PTC299 in Treating Young Patients With Refractory or Recurrent Primary Central Nervous System Tumors

OBJECTIVES:

Primary

- To estimate the maximum-tolerated dose and the recommended phase II dose of VEGF
inhibitor PTC299 (PTC299) in pediatric patients with recurrent or progressive primary
central nervous system (CNS) tumors.

- To evaluate and characterize the adverse events associated with this regimen in these
patients.

- To evaluate and characterize the pharmacokinetics and pharmacodynamics of this regimen
in these patients.

Secondary

- To investigate the relationships between PTC299 plasma exposure and other outcomes
measures.

- To evaluate the antitumor activity of this regimen in these patients.

- To evaluate changes in angiogenic and inflammatory markers in the blood and the
relationship between these changes and other outcome measures.

- To obtain preliminary evidence of biologic activity of PTC299 by using magnetic
resonance diffusion to assess tumor cellularity.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive oral VEGF inhibitor PTC299 twice or thrice daily. Treatment repeats every
28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and periodically during study for pharmacokinetic
and pharmacodynamic studies by ELISA.

After completion of study therapy, patients are followed up for 30 days.