Phase I/II Trial of Intracerebral IL13-PE38QQR Infusions in Pediatric Patients With Recurrent Malignant Glioma

PHASE I OBJECTIVES:

I. To describe toxicities and estimate the maximum safe flow rate and maximum tolerated
infusion concentration, of IL13-PE38QQR delivered after surgical resection by peritumoral
infusion via 2 to 4 catheters positioned in the brain adjacent to the resection cavity, from
the start of infusion through the DLT observation period.

II. To determine the IL13 receptor alpha-2 chain expression status and distribution in
pediatric recurrent or progressive malignant gliomas.

III. To describe the overall safety and tolerability of IL13PE38QQR infusion from the start
of infusion through disease progression or initiation of alternative treatment.

PHASE II OBJECTIVES:

I. To estimate the survival distribution post initial progression, at the maximum safe total
flow rate and MTiC established in phase I.

II. To estimate the progression-free survival distribution for patients post-initial
progression or recurrence at the maximum safe total flow rate and MTiC established in phase
I.

III. To determine the serum levels of IL13-PE38QQR and distribution in pediatric recurrent
or progressive malignant gliomas.

IV. To describe the overall safety and tolerability of IL13-PE38QQR infusion from the start
of infusion through disease progression or initiation of alternative treatment.

PROTOCOL OUTLINE: At study entry, all patients will be registered prior to planned gross
total resection (> 95% resection of the solid, contrast enhancing tumor component). On the
day of catheter placement (CP, 2-7 days after resection), if the patient is neurologically
stable, 2-4 catheters will be stereotactically placed. On day 1 after catheter placement,
infusion of IL3-PE38QQR will begin if the patient is neurologically stable and will continue
for 96 hours. In Phase I, the total flow rate and the concentration of IL3-PE38QQR will be
determined by the dose escalation plan. In the Phase II evaluations of safety and efficacy,
patients will be treated at the flow rate and concentration identified in Phase I.

PROJECTED ACCRUAL: Approximately 24 patients will participate in the Phase I portion of the
study. During the Phase I portion, the rate-limiting factor is the time the study must be
closed during the toxicity assessment period. Although it is estimated that 1.5 patients per
month will enroll in the Phase I portion, the observed rate may be lower due to temporary
suspensions in accrual. It is not possible to estimate the time required to complete the
Phase I portion of the trial. It is estimated that approximately 26 patients will contribute
to the Phase II portion. Using the same rough estimate of accrual, the Phase II portion may
last about 3 years.