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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase I and Pharmacokinetic Trial of PTC299 in Pediatric Patients With Refractory or Recurrent CNS Tumors

Brief 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 Summary:

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
Sponsor: Pediatric Brain Tumor Consortium

Current Primary Outcome:

  • Maximum-tolerated dose [ Time Frame: First four weeks of treatment ]
  • Adverse events [ Time Frame: From the first day of treatment until 30 days after the last dose ]


Original Primary Outcome:

  • Maximum-tolerated dose
  • Adverse events
  • Pharmacokinetics
  • Pharmacodynamics


Current Secondary Outcome:

  • Percentage of study participants with complete response or partial response to the study treatment [ Time Frame: Every 8 weeks ]
    Brain images to assess partial or complete response are performed every 8 weeks after the first dose of the study drug.
  • Pharmacokinetics [ Time Frame: Day 1 and day 28 of course 1 ]
    Blood samples from study participants will be collected on day 1 and day 28 of course 1 for standard full pharmacokinetic studies.
  • Change from baseline in blood angiogenic markers and cytokines at discontinuation or completion of treatment [ Time Frame: Before the first dose of drug on day 1 of course 1 and at the discontinuation or completion of treatment ]
    Blood samples will be collected and analyzed on Day 1 of pre-AM dosing at baseline and at the discontinuation or completion of treatment. Changes from baseline in blood angiogenic markers and cytokines (VEGF-A, VEGF-C, VEGF-D, PlGF, VEGFR-1, VEGFR-2, IL-6, and IL-8) will be assessed.


Original Secondary Outcome: Response

Information By: Pediatric Brain Tumor Consortium

Dates:
Date Received: July 7, 2010
Date Started: November 2010
Date Completion:
Last Updated: May 1, 2015
Last Verified: May 2015