Immunotoxin Therapy in Treating Patients With Malignant Glioma

Study Overview
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Brief Summary
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RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells. This may be an effective treatment for malignant glioma. PURPOSE: Phase I/II trial to study the effectiveness of immunotoxin therapy in treating patients who have malignant glioma.

Detailed Description
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OBJECTIVES: Determine the toxic effects and maximum tolerated dose (MTD) of interstitial interleukin-13 PE38QQR immunotoxin in patients with malignant glioma. Determine the response rate, duration of response, time to response, overall survival, and time to progression in patients treated with this regimen. Determine the toxic effects of this drug at the MTD in these patients. OUTLINE: This is a dose-escalation, multicenter study. Patients undergo stereotactic biopsy of brain tumor followed by CT guided stereotactic placement of 2 intratumoral catheters on day 0. Patients with histologically confirmed malignant glioma receive interleukin-13 PE38QQR immunotoxin interstitially over 96 hours beginning on day 1. Patients with a residual enhancing mass undergo repeat catheter placement on day 56 and then receive a second interstitial infusion beginning on day 57 in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of interleukin-13 PE38QQR immunotoxin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting toxicity. Additional patients are treated at the MTD. Patients are followed every 8 weeks. PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for phase I of the study within 6 months and a total of 12-35 patients will be accrued for phase II of the study within 10-12 months.

Official Title
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Interstitial Infusion of IL 13-PE38QQR Cytotoxin in Recurrent Malignant Glioma: Phase I/II Study

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Biological: cintredekin besudotox
* Drug: isolated perfusion
* Procedure: conventional surgery


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven malignant glioma (grade 3 or 4) Anaplastic astrocytoma Glioblastoma multiforme Malignant mixed oligoastrocytoma Must have undergone cranial radiotherapy with tumor dose of at least 48 Gy and at least 12 weeks prior to study Must have undergone supratentorial brain tumor surgery or biopsy Must have radiographic evidence of recurrent or progressive supratentorial tumor compared with prior study Must have solid portion measuring 1.0-5.0 cm in maximum diameter Maximum of 1 satellite lesion allowed if separated from the primary mass by less than 3 cm No tumor crossing the midline No leptomeningeal tumor dissemination No impending herniation or spinal cord compression No uncontrolled seizures PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% 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 Hepatic: PT and PTT no greater than upper limit of normal (ULN) SGOT and SGPT no greater than 2.5 times ULN Bilirubin no greater than 2.0 mg/dL Renal: Not specified Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior intralesional chemotherapy for malignant glioma At least 3 weeks since other prior chemotherapy (6 weeks since prior nitrosoureas) and recovered No concurrent chemotherapy Endocrine therapy: Concurrent corticosteroids allowed, but dose must remain stable or be tapered during study Radiotherapy: See Disease Characteristics No prior focal radiotherapy (e.g., any form of stereotactic radiotherapy or brachytherapy) for malignant glioma Surgery: See Disease Characteristics Other: Recovered from any prior therapy No other concurrent investigational agent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: cintredekin besudotox|nan|
|Drug: isolated perfusion|nan|
|Procedure: conventional surgery|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult brain tumor, adult glioblastoma, adult anaplastic astrocytoma, adult mixed glioma, adult giant cell glioblastoma, adult gliosarcoma