Brain and Central Nervous System Tumors
Conditions
Keywords
recurrent adult brain tumor, adult glioblastoma, adult anaplastic astrocytoma, adult mixed glioma, adult giant cell glioblastoma, adult gliosarcoma
Brief summary
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
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.
Interventions
Sponsors
National Cancer Institute (NCI)
New Approaches to Brain Tumor Therapy Consortium
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Countries
United States
Outcome results
None listed