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
- Conditions
- Breast Cancer
- Interventions
- Biological: filgrastimGenetic: microarray analysisOther: laboratory biomarker analysisOther: immunohistochemistry staining methodProcedure: biopsyProcedure: neoadjuvant therapyProcedure: conventional surgeryRadiation: radiation therapy
- Registration Number
- 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.
- Detailed Description
OBJECTIVES:
Primary
* Compare neoadjuvant fluorouracil, epirubicin, and cyclophosphamide vs docetaxel and epirubicin followed by radiotherapy and surgery in women with locally advanced, inflammatory, or large operable breast cancer.
* Assess overall differences between the two arms.
* Assess interaction between p53 status and outcomes in each arm.
* Compare the progression-free survival of patients treated with these regimens.
Secondary
* Compare the distant metastasis-free survival and survival of patients treated with these regimens.
* Compare the clinical and pathological responses to these regimens in these patients.
* Compare the toxicity of these regimens in these patients.
Translational
* Determine the p53 status in order to study the treatment effect in each of the p53 subgroups and test the interaction between treatment and p53 status.
* Assess the level of agreement between p53 assessment by IHC method and functional test in yeast.
* Evaluate the prognostic and predictive value of "high risk" p53 mutations.
* Perform a survival analysis according to gene clusters defined with the use of microarrays.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to stage of disease (large T2-3 vs locally advanced or inflammatory), p53 status (negative vs positive vs unknown), and participating center. Patients are randomized to 1 of 2 chemotherapy treatment arms.
* Arm I (non-taxane arm): Patients receive 1 of 3 chemotherapy regimens comprising fluorouracil, epirubicin, and cyclophosphamide (FEC) (according to participating institution).
* FEC 100: Patients receive fluorouracil IV over 15 minutes, epirubicin IV over 1 hour, and cyclophosphamide IV over 1 hour on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
* Canadian FEC: Patients receive oral cyclophosphamide on days 1-14 and epirubicin IV and fluorouracil IV on days 1 and 8. If oral medications are not tolerated, patients may switch to cyclophosphamide IV on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
* Tailored FEC: Patients receive fluorouracil IV over 15 minutes, epirubicin IV over 1 hour, and cyclophosphamide IV over 1-2 hours on day 1. Patients also receive filgrastim (G-CSF) subcutaneously on days 2-15 or until blood counts recover. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
* Arm II (taxane arm): Patients receive docetaxel IV over 1 hour on days 1, 22, and 43 followed by epirubicin IV over 15 minutes and docetaxel IV over 1 hour on days 64, 85, and 106 in the absence of disease progression or unacceptable toxicity.
Following chemotherapy, patients may undergo loco-regional therapy comprising radiotherapy with or without breast conservation surgery or mastectomy. Patients with estrogen- and/or progesterone-receptor-positive disease also receive tamoxifen or an aromatase inhibitor for 5 years.
Two tumor samples (incisional or tricut biopsies) are taken before chemotherapy. Samples are analyzed by IHC, a functional test in yeast, and microarray analysis.
Patients are followed every 3 months for 1 year, every 4 months for 1.5 years, and then every 6 months thereafter.
PROJECTED ACCRUAL: A total of 1,850 patients will be accrued for this study within 5.5 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 1856
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description taxane based chemotherapy microarray analysis Docetaxel for 3 cycles followed by Epirubicin/Docetaxel for 3 cycles non taxane based chemotherapy epirubicin hydrochloride either FEC 100 or Canadian CEF or Tailored FEC for 6 cycles non taxane based chemotherapy biopsy either FEC 100 or Canadian CEF or Tailored FEC for 6 cycles taxane based chemotherapy neoadjuvant therapy Docetaxel for 3 cycles followed by Epirubicin/Docetaxel for 3 cycles non taxane based chemotherapy cyclophosphamide either FEC 100 or Canadian CEF or Tailored FEC for 6 cycles non taxane based chemotherapy conventional surgery either FEC 100 or Canadian CEF or Tailored FEC for 6 cycles non taxane based chemotherapy fluorouracil either FEC 100 or Canadian CEF or Tailored FEC for 6 cycles non taxane based