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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

Phase 1
17 Years
Open (Enrolling)
Brain Neoplasm, Glioma

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Trial Information

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.

Inclusion Criteria


- Age less than 18 years

- Diagnosis: recurrent or progressive:


2. HGG

- Patients undergoing surgical resection must have measurable/evaluable disease prior
to study entry.

- Histopathologic Diagnosis

1. A histopathologic diagnosis is not required for patients with DIPG but a biopsy
may be recommended if the patient has an atypical presentation or atypical
findings on MR-imaging.

2. Histopathologic confirmation for patients with HGG is required. If necrosis is
suspected based on MR-imaging and Nuclear Medicine scans, biopsy or surgical
resection for confirmation of disease progression may be required.

- Prior Therapy

1. Patients must have received at least standard doses of radiation (i.e., greater
than 54 Gy).

2. Surgery/biopsy - Patients must be more than 2 weeks from any neurosurgical
procedure and cleared by the Principal Investigator before undergoing CED.

3. Radiation - Patients must be more than 4 weeks from last fraction of radiation
to the target site

4. Chemotherapy - Patients must not be on concurrent chemotherapy. The last dose
of chemotherapy must be greater than 2 weeks prior to CED and the patient must
have recovered from any toxic effects of prior therapy (to less than Grade 2 or

5. Biologic therapy - Patients must be greater than 7 days from biologic therapy.

6. Investigational therapy - Patients must be greater than 30 days from any
investigational therapy.

- Patients must be healthy enough to tolerate surgery and general anesthesia in the
opinion of the primary investigator. This includes, but is not limited to:

1. Adequate baseline organ function, including an age-adjusted normal serum
creatinine OR a creatinine clearance greater or equal to 60 mL/min/1.73m(2),
total bilirubin less than 2 times the upper limit of normal (ULN) and direct
bilirubin within normal limits. Patients with elevated SGPT (up to 5 times ULN)
will be eligible if the elevation is attributed to steroid treatment.

2. If neurological deficits are present, they must be stable for at least 1 week
prior to registration.

- Patients must be able to undergo MR-imaging with gadolinium-based contrast
administration (e.g. no ferrous-containing implants, no pacemakers, no allergy to
contrast, etc).

- All patients or their legal guardians must sign a document of informed consent
indicating their understanding of the investigational nature and the potential risks
associated with this study. When appropriate, pediatric patients will be included in
all discussions in order to obtain verbal and written assent.


- Patients with an uncorrectable bleeding disorder

- Patients with multifocal or leptomeningeal disease

- Patients with signs of impending herniation or an acute intratumoral hemorrhage

- Patients on concurrent chemotherapy or biologic therapy for the treatment of their

- Patients who are pregnant or breastfeeding, because of unknown effects of the study
agent, the strong magnetic fields and Gadolinium containing contrast agents on the
fetus; patients of child-bearing potential must be willing to practice an effective
form of birth control, including abstinence, hormone therapy, intrauterine device, 2
barrier methods.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Principal Investigator

John D Heiss, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Institute of Neurological Disorders and Stroke (NINDS)


United States: Federal Government

Study ID:




Start Date:

April 2009

Completion Date:

Related Keywords:

  • Brain Neoplasm
  • Glioma
  • Diffuse Infiltrating Pontine Glioma
  • Supratentorial High Grade Glioma
  • Convection-Enhanced Delivery
  • Pediatric Brain Tumor
  • Brain Tumor
  • Glioma
  • Brain Neoplasms
  • Neoplasms
  • Glioma



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892