Ignite Creation Date:
2024-05-05 @ 11:23 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00017095
Status:
COMPLETED
Last Update Posted:
2013-10-24
First Post:
2001-06-06
Brief Title:
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
Sponsor:
European Organisation for Research and Treatment of Cancer - EORTC
Organization:
European Organisation for Research and Treatment of Cancer - EORTC
Study Overview
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 AdvancedInflammatory or Large Operable Breast Cancer Prospectively Randomised to a Taxane Versus a Non Taxane Regimen
Status:
COMPLETED
Status Verified Date:
2013-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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- andor 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 15 years and then every 6 months thereafter
PROJECTED ACCRUAL A total of 1850 patients will be accrued for this study within 55 years
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- andor 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 15 years and then every 6 months thereafter
PROJECTED ACCRUAL A total of 1850 patients will be accrued for this study within 55 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| BIG-1-00 | None | None | None |
| EORTC-10994 | None | None | None |
| ACCOG-EORTC-10994 | None | None | None |
| SAKK-EORTC-10994 | None | None | None |
| SBGC-EORTC-10994 | None | None | None |