ABT-888 and Temozolomide in Treating Young Patients With Recurrent or Refractory CNS Tumors

PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) of ABT-888 in combination with temozolomide in children with recurrent or refractory CNS tumors. II. To study the plasma pharmacokinetics (PK) of ABT-888 and PARP inhibition in peripheral blood mononuclear cells (PBMC) in order to recommend a Phase 2 dose of ABT-888 in combination with temozolomide in children with recurrent or refractory CNS tumors. III. To describe the toxicities of the combination of ABT-888 and temozolomide in children with recurrent or refractory CNS tumors. SECONDARY OBJECTIVES: I. To measure non-homologous end-joining (NHEJ) activity in peripheral blood mononuclear cells (PBMC) prior to and following ABT-888 administration. II. To assess PARP expression and/or activity in tumor tissue obtained at either initial diagnosis or relapse. III. To determine expression and/or activity of DNA repair pathways, including MGMT and mismatch repair, in tumor tissues, when available. IV. To document, within the confines of this phase 1 trial, radiographic tumor response to ABT-888 and temozolomide. OUTLINE: This is a dose-escalation study of ABT-888. Patients receive oral ABT-888 twice daily and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for 13-26 courses in the absence of disease progression or unacceptable toxicity. Blood samples are collected for pharmacokinetics and further laboratory analysis.