An Open Label Dose Escalation Safety Study of Convection-Enhanced Delivery of IL13-PE38QQR in Patients With Progressive Pediatric Diffuse Infiltrating Brainstem Glioma and Supratentorial High-Grade Glioma
Objective: The primary purpose of this study is to test the safety and feasibility of
giving a new experimental agent, called IL13-PE38QQR, directly into regions of the brain in
patients with diffusely infiltrating pontine glioma (DIPG) or with recurrent or progressive
supratentorial high-grade glioma (HGG) using a technique called convection-enhanced delivery
or CED. CED uses continuous pressure to push large molecules through the membranes
protecting the brain to reach brain tumors. At the same time, we can watch where the
molecules go in the brain by attaching a tracer, gadolinium-DTPA, to the IL13-PE38QQR, which
can then be seen in the brain with magnetic resonance imaging (MRI). Because we do not know
the best dose to use in patients with DIPG or HGG, we will give increasing amounts of
IL13-PE38QQR to small groups of patients with each type of brain tumor, known as a dose
escalation study. Secondary purposes of this study include determining the effects of this
experimental therapy on the tumor, and evaluating the physical changes in the tumor before
and after the therapy.
Study Population: Twenty pediatric patients with recurrent or progressive DIPG or
supratentorial HGG that have undergone standard treatment and who meet all the Inclusion and
Exclusion Criteria may be enrolled. Eighteen patients will receive treatment; an additional
two patients may be screening failures or unevaluable.
Design: We propose a Phase I single institution, open label, dose escalation (doses of
0.125, 0.25 and 0.5 micrograms/ml), safety and tolerability study of IL13-PE38QQR infused
via CED into patients with either DIPG (up to 9 patients) or recurrent HGG (up to 9
patients). IL13-PE38QQR will be administered to regions of tumor determined by radiographic
findings. Escalating dose levels will be evaluated in the following dose cohorts (3
patients per Cohort): Cohort 1 = 0.125 micrograms/ml, Cohort 2 = 0.25 micrograms/ml and
Cohort 3 = 0.5 micrograms/ml.
Outcome Measures: To assess the safety, tolerability and potential efficacy of CED of
IL13-PE38QQR, we will use detailed clinical and radiographic examinations. These will be
performed at baseline and on post-infusion days 1, 28 and 60. After post-infusion day 60,
clinical and radiographic studies will then be performed every 8 weeks until imaging or
clinical evidence of recurrence/progressive disease or new treatment is initiated.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
1) Feasibility of perfusing specific sites within the CNS with IL13-PE38QQR, administered concurrently with gd-DTPA, 2) Safety and tolerability of escalating doses of IL13-PE38QQR via CED to pediatric patient with DIPGs and HGGs
John D Heiss, M.D.
National Institute of Neurological Disorders and Stroke (NINDS)
United States: Federal Government
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