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

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

The purpose of the PRECISE trial is to determine whether overall survival duration, safety, and quality of life are improved for patients treated with IL13-PE38QQR compared to patients treated with GLIADEL® Wafer following surgical tumor removal in the treatment of first recurrence of glioblastoma multiforme.

PRECISE is a Phase III clinical trial of experimental drug IL13-PE38QQR (Study Drug). 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 from 2-7 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.

The GLIADEL® Wafer is an anti-cancer drug that is approved by the U.S. Food and Drug Administration (FDA) and sold for the treatment of recurrent or newly diagnosed GBM. Patients receiving GLIADEL® will have wafers placed at the time of surgery to remove tumor.

Eligible patients enrolled in the PRECISE trial will be randomly assigned to receive either IL13-PE38QQR or GLIADEL® Wafer. Patients will have a 2 out of 3 chance to receive IL13-PE38QQR and 1 out of 3 chance to receive GLIADEL® Wafer.

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.