Pre-operative IL13-PE38QQR in Patients With Recurrent or Progressive Malignant Glioma

• Status: Completed
• Trial end date: 2007-07-01
• Target enrollment: 0
• Participant gender: All

Summary

IL13-PE38QQR is an oncology drug product consisting of IL13 (interleukin-13) and PE38QQR (a bacteria toxin). IL13-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.

Prior to treatment, patients will have physical and neurologic exams, MRI to measure the extent of tumor, tumor biopsy, and screening laboratory tests. On Day 1, one or two catheters will be inserted directly into the tumor, after which a CT scan will be used to confirm placement. Each patient will receive one IL13-PE38QQR infusion, and the tumor will be surgically removed on approximately Day 15. In the first group of patients, IL13-PE38QQR will be infused directly into the tumor for 4 days. Depending on effectiveness or side effects of the study drug, the duration will be increased stepwise to a maximum of 7 days in subsequent groups of patients. Once duration of infusion has been determined, the dose of IL13-PE38QQR will be increased stepwise (in separate groups of patients), depending on effectiveness or side effects of the study drug. The activity of the drug against the tumor cells will be judged by examining the removed tumor tissue. Patients will have neurologic exams and MRI scans immediately after the resection and every eight weeks until disease progression is observed.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: INSYS Therapeutics Inc

Criteria

-Disease Characteristics-

Must have prior histologic diagnosis of supratentorial malignant glioma (Grade 3 or 4), including glioblastoma multiforme, anaplastic astrocytoma, or malignant mixed oligoastrocytoma (excludes glioma of unknown grade or pure oligodendroglioma). Patients with clinical/radiographic diagnosis of malignant glioma may be registered pending histologic confirmation.

Must have undergone prior surgical resection and received external beam radiotherapy with at least 48 Gy tumor dose, completed at least 8 weeks prior to study.

Must have recurrent or progressive supratentorial tumor compared with a previous study. Baseline tumor measurements must be determined within 2 weeks prior to study. Stereotaxic biopsy at study entry must confirm the presence of glioma (malignant, unless previously known). Recurrent or progressive tumor must have a solid enhancing region at least 1.0 cm and not more than 6.0 cm in maximum diameter. (One satellite lesion is permitted, if separated by 3 cm or less from the primary mass.)

-Patient Characteristics-

Age 18 or greater.

Karnofsky Performance Score must be at least 70.

Hematologic status: Absolute neutrophils at least 1,500/mm^3; Hemoglobin at least 9 gm/dL; Platelets at least 75,000/mm^3; PT & PTT within institutional limit of normal.

Must be candidate for re-operation.

Must have recovered from toxicity of prior therapy: at least 6 months after approved intratumoral chemotherapy (e.g. carmustine wafer); at least 6 weeks after nitrosourea-containing chemotherapy; at least 4 weeks after any investigational agent or any other cytotoxic chemotherapy; at least 2 weeks after vincristine or non-cytotoxic 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 sign an approved written informed consent prior to treatment.

No patients with tumor crossing the midline (tumor involving corpus callosum is permitted if not crossing midline), more than two foci of tumor, or non-parenchymal tumor dissemination (e.g. subependymal or leptomeningeal).

No patients with impending herniation (e.g. midline shift >1 cm), spinal cord compression, uncontrolled seizures or requirement for immediate palliative treatment.

No patients who have received localized therapy for glioma, e.g. focal single-fraction radiotherapy, brachytherapy, or intracerebral infusional chemotherapy.

No patients who are receiving any concurrent chemotherapy or any other investigational agent (corticiosteroids are permitted).

Female patients must not be pregnant or breast-feeding.

No patients unwilling or unable to follow protocol requirements.