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
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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 |
- Progression-free survival [ Time Frame: from randomization till first evidence of progression ] [ Designated as safety issue: No ]
- 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 |
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
Hide Study Locations| Belgium | |
| Institut Jules Bordet | |
| Brussels, Belgium, 1000 | |
| CHU Liege - Domaine Universitaire du Sart Tilman | |
| Liege, Belgium, B-4000 | |
| Algemeen Ziekenhuis Sint-Augustinus | |
| Wilrijk, Belgium, 2610 | |
| France | |
| Centre Paul Papin | |
| Angers, France, 49036 | |
| Institut Bergonie | |
| Bordeaux, France, 33076 | |
| Centre de Lutte Contre le Cancer Georges-Francois Leclerc | |
| Dijon, France, 21079 | |
| Centre Hospitalier Departemental | |
| La Roche Sur Yon, France, F-85025 | |
| Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle | |
| Montpellier, France, 34298 | |
| Centre Regional Rene Gauducheau | |
| Nantes-Saint Herblain, France, 44805 | |
| Centre Henri Becquerel | |
| Rouen, France, 76038 | |
| Centre Rene Huguenin | |
| Saint Cloud, France, 92211 | |
| Centre Paul Strauss | |
| Strasbourg, France, 67085 | |
| Centre Alexis Vautrin | |
| Vandoeuvre-les-Nancy, France, 54511 | |
| Netherlands | |
| Onze Lieve Vrouwe Gasthuis | |
| Amsterdam, Netherlands, 1091 HA | |
| Leiden University Medical Center | |
| Leiden, Netherlands, 2300 CA | |
| Daniel Den Hoed Cancer Center at Erasmus Medical Center | |
| Rotterdam, Netherlands, 3008 AE | |
| Poland | |
| Medical University of Gdansk | |
| Gdansk, Poland, 80-211 | |
| Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology | |
| Warsaw, Poland, 02-781 | |
| Portugal | |
| Hospitais da Universidade de Coimbra (HUC) | |
| Coimbra, Portugal, 3049 | |
| Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, S.A. | |
| Lisbon, Portugal, 1099-023 Codex | |
| Slovenia | |
| Institute of Oncology - Ljubljana | |
| Ljubljana, Slovenia, Sl-1000 | |
| Sweden | |
| Sahlgrenska University Hospital at Gothenburg University | |
| Gothenburg (Goteborg), Sweden, S-413 45 | |
| Lund University Hospital | |
| Lund, Sweden, S-22185 | |
| Malmo University Hospital | |
| Malmo, Sweden, S-20502 | |
| Sahlgrenska University Hospital - Molndal at Gothenburg University | |
| Molndal, Sweden, S-43180 | |
| Orebro University Hospital | |
| Orebro, Sweden, 70185 | |
| Karolinska University Hospital - Huddinge | |
| Stockholm, Sweden, S-171 76 | |
| Uppsala University Hospital | |
| Uppsala, Sweden, S-75185 | |
| Switzerland | |
| Kantonspital Aarau | |
| Aarau, Switzerland, 5001 | |
| Inselspital Bern | |
| Bern, Switzerland, CH-3010 | |
| Swiss Institute for Applied Cancer Research | |
| Bern, Switzerland, CH-3008 | |
| Hopital Cantonal Universitaire de Geneve | |
| Geneva, Switzerland, CH-1211 | |
| Centre Hospitalier Universitaire Vaudois | |
| Lausanne, Switzerland, CH-1011 | |
| UniversitaetsSpital Zuerich | |
| Zurich, Switzerland, CH-8091 | |
| United Kingdom | |
| Northern Centre for Cancer Treatment at Newcastle General Hospital | |
| Newcastle Upon Tyne, England, United Kingdom, NE4 6BE | |
| Royal South Hants Hospital | |
| Southampton, England, United Kingdom, SO14 0YG | |
| Ninewells Hospital and Medical School | |
| Dundee, Scotland, United Kingdom, DD1 9SY | |
| Edinburgh Cancer Centre at Western General Hospital | |
| Edinburgh, Scotland, United Kingdom, EH4 2XU | |
| Scottish Cancer Therapy Network | |
| Edinburgh, Scotland, United Kingdom, EH5 3SQ | |
| Study Chair: | Herve Bonnefoi | Institut Bergonie, Bordeaux |
More Information
Additional Information:
Publications:
| 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: | July 19, 2012 |
| 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 Antimetabolites Antimetabolites, Antineoplastic Adjuvants, Immunologic |
ClinicalTrials.gov processed this record on May 16, 2013