Trial Information

Phase I Study of Convection Enhanced Delivery (CED) of IL13-PE38QQR Infusion After Resection Followed by Radiation Therapy With or Without Temozolomide in Patients With Newly Diagnosed Supratentorial Malignant Glioma

This is a Phase I clinical trial of experimental drug IL13-PE38QQR (Study Drug) in patients
with newly diagnosed malignant glioma. IL13-PE38QQR is a tumor-targeting agent administered
by a continuous infusion directly into the brain around the cavity where the tumor has been
removed. Through previous research, this Study Drug has shown potential to control some of
the recurrent malignant gliomas, such as glioblastoma multiforme (GBM), anaplastic
astrocytoma, and malignant mixed oligoastrocytoma.

The Study Drug is made by combining a human protein (IL13) with a portion of a bacterial
toxin protein, Pseudomonas Exotoxin (PE). The IL13 portion binds to receptors on the tumor
like a "key to a lock," allowing the PE portion to enter and kill those cells. Since tumor
cells preferentially bind the drug, normal (healthy) brain cells are much less likely to be
damaged by the drug.

The Study Drug is delivered through tubing or catheters placed directly into the area
surrounding the resection cavity. These catheters will be surgically placed within 14 days
after the tumor has been removed. A pump is then used to slowly push the drug solution
through the catheters using convection-enhanced delivery (CED) over a period of 4 days.

Following treatment with IL13-PE38QQR, all patients will receive standard courses of
radiation therapy. In addition, some patients will receive adjuvant temozolomide with
radiation therapy and continue with temozolomide after radiation therapy is completed.

Temozolomide is an anti-cancer drug that is approved by the U.S. Food and Drug
Administration (FDA) and sold for the treatment of recurrent GBM.

This study will determine the maximum tolerated dose of IL13-PE38QQR when administered by
CED after tumor resection and prior to radiation therapy with or without adjuvant
temozolomide. Patients with newly diagnosed malignant glioma who have had a gross total
resection of their tumor and who meet all other specified eligibility criteria may be
entered into the study.

Patients will be divided into 2 groups:

1. Stratum A - will receive treatment with IL13-PE38QQR followed by radiation therapy and

2. Stratum B - will receive treatment with IL13-PE38QQR followed by radiation therapy with
adjuvant temozolomide. Treatment with temozolomide for Stratum B will continue after
radiation therapy is completed.

Subgroups (cohorts) of patients will be treated with up to 3 doses of IL13-PE38QQR. Cohorts
of 3-6 patients will be treated at each dose level. Enrollment into each subsequent cohort
will be dependent upon the safety and tolerability of treatment in the previous cohort.

All patients will need to have histopathological confirmation of malignant glioma diagnosis
from tissue sample obtained at the time of gross total resection within 14 days of
stereotactic catheter placement. Each patient will have 2-4 standard microinfusion catheters
placed and infusion of IL13-PE38QQR will begin within 24 hours of catheter placement. The
infusion will last for 96 hours. Approximately 2 weeks after completion of infusion, imaging
for radiation therapy planning, a physical examination, and neurological and laboratory
assessments will be performed. Patients, if stable, will then receive standard fractionated
external beam radiation therapy with a total dose between 5940-6100 cGy using 180 to 200 cGy
per fraction.

For those patients assigned to receive temozolomide in combination with radiation therapy,
the dose of temozolomide will be administered on each day of radiation therapy and will be
based on the patient's body surface area BSA at a dose of 75 mg/m²/day. After radiation
therapy is completed and the follow-up MRI has revealed stable disease or a response,
patients will continue temozolomide using repeat scheduled dosing at 150 -200 mg/m²/day for
5 consecutive days per 28 day cycle. Treatment cycles will continue for up to 12 cycles.