PTC299 in Treating Young Patients With Refractory or Recurrent Primary Central Nervous System Tumors
Condition: Brain and Central Nervous System Tumors
MeSH terms: Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: PTC299 may stop the growth of tumor cells by blocking blood flow to the tumor.

      PURPOSE: This phase I trial is studying the side effects and the best dose of PTC299 in
      treating young patients with recurrent or refractory primary central nervous system tumors.
    

Detailed description: 
      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.
    

Intervention name(s): VEGF inhibitor PTC299
Intervention type(s): Drug
Intervention description(s): This is a dose escalation study. Study participants will receive .6 or 1.2 mg/kg orally twice daily or 1.2, 1.5, or 2.0 mg/kg orally three times daily for four consecutive weeks (a course). In the absence of unacceptable toxicity or disease progression, treatment may continue for up to 12 courses (approximately one year)
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent childhood malignant germ cell tumor; recurrent childhood brain stem glioma; recurrent childhood brain tumor; recurrent childhood central nervous system embryonal tumor; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma; recurrent childhood ependymoma; recurrent childhood medulloblastoma; recurrent childhood pineoblastoma; recurrent childhood rhabdomyosarcoma; recurrent childhood spinal cord neoplasm; recurrent childhood subependymal giant cell astrocytoma; recurrent childhood visual pathway and hypothalamic glioma; recurrent childhood visual pathway glioma; childhood central nervous system choriocarcinoma; childhood central nervous system germ cell tumor; childhood central nervous system germinoma; childhood central nervous system mixed germ cell tumor; childhood central nervous system teratoma; childhood central nervous system yolk sac tumor; childhood astrocytoma; childhood medulloepithelioma; childhood meningioma; childhood mixed glioma; childhood oligodendroglioma; childhood pineal parenchymal tumor