PRECISE - Phase III Randomized Evaluation of Convection Enhanced Delivery of IL13-PE38QQR Compared to GLIADEL® Wafer With Survival Endpoint in Glioblastoma Multiforme Patients at First Recurrence

Inclusion Criteria:

- Patients must be ≥ 18 years old.

- Patients must have clinical and/or radiographic evidence of FIRST recurrence or
progression of supratentorial GBM afer a previous resection or biopsy and external
beam radiation therapy.

- Patients must have histopathologic documentation of GBM at initial diagnosis.

- Patients must have had previous cytoreductive surgery or biopsy for GBM.

- Patients must have received external beam radiotherapy with ≥ 45 Gy tumor dose,
completed ≥ 4 weeks prior to study entry.

- Gross total resection (i.e., ≥ 95% resection of the solid, contrast-enhancing tumor
component) must be planned.

- Tumor must have a solid contrast-enhancing component ≥ 1.0 cm in diameter. Baseline
measurements must be obtained ≤ 2 weeks prior to study entry.

- Patients must be in adequate condition, as indicated by:

1. Karnofsky Performance Score ≥ 70,

2. Adequate hematologic status: i. Absolute neutrophil count (ANC) ≥ 1,500/mm3; ii.
Hemoglobin ≥ 10 gm/dL; iii. Platelets ≥ 100,000/mm3; iv. PT and aPTT ≤ 1.5 x
institutional upper limit

- Patients must not be receiving concurrent anti-tumor therapy and must have recovered
from toxicity of prior therapy. Minimum intervals required:

- ≥ 6 weeks after receiving nitrosourea cytotoxic drug

- ≥ 4 weeks after receiving any non-nitrosourea cytotoxic drug or any systemic
investigational agent

- ≥ 2 weeks after receiving any non-cytotoxic anti-tumor drug (including celecoxib or
other drugs, if they are being used as anti-tumor therapies)

- Patients must be willing to practice an effective method of birth control during the
study. Female patients must not be pregnant or breast-feeding.

- Patients or legal representative must understand the investigational nature of this
study and sign a written informed consent form, approved by an Institutional Review
Board (IRB) or an Independent Ethics Committee (IEC), prior to performance of any
study-specific procedure

Exclusion Criteria:

- Patients with contrast-enhancing tumor component crossing the midline, multi-focal
tumor not amenable to gross total resection, or tumor dissemination (subependymal or
leptomeningeal).

- Expected communication between ventricle and resection cavity that cannot be repaired
in order to safely use GLIADEL® Wafer.

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

- Patients who have received any type of stereotactic radiosurgery or brachytherapy,
with the exception of the stereotactic radiosurgery boost part of the initial
fractionated external beam radiation therapy.

- Patients who have received:

1) prior treatment with IL13-PE38QQR, or, 2) GLIADEL® Wafer, or, 3) any intracerebral
investigational agent

- Patients who have demonstrated a previous hypersensitivity to BCNU or any other
component of the GLIADEL® Wafer.

- Patients unwilling or unable to follow protocol requirements.