Interstitial Infusion of IL13-PE38QQR Cytotoxin in Recurrent Malignant Glioma
Interstitial Infusion of IL13-PE38QQR Cytotoxin in Recurrent Malignant Glioma
IL13-PE38QQR is an oncology drug product consisting of IL13 (interleukin-13) and PE38QQR (a
 bacteria toxin). IL3-PE38QQR is a protein that exhibits cell killing activity against a
 variety of IL13 receptor-positive tumor cell lines indicating that it may show a therapeutic
 benefit. In reciprocal competition experiments, the interaction between IL13-PE38QQR and the
 IL13 receptors was shown to be highly specific for human glioma cells.

 IL13-PE38QQR will be infused in two courses of 96 hours each, eight weeks apart, directly
 into the malignant brain tumors of patients to determine the dose of drug these patients can
 tolerate. After that, the selected dose will be studied to give an estimate of the response
 rate, response duration, time to response, and survival after infusing that dose of
 IL13-PE38QQR into the recurrent malignant glioma.
OBJECTIVES:

 I. Determine the toxicities and maximum tolerated dose of IL13-PE38QQR delivered by
 continuous infusion into malignant glioma over 96 hours, in two courses eight weeks apart.

 II. Estimate the response rate, response duration, time to response, and survival after
 interstitial infusion of IL13-PE38QQR into recurrent malignant glioma.

 III. Describe the toxicities of interstitial infusion of IL13-PE38QQR at the selected dose.

 PROTOCOL OUTLINE: Patients are expected to receive two IL13-PE38QQR infusions at 8-week
 intervals. For each course, drug will be infused through each of two catheters; infusion rate
 will be held constant during a 96-hour infusion.

 In Phase I, the dose of IL13-PE38QQR will be increased by increasing the IL13-PE38QQR
 concentration in stepwise fashion, while holding infusion volume and duration constant. Three
 patients will be treated at each dose level until the maximum tolerated dose (MTD) is
 reached, and an additional three patients are treated at that level. In Phase II, patients
 will be treated at the selected MTD.

 PROJECTED ACCRUAL: In Phase I, up to 30 patients will be treated. In Phase II, up to 35
 patients will be treated.
Disease Characteristics

 -  Must have had surgery (or biopsy) of a supratentorial brain tumor with pathologic
 diagnosis of malignant (grade 3 or 4) glioma, including anaplastic astrocytoma,
 glioblastoma multiforme and malignant mixed oligoastrocytoma. (Note: If diagnosis is
 dependent upon the Day 0 biopsy, pathology must be confirmed prior to start of
 IL13PE-38QQR infusion).

 -  Must have received cranial radiotherapy, with tumor dose of at least 48 Gy, completed
 at least 12 weeks prior to study entry.

 -  Must have radiographic evidence of recurrent or progressive supratentorial tumor
 compared with a previous study. The baseline tumor measurements must be determined
 within 2 weeks prior to study entry. The tumor must have a solid portion at least 1.0
 cm but not more than 5.0 cm in maximum diameter. A maximum of one satellite lesion is
 permitted, if separated by less than 3 cm from the primary mass.

 -  Stereotaxic biopsy at study entry must confirm the presence of glioma.

 Patient Characteristics

 -  Age 18 or greater.

 -  Karnofsky Performance Score must be at least 60.

 -  Hematologic status: Absolute neutrophils at least 1,500/mm^3; Hemoglobin at least 10
 gm/dL; Platelets at least 100,000/mm^3; PT & PTT less than or equal to the upper limit
 of normal.

 -  Hepatic Status: Transaminases not more than 2.5 x upper limit of normal; Total
 Bilirubin not more than 2.0 mg/dL.

 -  Must have recovered from toxicity of prior therapy; at least 6 weeks elapsed since
 receiving nitrosourea-containing chemotherapy and 3 weeks since receiving any other
 chemotherapy.

 -  Must practice an effective method of birth control during the study.

 -  Must understand the investigational nature of this study and its potential risks and
 benefits, and must sign informed consent.

 -  No patients with more than two foci of tumor, tumor crossing the midline, or
 leptomeningeal tumor dissemination.

 -  No patients with impending herniation, spinal cord compression, or uncontrolled
 seizures.

 -  No patients who have received any localized antitumor therapy for the malignant
 glioma, either intralesional chemotherapy or focal radiotherapy (i.e. any form of
 stereotaxic RT or brachytherapy).

 -  No patients who are receiving concurrent chemotherapy or another investigational
 agent.

 -  No patients with prior or concurrent malignancy. (Patients with curatively treated
 carcinoma-in-situ or basal cell skin carcinoma OR who have been free of disease for at
 least 5 years are eligible).

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