chemotherapy neoadjuvant therapy either FEC 100 or Canadian CEF or Tailored FEC for 6 cycles taxane based chemotherapy laboratory biomarker analysis Docetaxel for 3 cycles followed by Epirubicin/Docetaxel for 3 cycles taxane based chemotherapy conventional surgery Docetaxel for 3 cycles followed by Epirubicin/Docetaxel for 3 cycles non taxane based chemotherapy filgrastim either FEC 100 or Canadian CEF or Tailored FEC for 6 cycles non taxane based chemotherapy microarray analysis either FEC 100 or Canadian CEF or Tailored FEC for 6 cycles non taxane based chemotherapy laboratory biomarker analysis either FEC 100 or Canadian CEF or Tailored FEC for 6 cycles non taxane based chemotherapy radiation therapy either FEC 100 or Canadian CEF or Tailored FEC for 6 cycles non taxane based chemotherapy immunohistochemistry staining method either FEC 100 or Canadian CEF or Tailored FEC for 6 cycles taxane based chemotherapy epirubicin hydrochloride Docetaxel for 3 cycles followed by Epirubicin/Docetaxel for 3 cycles taxane based chemotherapy immunohistochemistry staining method Docetaxel for 3 cycles followed by Epirubicin/Docetaxel for 3 cycles taxane based chemotherapy biopsy Docetaxel for 3 cycles followed by Epirubicin/Docetaxel for 3 cycles taxane based chemotherapy radiation therapy Docetaxel for 3 cycles followed by Epirubicin/Docetaxel for 3 cycles taxane based chemotherapy docetaxel Docetaxel for 3 cycles followed by Epirubicin/Docetaxel for 3 cycles
- Primary Outcome Measures
Name Time Method Progression-free survival from randomization till first evidence of progression
- Secondary Outcome Measures
Name Time Method Clinical response according to RECIST criteria without pathologic response after 3rd and 6d cycle of chemotherapy Toxicity according to CTC v2.0 from randomization 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 after 3 and 6 cycles of chemotherapy Tumor assessment using cDNA microarray technology end of treatment Distant metastasis-free survival randomization till first evidence recurrence Clinical and pathological responses after 3rd and 6d cycle of chemotherapy Overall survival randomization till death
Trial Locations
- Locations (39)
Edinburgh Cancer Centre at Western General Hospital
🇬🇧Edinburgh, Scotland, United Kingdom
Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, S.A.
🇵🇹Lisbon, Portugal
Inselspital Bern
🇨ðŸ‡Bern, Switzerland
Centre Hospitalier Universitaire Vaudois
🇨ðŸ‡Lausanne, Switzerland
Uppsala University Hospital
🇸🇪Uppsala, Sweden
Institut Bergonie
🇫🇷Bordeaux, France
Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
🇫🇷Montpellier, France
Institute of Oncology - Ljubljana
🇸🇮Ljubljana, Slovenia
Swiss Institute for Applied Cancer Research
🇨ðŸ‡Bern, Switzerland
Algemeen Ziekenhuis Sint-Augustinus
🇧🇪Wilrijk, Belgium
Centre de Lutte Contre le Cancer Georges-Francois Leclerc
🇫🇷Dijon, France
Centre Henri Becquerel
🇫🇷Rouen, France
Centre Rene Huguenin
🇫🇷Saint Cloud, France
Lund University Hospital
🇸🇪Lund, Sweden
Malmo University Hospital
🇸🇪Malmo, Sweden
Sahlgrenska University Hospital - Molndal at Gothenburg University
🇸🇪Molndal, Sweden
Centre Hospitalier Departemental
🇫🇷La Roche Sur Yon, France
Medical University of Gdansk
🇵🇱Gdansk, Poland
Institut Jules Bordet
🇧🇪Brussels, Belgium
Centre Alexis Vautrin
🇫🇷Vandoeuvre-les-Nancy, France
Sahlgrenska University Hospital at Gothenburg University
🇸🇪Gothenburg (Goteborg), Sweden
Orebro University Hospital
🇸🇪Orebro, Sweden
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
🇵🇱Warsaw, Poland
CHU Liege - Domaine Universitaire du Sart Tilman
🇧🇪Liege, Belgium
Centre Paul Papin
🇫🇷Angers, France
Centre Regional Rene Gauducheau
🇫🇷Nantes-Saint Herblain, France
Onze Lieve Vrouwe Gasthuis
🇳🇱Amsterdam, Netherlands
Daniel Den Hoed Cancer Center at Erasmus Medical Center
🇳🇱Rotterdam, Netherlands
Leiden University Medical Center
🇳🇱Leiden, Netherlands
Centre Paul Strauss
🇫🇷Strasbourg, France
Karolinska University Hospital - Huddinge
🇸🇪Stockholm, Sweden
Royal South Hants Hospital
🇬🇧Southampton, England, United Kingdom
Hospitais da Universidade de Coimbra (HUC)
🇵🇹Coimbra, Portugal
Hopital Cantonal Universitaire de Geneve
🇨ðŸ‡Geneva, Switzerland
Scottish Cancer Therapy Network
🇬🇧Edinburgh, Scotland, United Kingdom
UniversitaetsSpital Zuerich
🇨ðŸ‡Zurich, Switzerland
Northern Centre for Cancer Treatment at Newcastle General Hospital
🇬🇧Newcastle Upon Tyne, England, United Kingdom
Kantonspital Aarau
🇨ðŸ‡Aarau, Switzerland
Ninewells Hospital and Medical School
🇬🇧Dundee, Scotland, United Kingdom