PTC299 in Treating Young Patients With Refractory or Recurrent Primary Central Nervous System Tumors
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.
Brain and Central Nervous System Tumors
Drug: VEGF inhibitor PTC299
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I and Pharmacokinetic Trial of PTC299 in Pediatric Patients With Refractory or Recurrent CNS Tumors|
- Maximum-tolerated dose [ Time Frame: First four weeks of treatment ] [ Designated as safety issue: Yes ]
- Adverse events [ Time Frame: From the first day of treatment until 30 days after the last dose ] [ Designated as safety issue: Yes ]
- Percentage of study participants with complete response or partial response to the study treatment [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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.
|Study Start Date:||November 2010|
|Study Completion Date:||January 2015|
|Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
Drug: VEGF inhibitor PTC299
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01158300
|United States, California|
|UCSF Cancer Center and Cancer Research Institute|
|San Francisco, California, United States, 94143-0128|
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010-2970|
|United States, Illinois|
|Children's Memorial Hospital - Chicago|
|Chicago, Illinois, United States, 60614|
|United States, North Carolina|
|Duke Comprehensive Cancer Center|
|Durham, North Carolina, United States, 27710|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104-4318|
|Children's Hospital of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, Tennessee|
|St. Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105|
|United States, Texas|
|Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital|
|Houston, Texas, United States, 77030-2399|
|Principal Investigator:||Roger J. Packer, MD||Children's Research Institute|