This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.ABSTRACTHYPOTHESISERBB signal inhibitors will have anti-tumor activity in a variety of pediatric brain tumors, including medulloblastomas/PNETs, high-grade gliomas, and ependymomas.
SPECIFIC AIMS Primary1. To estimate the MTD and describe the DLT of oral lapatinib (GW572016) administered twice daily for 28 days to children with recurrent or refractory malignant brain tumors who are not receiving steroids (Stratum 1) and to describe toxicities in those who are receiving steroids (Stratum 2).2. To test the ability of lapatinib (GW572016) to inhibit ERBB receptor signaling in recurrent or refractory: medulloblastoma P/NET, high-grade glioma or ependymomas.3. To estimate the sustained objective response rates (CR plus PR) to lapatinib (GW572016) administered continuously at the MTD to childrenwith recurrent or refractory:medulloblastoma/PNET, high-grade glioma or ependymoma. Independent estimates of the ojbective response rates will be made for each of these three histologically defined strata.Secondary4. To characterize the plasma and tissue pharmacokinetics of lapatinib (GW5720196) in children.5. To assess the effect of steroids on the pharmacokinetics of lapatinib (GW572016).6. To explore the pharmacogenetic polmorphisms in lapatinib (GW572016) metabolizing enzymes and relate these polymorphisms to the drug pharmacokinetics.7. To estimate the incidence of ERBB1, ERBB2, ERBB3 and ERBB4 expression and pathway activation in recurent or refractory CNS tumors of childhood, including ependymoma, medulloblastoma/PNET and glioma.8. To identily additional genes both within and outside the canonical ERBB pathway that might act as determinants of response to lapatinib (GW572016)
Showing the most recent 10 out of 459 publications