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

This study has been completed.
Sponsor:
Collaborators:
Swedish Breast Cancer Group
Swiss Group for Clinical Cancer Research
Anglo Celtic Cooperative Oncology Group
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00017095
First received: June 6, 2001
Last updated: October 23, 2013
Last verified: October 2013
  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 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
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 European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: from randomization till first evidence of progression ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Distant metastasis-free survival [ Time Frame: randomization till first evidence recurrence ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: randomization till death ] [ Designated as safety issue: No ]
  • Clinical and pathological responses [ Time Frame: after 3rd and 6d cycle of chemotherapy ] [ Designated as safety issue: No ]
  • Clinical response according to RECIST criteria without pathologic response [ Time Frame: after 3rd and 6d cycle of chemotherapy ] [ Designated as safety issue: No ]
  • Toxicity according to CTC v2.0 [ Time Frame: from randomization ] [ 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 [ Time Frame: after 3 and 6 cycles of chemotherapy ] [ Designated as safety issue: No ]
  • Tumor assessment using cDNA microarray technology [ Time Frame: end of treatment ] [ Designated as safety issue: No ]

Enrollment: 1856
Study Start Date: March 2001
Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: non taxane based chemotherapy
either FEC 100 or Canadian CEF or Tailored FEC for 6 cycles
Biological: filgrastim Drug: cyclophosphamide 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
Experimental: taxane based chemotherapy
Docetaxel for 3 cycles followed by Epirubicin/Docetaxel for 3 cycles
Drug: docetaxel Drug: epirubicin hydrochloride Genetic: microarray analysis Other: immunohistochemistry staining method Other: laboratory biomarker analysis Procedure: biopsy Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: radiation therapy

  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
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: NCT00017095

  Show 39 Study Locations
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Swedish Breast Cancer Group
Swiss Group for Clinical Cancer Research
Anglo Celtic Cooperative Oncology Group
Investigators
Study Chair: Herve Bonnefoi Institut Bergonie, Bordeaux
  More Information

Additional Information:
Publications:
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.
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.
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.

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00017095     History of Changes
Other Study ID Numbers: EORTC-10994-p53, EORTC-10994, ACCOG-EORTC-10994, SAKK-EORTC-10994, SBGC-EORTC-10994, BIG-1-00
Study First Received: June 6, 2001
Last Updated: October 23, 2013
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
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
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antimetabolites
Antimetabolites, Antineoplastic
Tubulin Modulators
Antimitotic Agents

ClinicalTrials.gov processed this record on September 14, 2014