Phase II Study of Cardiac Safety and Tolerability of an Adjuvant Chemotherapy Plus Trastuzumab With Lapatinib in Patients With Resected HER2 + Breast Cancer
- 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.
- Determine the adverse event profile of this regimen in these patients.
- Determine the cumulative incidence of cardiac events in patients treated with this
- 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
- 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
- Evaluate cardiac markers (i.e., 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 patterns/molecular signatures and
- Determine the time course of these molecular signatures and evaluate whether they are
accurate predictors of cardiotoxicity that precede other evidence of cardiotoxicity
(e.g., changes in left ventricular function seen by echocardiogram or MUGA scan).
- Compare metabolic signatures of cardiotoxicity with known laboratory evidence of
cardiac damage (e.g., troponins or brain natriuretic peptide) in terms of sensitivity
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
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.
Allocation: Randomized, Primary Purpose: Treatment
Number of Patients With Congestive Heart Failure (CHF) While on Active Treatment
Edith A. Perez, MD
Mayo Clinic in Florida
United States: Food and Drug Administration
|Mayo Clinic Cancer Research Consortium||Rochester, Minnesota 55905|