Ignite Creation Date:
2024-05-05 @ 5:19 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00436566
Status:
COMPLETED
Last Update Posted:
2022-08-05
First Post:
2007-02-15
Brief Title:
Doxorubicin and Cyclophosphamide Followed By Trastuzumab Paclitaxel and Lapatinib in Treating Patients With Early-Stage HER2-Positive Breast Cancer That Has Been Removed By Surgery
Sponsor:
Mayo Clinic
Organization:
Mayo Clinic
Study Overview
Official Title:
Phase II Study of Cardiac Safety and Tolerability of an Adjuvant Chemotherapy Plus Trastuzumab With Lapatinib in Patients With Resected HER2 Breast Cancer
Status:
COMPLETED
Status Verified Date:
2019-01
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 such as doxorubicin cyclophosphamide and paclitaxel work in different ways to stop the growth of tumor cells either by killing the cells or by stopping them from dividing Monoclonal antibodies such as trastuzumab can block tumor growth in different ways Some block the ability of tumor cells to grow and spread Others find tumor cells and help kill them or carry tumor-killing substances to them Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth Giving combination chemotherapy together with trastuzumab and lapatinib after surgery may kill any tumor cells that remain after surgery
PURPOSE This randomized phase II trial is studying the side effects and how well giving doxorubicin together with cyclophosphamide followed by trastuzumab paclitaxel and lapatinib works in treating patients with early-stage HER2-positive breast cancer that has been removed by surgery
PURPOSE This randomized phase II trial is studying the side effects and how well giving doxorubicin together with cyclophosphamide followed by trastuzumab paclitaxel and lapatinib works in treating patients with early-stage HER2-positive breast cancer that has been removed by surgery
Detailed Description:
OBJECTIVES
Primary
Determine the cardiac safety of adjuvant therapy comprising doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel trastuzumab Herceptin and lapatinib ditosylate in patients with resected early-stage HER2-positive breast cancer
Secondary
Determine the adverse event profile of this regimen in these patients
Determine the cumulative incidence of cardiac events in patients treated with this regimen
Determine the LVEF in patients treated with this regimen
Determine the disease-free and overall survival of patients treated with this regimen
Compare selected quality-of-life QOL questionnaires in these patients
Evaluate QOL of patients treated with this regimen
Determine the cumulative incidence of pulmonary events in patients treated with this regimen
Tertiary
Compare Veridex CellSearch system vs quantitative reverse transcriptase polymerase chain reaction for detecting circulating tumor cells
Determine the relationship between serum levels of HER1 and HER2 and response to treatment
Evaluate cardiac markers ie troponin-T troponin-I brain natriuretic peptide and creatine kinase MB isoenzyme at baseline
Determine the association between abnormal levels of cardiac markers and incidence of cardiac adverse events
Evaluate patterns of 500 metabolites in plasma in patients treated with this regimen and determine the association between metabolite patternsmolecular signatures and cardiotoxicity
Determine the time course of these molecular signatures and evaluate whether they are accurate predictors of cardiotoxicity that precede other evidence of cardiotoxicity eg changes in left ventricular function seen by echocardiogram or MUGA scan
Compare metabolic signatures of cardiotoxicity with known laboratory evidence of cardiac damage eg troponins or brain natriuretic peptide in terms of sensitivity and specificity
OUTLINE This is a randomized pilot multicenter study Patients are stratified according to educational level less than high school vs high school or GED vs formal education beyond high school
Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 Treatment repeats every 2-3 weeks for 4 courses Patients then receive paclitaxel IV over 60 minutes and trastuzumab Herceptin IV over 90 minutes on days 1 8 and 15 and oral lapatinib ditosylate on days 1-21 Treatment with paclitaxel trastuzumab and lapatinib repeats every 3 weeks for up to 4 courses Patients then receive trastuzumab IV over 30-90 minutes on day 1 and oral lapatinib ditosylate on days 1-21 Treatment with trastuzumab and lapatinib ditosylate repeats every 3 weeks for up to 12 courses
Patients complete Linear Anologue Self Assessment LASA and Symptoms Distress Scale SDS questionnaires including fatigue diarrhea and rash assessment at baseline after 2-3 5-6 and 18 months of treatment and 5 years after completion of treatment Patients are also randomized to 1 of 2 arms to complete additional quality of life questionnaires at these same time points
