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.ABSTRACTHYPOTHESIS: SAHA will be well-tolerated both as a single agent and in combination with cis-retinoic acid in children with recurrent or refractory cancer.
SPECIFIC AIMS Primary Aims: To estimate the maximum tolerated dose (MTD) of SAHA administered once daily orally for 28 days to children with refractory or recurrent solid tumors.To estimate the maximum tolerated dose (MTD) of SAHA administered once daily orally for 28 days in combination with 13-cis retinoic acid to children with refractory or recurrent neuroblastoma, medulloblastoma/CNS neuroectodermal tumor (PNET) or atypical teratoid rhabdoid tumor (ATRT).To assess the tolerability of the solid tumor MTD in patients with recurrent or refractory leukemia.To define and describe the toxicities of SAHA administered on this schedule as a single agent and in combination with 13 cis-retinoic acid.To characterize the pharmacokinetics of SAHA in children with refractory cancer.Secondary Aims:To preliminarily define the antitumor activity of SAHA as a single agent and in combination with 13-cis retinoic acid within the confines of a Phase I study.To assess the biologic activity of SAHA by measuring histone acetylation status in peripheral mononuclear cells (PMNC) and tumor tissue specimens.To explore the effect of genetic polymorphisms (e.g., UGTIA1) on the pharmacokinetics of SAHA.
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