• Survival at 1 year [ Designated as safety issue: No ]
  

• Progression-free survival at 1 year [ Designated as safety issue: No ]
  
• Response as measured by radiographic criteria [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the maximum safe volume rate and maximum tolerated infusion concentration of TGFa-PE38 toxin (TP-38) infused through 2 or 3 catheters in pediatric patients with recurrent or progressive supratentorial high-grade glioma.
• Determine the toxic effects of this drug in these patients.
• Determine the efficacy of this drug, in terms of post-infusion survival, in these patients.

Secondary

• Determine the prevalence of epidermal growth factor receptor (EGFR) expression and phosphorylation (activity) in patients treated with this drug.
• Correlate EGFR expression with qualitative measures (e.g., histology, grade, and other tumor characteristics) and tumor response, survival, and progression-free survival in patients treated with this drug.
• Determine the objective response rate in patients treated with this drug.
• Determine the progression-free survival of patients treated with this drug.

OUTLINE: This is a dose-escalation, multicenter study. Patients in the phase I portion of the study are stratified according to the number of successfully placed catheters (3 catheters vs 2 catheters). Patients in the phase II portion of the study are stratified according to time of recurrence of high-grade glioma (first vs second or greater) and disease progression (yes or no).

• Phase I: Patients undergo stereotactic biopsy or resection of the tumor followed by intratumoral (or tumor bed) catheter placement for treatment infusion. Within 12-48 hours after intratumoral (or tumor bed) catheter placement, patients receive TGFa-PE38 toxin (TP-38) intratumorally through 2 or 3 catheters over 33 to 124 hours. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients (in each stratum) receive escalating volumes followed by escalating concentrations of TP-38 until the maximum safe volume (MSV) and maximum tolerated infusion concentration (MTIC) are determined. The MSV and MTIC are defined as the volume and concentration preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

• Phase II: Patients receive treatment as in phase I at the MSV and MTIC. Patients are followed at 30 days, every 3 months for 1 year, and then every 6 months for at least 2 years.

PROJECTED ACCRUAL: A total of 6-105 patients (6-60 for phase I and 45 for phase II) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed supratentorial malignant glioma

  • Recurrent or progressive disease
• Amenable to gross total resection, clinically indicated partial resection, or biopsy

• Tumor must have a single solid portion at least 1 cm and no greater than 5 cm in maximum diameter

  • No tumor crossing midline

    • Tumors invading the corpus callosum that do not extend beyond to midline or into the contralateral hemisphere allowed
  • No more than 1 focus of tumor
  • No tumors involving the brainstem or cerebellum
  • No tumor dissemination (i.e., subependymal or leptomeningeal)
• Must be on steroids ≥ 3 days prior to surgery
• Must have received prior external beam radiotherapy (tumor dose at least 45 Gy) and completed therapy at least 8 weeks before study entry
• No impending herniation, including midline shift greater than 0.5 cm
• No requirement for immediate palliative treatment

PATIENT CHARACTERISTICS:

Age

• 3 to 21

Performance status

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

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3*
• Hemoglobin at least 9 g/dL* NOTE: *Transfusion independent

Hepatic

• ALT and AST less than 2.5 times upper limit of normal (ULN)
• PT and PTT no greater than ULN

Renal

• Creatinine less than 1.5 times normal OR
• Glomerular filtration rate greater than 70 mL/min

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 30 days after study participation
• No uncontrolled seizures
• No active infection requiring treatment
• No unexplained febrile illness
• No known or suspected allergies to local anesthetics
• No systemic disease or other condition that may be associated with unacceptable anesthetic/operative risk and/or that would preclude study completion
• No other malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 8 weeks since prior hematopoietic stem cell transplantation

Chemotherapy

• At least 6 months since prior polifeprosan 20 with carmustine implant (Gliadel® wafer)
• At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas and 2 weeks for vincristine)
• At least 2 weeks since prior non-cytotoxic chemotherapy
• No other prior intracerebral chemotherapy
• No concurrent chemotherapy

Endocrine therapy

• Concurrent steroids allowed

Radiotherapy

• See Disease Characteristics
• No prior focal radiotherapy (e.g., gamma knife radiosurgery, stereotactic radiosurgery, or brachytherapy)
• No concurrent radiotherapy

Surgery

• Not specified

Other

• Recovered from prior therapy
• At least 4 weeks since prior anticancer investigational agents
• No prior localized antitumor therapy for malignant glioma
• No other concurrent investigational agent
• No other concurrent anticancer (including alternative anticancer medicines/treatment) agent or therapy