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.