Finding studies
Finding studies
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Lead
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
With
OBJECTIVES: Primary * To determine the maximum tolerated dose (MTD) of ABT-888 when administered in combination with radiotherapy and temozolomide in patients with newly diagnosed glioblastoma multiforme. (Phase I) * To estimate the overall survival of patients treated with ABT-888 when administered at the MTD in combination with radiotherapy and temozolomide. (Phase II) Secondary * To assess the toxicity associated with this regimen. (Phase I) * To assess and describe the pharmacokinetics of ABT-888. (Phase I) * To estimate the frequency of toxicity associated with this regimen. (Phase II) OUTLINE: This is a multicenter, phase I dose-escalation study of ABT-888 followed by a phase II study. * Initiation therapy: Patients receive oral ABT-888 twice daily (once on day 1 only) and oral temozolomide once daily (beginning on day 2) in weeks 1-6. Patients enrolled in the phase I dose-escalation/phase II portion of the study also undergo concurrent radiotherapy once daily 5 days a week (beginning on day 2) in weeks 1-6. Treatment continues in the absence of disease progression or unacceptable toxicity. * Maintenance therapy: Beginning 4 weeks after completion of initiation therapy, patients receive oral ABT-888 twice daily on days 1-7 and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 4 courses (6 courses for patients enrolled in the phase I dose-escalation/phase II portion of the study) in the absence of disease progression or unacceptable toxicity. Blood samples are collected periodically for pharmacokinetic, pharmacogenetic, and pharmacodynamic analysis. Samples are analyzed for concentration of ABT-888 in plasma by reversed-phase isocratic high performance liquid chromatography with electrospray ionization mass spectrometry; identification of novel markers of treatment response by plasma proteomic evaluation; DNA methylation and/or mutation; and PARP inhibition by ELISA. After completion of study therapy, patients are followed every 2 months.
Age
18–120
Sex
ALL
Healthy volunteers
Not accepted
