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RATIONALE: Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may help temozolomide work better by making tumor cells more sensitive to the drug.
PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat when given together with temozolomide in treating young patients with relapsed or refractory primary brain tumors or spinal cord tumors.
- To estimate the maximum tolerated dose and/or recommended phase II dose of vorinostat in combination with temozolomide in pediatric patients with relapsed or refractory primary CNS tumors.
- To define and describe the toxicities of this regimen in these patients.
- To preliminarily define the antitumor activity of this regimen within the confines of a phase I study.
- To characterize the pharmacokinetic parameters of vorinostat in these patients.
- To determine whether acetylated histones in peripheral blood mononuclear cells can be identified as a surrogate marker of the biologic effect of vorinostat at various treatment doses.
- To assess the feasibility of collecting and analyzing serum DNA for methylation of the MGMT promoter and describe the relationship between promoter methylation and clinical responses within the confines of this phase I study.
OUTLINE: This is a multicenter, dose-escalation study of vorinostat.
Patients receive oral vorinostat and oral temozolomide once daily on days 1-5. Courses repeat every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
Patients may undergo blood sample collection periodically for pharmacokinetic and correlative laboratory studies by western blotting and MGMT promoter methylation assays.
After completion of study therapy, patients are followed up for 30 days.
Masking: Open Label, Primary Purpose: Treatment
Brain and Central Nervous System Tumors
temozolomide, vorinostat, DNA methylation analysis, western blotting, laboratory biomarker analysis, pharmacological study
UAB Comprehensive Cancer Center
National Cancer Institute (NCI)
Published on BioPortfolio: 2014-07-23T21:09:59-0400
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