Phase I/II Trial Of Intracerebral IL13-PE38QQR Infusions In Pediatric Patients With Recurrent Malignant Glioma
- Determine the toxicity of peritumoral IL13-PE38QQR after surgical resection in
pediatric patients with recurrent malignant gliomas. (Phase I)
- Determine the maximum tolerated flow rate and maximum tolerated infusion concentration
(MTiC) of this drug in these patients. (Phase I)
- Estimate the rate of survival after initial progression in patients treated at the
maximum safe flow rate and MTiC with this drug. (Phase II)
- Describe the overall safety and tolerability of this regimen in these patients from the
start of infusion through disease progression or initiation of alternative treatment.
- Determine the IL13 receptor α2 chain expression status and distribution in pediatric
recurrent or progressive malignant gliomas
- Estimate the progression-free survival of patients treated with this drug. (Phase II)
OUTLINE: This is a multicenter, dose-escalation study.
- Phase I: Patients undergo surgical resection of the tumor. Within 2-7 days later,
patients undergo placement of 2-4 peritumoral catheters. One to 2 days later, patients
receive peritumoral IL13-PE38QQR continuously over 96 hours. Catheters are removed
after completion of the infusion.
Cohorts of 3 patients receive IL13-PE38QQR at escalating flow rates and a fixed
concentration until the maximum safe flow rate is determined. The maximum safe flow rate is
defined as the rate prior to the one at which 2 of 3 or more patients experience
Following determination of the maximum safe flow rate, cohorts of 2-3 patients receive
IL13-PE38QQR at escalating concentrations at the maximum safe flow rate until the maximum
tolerated infusion concentration (MTiC) is determined. The MTiC is defined as the
concentration prior to the one at which 2 of 3 or more patients experience dose-limiting
- Phase II: Patients receive IL13-PE38QQR as above at the maximum safe flow rate and MTiC
determined in the phase I of the study.
Patients are followed at week 18 after catheter placement and then every 8 weeks thereafter
until death, disease progression, or completion of six months (phase I) or 12 months (phase
II) of follow-up after the end of IL13-PE38QQR infusion. Phase II patients who complete one
year of follow-up without disease progression are followed every 12 weeks thereafter until
PROJECTED ACCRUAL: Approximately 2-50 patients (2-24 for phase I and approximately 26 for
phase II) will be accrued for this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Toxicities from the start of infusion through the dose limiting toxicity observation period(Phase I)
Toxicities reported are those occurring from the start of the IL13 infusion after catheter placement to Day 35 (30 days after the end of the infusion) if there are no or mild MRI changes on Day 35 around the catheter tract or tip. If the MRI change on Day 35 indicates moderate or extensive changes around the catheter tract or tip then the toxicities reported are those occurring from the start of the IL13 infusion to Day 75 (70 days after the end of the infusion).
Start of IL13-PE38QQR infusion to Day 35 or Day 75
Anuradha Banerjee, MD
University of California, San Francisco
United States: Food and Drug Administration