Arm I Patients complete EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires
Arm II Patients complete FACT-B questionnaire Blood samples are acquired periodically throughout and at the completion of study treatment Samples are analyzed for circulating tumor cells by Veridex CellSearch system quantitative reverse transcriptase polymerase chain reaction and liquid chromatography with tandem mass spectrometry soluble HER1- and HER2-receptor concentrations circulating cardiac markers and metabolic markers for possible correlation with cardiac events
After completion of study treatment patients are followed periodically for up to 10 years
PROJECTED ACCRUAL A total of 109 patients will be accrued for this study
Primary
Determine the cardiac safety of adjuvant therapy comprising doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel trastuzumab Herceptin and lapatinib ditosylate in patients with resected early-stage HER2-positive breast cancer
Secondary
Determine the adverse event profile of this regimen in these patients
Determine the cumulative incidence of cardiac events in patients treated with this regimen
Determine the LVEF in patients treated with this regimen
Determine the disease-free and overall survival of patients treated with this regimen
Compare selected quality-of-life QOL questionnaires in these patients
Evaluate QOL of patients treated with this regimen
Determine the cumulative incidence of pulmonary events in patients treated with this regimen
Tertiary
Compare Veridex CellSearch system vs quantitative reverse transcriptase polymerase chain reaction for detecting circulating tumor cells
Determine the relationship between serum levels of HER1 and HER2 and response to treatment
Evaluate cardiac markers ie troponin-T troponin-I brain natriuretic peptide and creatine kinase MB isoenzyme at baseline
Determine the association between abnormal levels of cardiac markers and incidence of cardiac adverse events
Evaluate patterns of 500 metabolites in plasma in patients treated with this regimen and determine the association between metabolite patternsmolecular signatures and cardiotoxicity
Determine the time course of these molecular signatures and evaluate whether they are accurate predictors of cardiotoxicity that precede other evidence of cardiotoxicity eg changes in left ventricular function seen by echocardiogram or MUGA scan
Compare metabolic signatures of cardiotoxicity with known laboratory evidence of cardiac damage eg troponins or brain natriuretic peptide in terms of sensitivity and specificity
OUTLINE This is a randomized pilot multicenter study Patients are stratified according to educational level less than high school vs high school or GED vs formal education beyond high school
Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 Treatment repeats every 2-3 weeks for 4 courses Patients then receive paclitaxel IV over 60 minutes and trastuzumab Herceptin IV over 90 minutes on days 1 8 and 15 and oral lapatinib ditosylate on days 1-21 Treatment with paclitaxel trastuzumab and lapatinib repeats every 3 weeks for up to 4 courses Patients then receive trastuzumab IV over 30-90 minutes on day 1 and oral lapatinib ditosylate on days 1-21 Treatment with trastuzumab and lapatinib ditosylate repeats every 3 weeks for up to 12 courses
Patients complete Linear Anologue Self Assessment LASA and Symptoms Distress Scale SDS questionnaires including fatigue diarrhea and rash assessment at baseline after 2-3 5-6 and 18 months of treatment and 5 years after completion of treatment Patients are also randomized to 1 of 2 arms to complete additional quality of life questionnaires at these same time points
Arm I Patients complete EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires
Arm II Patients complete FACT-B questionnaire Blood samples are acquired periodically throughout and at the completion of study treatment Samples are analyzed for circulating tumor cells by Veridex CellSearch system quantitative reverse transcriptase polymerase chain reaction and liquid chromatography with tandem mass spectrometry soluble HER1- and HER2-receptor concentrations circulating cardiac markers and metabolic markers for possible correlation with cardiac events
After completion of study treatment patients are followed periodically for up to 10 years
PROJECTED ACCRUAL A total of 109 patients will be accrued for this study
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 |
|---|---|---|---|
| 06-004049 | OTHER | Mayo Clinic IRB | httpsreporternihgovquickSearchP30CA015083 |
| P30CA015083 | NIH | None | None |
| RC0639 | OTHER | None | None |