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Biomarker (p53 Gene) Analysis and Combination Chemotherapy Followed by Radiation Therapy and Surgery in Treating Women With Large Operable or Locally Advanced or Inflammatory Breast Cancer
The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2010 by National Cancer Institute (NCI).   Recruitment status was  Active, not recruiting

First Received on June 6, 2001.   Last Updated on June 23, 2011   History of Changes
Sponsor: European Organization for Research and Treatment of Cancer - EORTC
Collaborators: Swedish Breast Cancer Group
Swiss Group for Clinical Cancer Research
Anglo Celtic Cooperative Oncology Group
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00017095
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Biological: filgrastim
Drug: cyclophosphamide
Drug: docetaxel
Drug: epirubicin hydrochloride
Drug: fluorouracil
Genetic: microarray analysis
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Procedure: biopsy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Radiation: radiation therapy
Phase III

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: First Prospective Intergroup Translational Research Trial Assessing the Potential Predictive Value of p53 Using a Functional Assay in Yeast in Patients With Locally Advanced/Inflammatory or Large Operable Breast Cancer Prospectively Randomised to a Taxane Versus a Non Taxane Regimen

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Distant metastasis-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Clinical and pathological responses [ Designated as safety issue: No ]
  • Clinical response according to RECIST criteria without pathologic response [ Designated as safety issue: No ]
  • Toxicity according to CTC v2.0 [ Designated as safety issue: Yes ]
  • Agreement between p53 assessment by IHC method and functional test in yeast by analyzing the correlation between p52 and tumor status after 3 and 6 cycles of chemotherapy [ Designated as safety issue: No ]
  • Tumor assessment using cDNA microarray technology [ Designated as safety issue: No ]

Estimated Enrollment: 1850
Study Start Date: March 2001
  Show Detailed Description

  Eligibility

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

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00017095

  Show 39 Study Locations
Sponsors and Collaborators
European Organization for Research and Treatment of Cancer - EORTC
Swedish Breast Cancer Group
Swiss Group for Clinical Cancer Research
Anglo Celtic Cooperative Oncology Group
Investigators
Investigator: Herve Bonnefoi, MD Hopital Cantonal Universitaire de Geneve
Study Chair: Jonas Bergh, MD, PhD Karolinska University Hospital, Solna
Study Chair: Barbara Muster Swiss Group for Clinical Cancer Research
Study Chair: Kirsten Murray Scottish Cancer Therapy Network
  More Information

Additional Information:
Publications:
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, André S, Litière S, Lago LD, Becette V, Cameron DA, Bergh J, Iggo R; on behalf of the 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 May 11; [Epub ahead of print]
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.
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 Jul 26; [Epub ahead of print] No abstract available.
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.
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, André 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 Nov 13; [Epub ahead of print]
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.
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.
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.
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, André 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. No abstract available.
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. Epub 2011 Mar 21.

ClinicalTrials.gov Identifier: NCT00017095     History of Changes
Other Study ID Numbers: CDR0000068649, EORTC-10994, ACCOG-EORTC-10994, SAKK-EORTC-10994, SBGC-EORTC-10994, BIG-1-00
Study First Received: June 6, 2001
Last Updated: June 23, 2011
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
inflammatory breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Inflammatory Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Fluorouracil
Docetaxel
Epirubicin
Lenograstim
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
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on February 12, 2012