The PRECISE Trial: Study of IL13-PE38QQR Compared to GLIADEL Wafer in Patients With Recurrent Glioblastoma Multiforme

Inclusion Criteria:

• Patients must be ≥ 18 years old.

• Patients must have clinical and/or radiographic evidence of FIRST recurrence orprogression of supratentorial GBM afer a previous resection or biopsy and externalbeam 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 tumorcomponent) must be planned.

• Tumor must have a solid contrast-enhancing component ≥ 1.0 cm in diameter. Baselinemeasurements 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 xinstitutional upper limit

• Patients must not be receiving concurrent anti-tumor therapy and must have recoveredfrom 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 systemicinvestigational agent

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

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

• Patients or legal representative must understand the investigational nature of thisstudy and sign a written informed consent form, approved by an Institutional ReviewBoard (IRB) or an Independent Ethics Committee (IEC), prior to performance of anystudy-specific procedure

Exclusion Criteria:

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

• Expected communication between ventricle and resection cavity that cannot be repairedin order to safely use GLIADEL® Wafer.

• Patients with clinically significant increased intracranial pressure (e.g., impendingherniation), 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 initialfractionated external beam radiation therapy.

• Patients who have received:

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

• Patients who have demonstrated a previous hypersensitivity to BCNU or any othercomponent of the GLIADEL® Wafer.

• Patients unwilling or unable to follow protocol requirements.