed breast cancer * Locally advanced or inflammatory disease * T4a-d, any N, M0 OR * Any T, N2 or N3, M0 * Large operable T2 or T3 tumors * No bilateral breast cancer * Frozen tumor sample available * 1 incisional biopsy OR * 2 trucut biopsies from a 14G needle * Hormone receptor status: * Not specified PATIENT CHARACTERISTICS: Age: * 70 and under Sex: * Female Menopausal status: * Not specified Performance status: * WHO 0-1 Life expectancy: * Not specified Hematopoietic: * Neutrophil count greater than 1,500/mm\^3 * Platelet count greater than 100,000/mm\^3 Hepatic: * Bilirubin less than 1.2 mg/dL * SGOT less than 60 IU/L Renal: * Creatinine less than 1.35 mg/dL Cardiovascular: * LVEF normal by echocardiography or MUGA Other: * No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * No serious uncontrolled medical condition * No uncontrolled psychiatric or addictive disorders * Not pregnant or nursing * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * No prior chemotherapy Endocrine therapy: * Not specified Radiotherapy: * No prior radiotherapy Surgery: * See Disease Characteristics

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (39)

Institut Jules Bordet

Brussels, 1000, Belgium

Location

CHU Liege - Domaine Universitaire du Sart Tilman

Liège, B-4000, Belgium

Location

Algemeen Ziekenhuis Sint-Augustinus

Wilrijk, 2610, Belgium

Location

Centre Paul Papin

Angers, 49036, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

Dijon, 21079, France

Location

Centre Hospitalier Departemental

La Roche-sur-Yon, F-85025, France

Location

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

Montpellier, 34298, France

Location

Centre Regional Rene Gauducheau

Nantes-Saint Herblain, 44805, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Centre Rene Huguenin

Saint-Cloud, 92211, France

Location

Centre Paul Strauss

Strasbourg, 67085, France

Location

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, 54511, France

Location

Onze Lieve Vrouwe Gasthuis

Amsterdam, 1091 HA, Netherlands

Location

Leiden University Medical Center

Leiden, 2300 CA, Netherlands

Location

Daniel Den Hoed Cancer Center at Erasmus Medical Center

Rotterdam, 3008 AE, Netherlands

Location

Medical University of Gdansk

Gdansk, 80-211, Poland

Location

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology

Warsaw, 02-781, Poland

Location

Hospitais da Universidade de Coimbra (HUC)

Coimbra, 3049, Portugal

Location

Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, S.A.

Lisbon, 1099-023 Codex, Portugal

Location

Institute of Oncology - Ljubljana

Ljubljana, Sl-1000, Slovenia

Location

Sahlgrenska University Hospital at Gothenburg University

Gothenburg (Goteborg), S-413 45, Sweden

Location

Lund University Hospital

Lund, S-22185, Sweden

Location

Malmo University Hospital

Malmo, S-20502, Sweden

Location

Sahlgrenska University Hospital - Molndal at Gothenburg University

Mölndal, S-43180, Sweden

Location

Orebro University Hospital

Örebro, 70185, Sweden

Location

Karolinska University Hospital - Huddinge

Stockholm, S-171 76, Sweden

Location

Uppsala University Hospital

Uppsala, S-75185, Sweden

Location

Kantonspital Aarau

Aarau, 5001, Switzerland

Location

Swiss Institute for Applied Cancer Research

Bern, CH-3008, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Hopital Cantonal Universitaire de Geneve

Geneva, CH-1211, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, CH-8091, Switzerland

Location

Northern Centre for Cancer Treatment at Newcastle General Hospital

Newcastle upon Tyne, England, NE4 6BE, United Kingdom

Location

Royal South Hants Hospital

Southampton, England, SO14 0YG, United Kingdom

Location

Ninewells Hospital and Medical School

Dundee, Scotland, DD1 9SY, United Kingdom

Location

Edinburgh Cancer Centre at Western General Hospital

Edinburgh, Scotland, EH4 2XU, United Kingdom

Location

Scottish Cancer Therapy Network

Edinburgh, Scotland, EH5 3SQ, United Kingdom

Location

Related Publications (12)

  • Bonnefoi H, Potti A, Delorenzi M, Mauriac L, Campone M, Tubiana-Hulin M, Petit T, Rouanet P, Jassem J, Blot E, Becette V, Farmer P, Andre S, Acharya CR, Mukherjee S, Cameron D, Bergh J, Nevins JR, Iggo RD. Retraction--Validation of gene signatures that predict the response of breast cancer to neoadjuvant chemotherapy: a substudy of the EORTC 10994/BIG 00-01 clinical trial. Lancet Oncol. 2011 Feb;12(2):116. doi: 10.1016/S1470-2045(11)70011-0. No abstract available.

    PMID: 21277543BACKGROUND

  • Desmedt C, Di Leo A, de Azambuja E, Larsimont D, Haibe-Kains B, Selleslags J, Delaloge S, Duhem C, Kains JP, Carly B, Maerevoet M, Vindevoghel A, Rouas G, Lallemand F, Durbecq V, Cardoso F, Salgado R, Rovere R, Bontempi G, Michiels S, Buyse M, Nogaret JM, Qi Y, Symmans F, Pusztai L, D'Hondt V, Piccart-Gebhart M, Sotiriou C. Multifactorial approach to predicting resistance to anthracyclines. J Clin Oncol. 2011 Apr 20;29(12):1578-86. doi: 10.1200/JCO.2010.31.2231. Epub 2011 Mar 21.

