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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

Phase 1
18 Years
Not Enrolling
Glioblastoma Multiforme, Anaplastic Astrocytoma, Oligoastrocytoma

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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.

Inclusion Criteria:

- Patients must be ≥18 years old.

- Patients must have undergone a gross total resection of the solid contrast-enhancing
lesion(s) > 1.0 cm in diameter.

- Patients must be able to have catheters placed within 14 days of tumor resection
(including a planned Gross Total Resection following an initial biopsy or subtotal

- Patients must have histopathologic confirmation of malignant glioma from resection
specimen. Diagnosis must be consistent with either GBM, AA, or malignant mixed OA.

- Patients must be in adequate general condition and meet the following criteria:

- a. Karnofsky Performance Scale score ≥ 70

- b. Adequate hematologic status:

- Absolute neutrophil count ≥ 1,500/mm³

- Hemoglobin ≥ 10 gm/dL

- Platelets ≥ 100,000/mm³

- PT & aPTT within institutional limits of normal

- Female patients must not be pregnant or breast-feeding.

- Patients must practice an effective method of birth control during the study and for
60 days beyond the last day of infusion.

- Patients must understand the investigational nature of this study and its potential
risks and benefits, and sign an approved written informed consent prior to
performance of any study-specific procedure.

Exclusion Criteria:

- Patients with residual contrast-enhancing tumor crossing the midline, multifocal
tumor not amenable to gross total resection or non-parenchymal tumor dissemination
(e.g., subependymal or leptomeningeal).

- Patients with clinically significant increased ICP (e.g., impending herniation),
uncontrolled seizures or requirement for immediate palliative treatment.

- Patients who have received any prior anti-tumor treatment (other than
corticosteroids) including any investigational agents.

- Patients with any metallic prosthesis that would prevent MRI and/or MRS scanning
procedures of the brain.

- Patients unwilling or unable to follow protocol requirements.

Type of Study:


Study Design:

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


United States: Food and Drug Administration

Study ID:




Start Date:

July 2004

Completion Date:

Related Keywords:

  • Glioblastoma Multiforme
  • Anaplastic Astrocytoma
  • Oligoastrocytoma
  • brain tumor
  • malignant glioma
  • brain neoplasm
  • central nervous system
  • surgery
  • resection
  • temozolomide
  • infusion
  • glioblastoma multiforme
  • anaplastic astrocytoma
  • oligoastrocytoma
  • Temodar
  • radiation
  • convection-enhanced delivery
  • GBM
  • Astrocytoma
  • Glioblastoma
  • Glioma
  • Oligodendroglioma



Duke University Medical Center Durham, North Carolina  27710
University of Texas M.D. Anderson Cancer Center Houston, Texas  77030
University of California San Francisco - Dept. of Neurological Surgery San Francisco, California  94143
Carolina Neurosurgery & Spine Assoc. Charlotte, North Carolina  28204
Cleveland Clinic Foundation Department of Neurological Surgery Cleveland, Ohio  44195
University of Virginia Health Systems - Department of Neurological Surgery Charlottesville, Virginia  22908