A Phase I Dose Escalation Study of 5-Day Intermittent Oral Lapatinib Therapy With Biomarker Analysis in Patients With HER2-Overexpressing Breast Cancer
- To determine the maximum tolerated dose (MTD) of high-dose lapatinib ditosylate in
patients with HER2-overexpressing advanced or metastatic breast cancer.
- To determine the dose-limiting toxicity of this drug in these patients.
- To determine whether tumor HER2 can be completely inactivated by lapatinib ditosylate
at its MTD in the 5-day schedule.
- To determine whether the total inactivation of HER2 decreases cardiac ejection
OUTLINE: Patients are stratified according to dose level.
Patients receive escalating doses of oral lapatinib ditosylate twice daily on days 1-5 until
the maximum tolerated dose is determined. Courses repeat every 2 weeks in the absence of
disease progression or unacceptable toxicity.
Some patients undergo tumor tissue and blood sample collection periodically for biological
and correlative studies. Samples are analyzed for evidence of cardiac injury, tumor target
lysis effects, and to determine if the lapatinib serum levels result in the inactivation of
tumor HER2 and HER3 kinase and oncogenic signaling.
After completion of study treatment, patients are followed every 2 months.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of Lapatinib
Dose Escalation of 5-Day Intermittent Oral Lapatinib Therapy With Biomarker Analysis in Patients With HER2-Overexpressing Breast Cancer
estimated to be 12 months
Mark M. Moasser, MD
University of California, San Francisco
United States: Food and Drug Administration
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|