TP-38 Toxin in Treating Young Patients With Recurrent or Progressive Supratentorial High-Grade Glioma
- Conditions
- Brain and Central Nervous System Tumors
- Registration Number
- NCT00074334
- Lead Sponsor
- Pediatric Brain Tumor Consortium
- Brief Summary
RATIONALE: The TP-38 toxin can locate tumor cells and kill them without harming normal cells. Giving TP-38 toxin directly into the tumor may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of TP-38 toxin administered directly into the brain and to see how well it works in treating young patients with recurrent or progressive supratentorial high-grade glioma.
- Detailed Description
OBJECTIVES:
Primary
* Phase I
* Determine the maximum safe volume rate and maximum tolerated infusion concentration of TGFa-PE38 toxin (TP-38) infused through 2 or 3 catheters in pediatric patients with recurrent or progressive supratentorial high-grade glioma.
* Describe the toxic effects of this drug in these patients.
* Phase II
* Estimate the efficacy of this drug, in terms of post-infusion survival, in these patients.
Secondary
* Phase I and II
* Determine the prevalence of epidermal growth factor receptor (EGFR) expression and phosphorylation (activity) in patients treated with this drug.
* Correlate EGFR expression with qualitative measures (e.g., histology, grade, and other tumor characteristics) and tumor response, survival, and progression-free survival in patients treated with this drug.
* Phase II Only
* Estimate the objective response rate in patients treated with this drug.
* Estimate the progression-free survival of patients treated with this drug.
OUTLINE: This is a dose-escalation, multicenter study. Patients in the phase I portion of the study are stratified according to the number of successfully placed catheters (3 catheters vs 2 catheters). Patients in the phase II portion of the study are stratified according to time of recurrence of high-grade glioma (first vs second or greater) and by surgery extent (surgical resection vs stereotactic biopsy) for those with first recurrence only.
* Phase I: Patients undergo stereotactic biopsy or resection of the tumor followed by intratumoral (or tumor bed) catheter placement for treatment infusion. Within 12-48 hours after intratumoral (or tumor bed) catheter placement, patients receive TGFa-PE38 toxin (TP-38) intratumorally through 2 or 3 catheters over 33 to 124 hours. Treatment continues in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients (in each stratum) receive escalating volumes until the maximum safe volume (MSV) is determined. Cohorts of 3-6 patients (in each stratum) receive escalating concentrations at the MSV until the maximum tolerated infusion concentration (MTIC) is determined. The MSV and MTIC are defined as the volume and concentration preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
* Phase II: Patients receive treatment as in phase I at the MSV and MTIC.
Phase I patients are followed post catheter placement, daily during TP-38 infusion, at 30 days, and then every 2 months for 1 year. Phase II patients will be followed for an additional year.
PROJECTED ACCRUAL: A total of 6-105 patients (6-60 for phase I and 45 for phase II) will be accrued for this study.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 3
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Maximum tolerated infusion concentration of TP-38 infused through three catheters (Stratum A) or through two catheters (Stratum B). Toxicities of TP-38 Post-infusion survival (phase II) Maximum safe volume rate of TP-38 infused through three catheters (Stratum A) or through two catheters (Stratum B).
- Secondary Outcome Measures
Name Time Method EGFR expression and phosphorylation (activity) Correlation of EGFR expression with tumor histology, tumor grade, tumor response (phase I and phase II) and survival and progression-free survival (phase II). Post-infusion progression-free survival (phase II) Objective response (phase II)
Trial Locations
- Locations (8)
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Children's Memorial Hospital - Chicago
🇺🇸Chicago, Illinois, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Abramson Cancer Center of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Duke Comprehensive Cancer Center
🇺🇸Durham, North Carolina, United States
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
🇺🇸Houston, Texas, United States