    PMID: 21422418BACKGROUND

  • Bonnefoi H, Piccart M, Bogaerts J, Mauriac L, Fumoleau P, Brain E, Petit T, Rouanet P, Jassem J, Blot E, Zaman K, Cufer T, Lortholary A, Lidbrink E, Andre S, Litiere S, Lago LD, Becette V, Cameron DA, Bergh J, Iggo R; EORTC 10994/BIG 1-00 Study Investigators. TP53 status for prediction of sensitivity to taxane versus non-taxane neoadjuvant chemotherapy in breast cancer (EORTC 10994/BIG 1-00): a randomised phase 3 trial. Lancet Oncol. 2011 Jun;12(6):527-39. doi: 10.1016/S1470-2045(11)70094-8. Epub 2011 May 11.

    PMID: 21570352RESULT

  • Bonnefoi HR, Bogaerts J, Piccart M, et al.: Phase III trial (EORTC 10994/BIG 00-01) assessing the value of p53 using a functional assay to predict sensitivity to a taxane versus nontaxane primary chemotherapy in breast cancer: final analysis. [Abstract] J Clin Oncol 28 (Suppl 18): A-LBA503, 2010.

    RESULT

  • Collingridge D. Expression of concern--validation of gene signatures that predict the response of breast cancer to neoadjuvant chemotherapy: a substudy of the EORTC 10994/BIG 00-01 clinical trial. Lancet Oncol. 2010 Sep;11(9):813-4. doi: 10.1016/S1470-2045(10)70185-6. Epub 2010 Jul 26. No abstract available.

    PMID: 20667781RESULT

  • Bonnefoi H, Zimmer AS, Piccart M, et al.: P53 functional assay in yeast: evaluation in 1856 patients in a large prospective clinical trial: EORTC 10994/BIG 00-01. [Abstract] 31st Annual San Antonio Breast Cancer Symposium, December 10-14, 2008, San Antonio, Texas. A-1067, 2008.

    RESULT

  • Bonnefoi H, Potti A, Delorenzi M, Mauriac L, Campone M, Tubiana-Hulin M, Petit T, Rouanet P, Jassem J, Blot E, Becette V, Farmer P, Andre S, Acharya CR, Mukherjee S, Cameron D, Bergh J, Nevins JR, Iggo RD. Validation of gene signatures that predict the response of breast cancer to neoadjuvant chemotherapy: a substudy of the EORTC 10994/BIG 00-01 clinical trial. Lancet Oncol. 2007 Dec;8(12):1071-1078. doi: 10.1016/S1470-2045(07)70345-5. Epub 2007 Nov 19.

    PMID: 18024211RESULT

  • Karina M, Bogaerts J, Piccart M, et al.: Preliminary safety data of the EORTC 10994/BIG 00-01 neoadjuvant trial comparing 3 cycles of docetaxel followed by 3 cycles of epirubicin-docetaxel versus 6 cycles of FEC 100 in patients with locally advanced/inflammatory or large operable breast cancer. [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-3067, S146-7, 2006.

    RESULT

  • Bonnefoi H, Farmer P, Delorenzi M, et al.: Is there a regimen-specific gene signature predicting for pathological complete response after neoadjuvant chemotherapy in hormone-negative breast cancer patients? A microarray substudy of 101 patients included in EORTC 10994/BIG 00-01 trial. [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-1040, 2005.

    RESULT

  • Farmer P, Iggo R, Becette V, et al.: High quality gene expression microarray data from a multicentre prospective trial: results of the first microarray analysis in the EORTC 10994/ BIG 00-01 study. [Abstract] Eur J Cancer 2 (Suppl 3): A-155, 99, 2004.

    RESULT

  • Chatzipli A, Bonnefoi H, MacGrogan G, Sentis J, Cameron D, Poncet C; EORTC 10994/BIG 1-00 Consortium; Iggo R. Patterns of genomic change in residual disease after neoadjuvant chemotherapy for estrogen receptor-positive and HER2-negative breast cancer. Br J Cancer. 2021 Nov;125(10):1356-1364. doi: 10.1038/s41416-021-01526-3. Epub 2021 Sep 3.

    PMID: 34480095DERIVED

  • Bonnefoi H, Litiere S, Piccart M, MacGrogan G, Fumoleau P, Brain E, Petit T, Rouanet P, Jassem J, Moldovan C, Bodmer A, Zaman K, Cufer T, Campone M, Luporsi E, Malmstrom P, Werutsky G, Bogaerts J, Bergh J, Cameron DA; EORTC 10994/BIG 1-00 Study investigators. Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial. Ann Oncol. 2014 Jun;25(6):1128-36. doi: 10.1093/annonc/mdu118. Epub 2014 Mar 11.

    PMID: 24618153DERIVED

MeSH Terms

Conditions

Breast NeoplasmsInflammatory Breast Neoplasms

Interventions

FilgrastimCyclophosphamideDocetaxelEpirubicinFluorouracilMicroarray AnalysisImmunohistochemistryBiopsyNeoadjuvant TherapyRadiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating FactorColony-Stimulating FactorsGlycoproteinsGlycoconjugatesCarbohydratesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological FactorsPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicDiterpenesTerpenesDoxorubicinDaunorubicinAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticPolycyclic CompoundsAminoglycosidesGlycosidesUracilPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsMicrochip Analytical ProceduresInvestigative TechniquesHistocytochemistryCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisHistological TechniquesImmunologic TechniquesCytodiagnosisSpecimen HandlingDiagnostic Techniques, SurgicalSurgical Procedures, OperativeCombined Modality TherapyTherapeutics

Study Officials

  • Herve Bonnefoi

    Institut Bergonie, Bordeaux

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 6, 2001

First Posted

January 27, 2003

Study Start

March 1, 2001

Primary Completion

November 1, 2006

Last Updated

October 24, 2013

Record last verified: 2013-10

Locations

NL(3)SL(1)SE(7)BE(3)PL(2)CH(6)FR(10)GB(5)PT(2)