A Phase I Dose Escalation Study of 5-Day Intermittent Oral Lapatinib Therapy With Biomarker Analysis in Patients With HER2-Overexpressing Breast Cancer

Brief Summary

Detailed Description

OBJECTIVES: Primary * 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. Secondary * 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 fraction. 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.

Primary Outcomes