immunotoxin therapy in treating patients with malignant glioma

Conditions: Brain and Central Nervous System Tumors

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.

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.

Eligibility 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

Keywords: recurrent adult brain tumor adult glioblastoma adult anaplastic astrocytoma adult mixed glioma adult giant cell glioblastoma adult gliosarcoma