Phase I Trial of the Combination of Dasatinib and Lapatinib
- Determine the maximum tolerated dose of dasatinib combined with lapatinib ditosylate.
- Describe the toxicities associated with this treatment combination.
- Assess the pharmacokinetic interaction of lapatinib ditosylate and dasatinib.
- Assess the effect of the lapatinib ditosylate and dasatinib combination on circulating
tumor cells and on osteoclast precursor activation.
- Study the association of clinical (toxicity and/or tumor response or activity) with the
pharmacokinetic parameters, and/or biologic (pharmacodynamic) results.
- Describe the responses of this treatment combination.
OUTLINE: This is a multicenter study.
- Cohort I (determination of maximum tolerated dose [MTD]): Patients receive oral
dasatinib and oral lapatinib ditosylate once daily on days 1-28. Courses repeat every
28 days in the absence of disease progression or unacceptable toxicity.
- Cohort II (treatment at the MTD): Patients receive oral dasatinib once daily on days 1
and 9-28, and oral lapatinib ditosylate once daily on days 2-28 of course 1. For all
subsequent courses, patients receive oral dasatinib and oral lapatinib ditosylate once
daily on days 1-28. Courses repeat every 28 days in the absence of disease progression
or unacceptable toxicity.
Tissue and blood samples are collected periodically for pharmacokinetic and correlative
studies. Samples are analyzed for biomarkers, circulating tumor cells, tyrosine
phosphorylated or total MAP-K, EGFR, Her2, and FAK, among other potential markers of
activity and/or response by immunofluorescence. Circulating osteoclasts are also assessed by
After completion of treatment study, patients are followed for 3 months.
Primary Purpose: Treatment
Maximum tolerated dose
Charles Erlichman, MD
United States: Food and Drug Administration
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