• Toxicity (Phase I) [ Designated as safety issue: Yes ]
• Maximum safe flow rate (Phase I) [ Designated as safety issue: No ]
• Maximum tolerated infusion concentration (Phase I) [ Designated as safety issue: No ]
• Survival distribution post initial recurrence or progression at the maximum safe total flow rate at maximum tolerated infusion concentration (Phase II) [ Designated as safety issue: No ]

• Toxicity (Phase I)
• Maximum safe flow rate (Phase I)
• Maximum tolerated infusion concentration (Phase I)
• Survival distribution post initial recurrence or progression at the maximum safe total flow rate at maximum tolerated infusion concentration (Phase II)

• Progression-free survival (Phase II) [ Designated as safety issue: No ]
• IL13receptor α2 chain expression status and distribution [ Designated as safety issue: No ]
• Overall safety [ Designated as safety issue: Yes ]
• Tolerability [ Designated as safety issue: Yes ]

• Progression-free survival (Phase II)
• IL13receptor α2 chain expression status and distribution
• Overall safety
• Tolerability

RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of immunotoxin therapy and to see how well it works in treating children undergoing surgery for recurrent or progressive malignant glioma.

OBJECTIVES:

Primary

• Determine the toxicity of peritumoral IL13-PE38QQR after surgical resection in pediatric patients with recurrent malignant gliomas. (Phase I)
• Determine the maximum tolerated flow rate and maximum tolerated infusion concentration (MTiC) of this drug in these patients. (Phase I)
• Determine the rate of survival after initial progression in patients treated at the maximum flow rate and MTiC with this drug. (Phase II)

Secondary

• Determine the overall safety and tolerability of this regimen in these patients.
• Determine the progression-free survival of patients treated with this drug. (Phase II)

OUTLINE: This is a multicenter, dose-escalation study.

• Phase I: Patients undergo surgical resection of the tumor. Within 2-7 days later, patients undergo placement of 2-4 peritumoral catheters. One to 2 days later, patients receive peritumoral IL13-PE38QQR continuously over 96 hours. Catheters are removed after completion of the infusion.

Cohorts of 3 patients receive IL13-PE38QQR at escalating flow rates and a fixed concentration until the maximum safe flow rate is determined. The maximum safe flow rate is defined as the rate prior to the one at which 2 of 3 or more patients experience dose-limiting toxicity.

Following determination of the maximum safe flow rate, cohorts of 2-3 patients receive IL13-PE38QQR at escalating concentrations and a fixed flow rate until the maximum tolerated infusion concentration (MTiC) is determined. The MTiC is defined as the concentration prior to the one at which 2 of 3 or more patients experience dose-limiting toxicity.

• Phase II: Patients receive IL13-PE38QQR as above at the MTiC. Patients are followed at week 18 and then every 8-12 weeks thereafter.

PROJECTED ACCRUAL: Approximately 2-50 patients (2-24 for phase I and approximately 26 for phase II) will be accrued for this study.

• Biological: cintredekin besudotox
• Procedure: conventional surgery

DISEASE CHARACTERISTICS:

• Histologically confirmed grade 3 or 4 supratentorial malignant glioma by prior surgery or biopsy

  • Anaplastic astrocytoma
  • Glioblastoma multiforme
  • Malignant mixed oligoastrocytoma

• Recurrent or progressive disease by radiology

  • In first progression or recurrence (for patients in the phase II portion of the study only)
• Must have 1 solid primary lesion with a solid component measuring at least 1 cm in diameter
• Must have received external beam radiotherapy with tumor dose of at least 48 Gy

• Planning to undergo gross total resection of the tumor to remove all contrast-enhancing components of the tumor

  • No multifocal tumor not amenable to gross tumor resection
• No contrast-enhancing tumor component crossing the midline
• No subependymal or leptomeningeal tumor dissemination
• No clinically significant increased intracranial pressure (e.g., impending herniation)
• No spinal cord compression
• No requirement for immediate palliative treatment

PATIENT CHARACTERISTICS:

Age

• 3 to 21

Performance status

• Karnofsky 60-100% (over 16 years of age)
• Lansky 60-100 (16 years of age and under)

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Hemoglobin at least 10 g/dL*
• Platelet count at least 100,000/mm^3* NOTE: *Transfusion independent

Hepatic

• PT and PTT normal

Renal

• Creatinine normal for age

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled seizures

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 8 weeks since prior hematopoietic stem cell transplantation

Chemotherapy

• No prior intracerebral chemotherapy for malignant glioma (except polifeprosan 20 with carmustine implant)
• At least 6 months since prior polifeprosan 20 with carmustine implant
• At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas)
• At least 2 weeks since prior vincristine or noncytotoxic chemotherapy
• No concurrent chemotherapy

Endocrine therapy

• Concurrent steroids allowed

Radiotherapy

• See Disease Characteristics
• At least 8 weeks since prior radiotherapy

• No prior focal radiotherapy for malignant glioma (e.g., single-fraction stereotaxic radiotherapy or brachytherapy)

  • Prior stereotactic radiosurgery boost as part of the initial fractionated external beam radiotherapy regimen allowed

Surgery

• See Disease Characteristics

Other

• Recovered from prior therapy
• No prior investigational intracerebral agents
• At least 4 weeks since prior systemic investigational agents
• No prior localized antitumor therapy for malignant glioma

• No concurrent anticoagulants or antiplatelet therapy, including, but not limited to, any of the following:

  • Heparin
  • Fractionated heparin
  • Warfarin
  • Aspirin
  • Ticlopidine
  • Clopidogrel
  • Dipyridamole
• No other concurrent investigational agents