immunotoxin therapy in treating children with progressive or recurrent glioblastoma multiforme or anaplastic astrocytoma

Conditions: Brain and Central Nervous System Tumors

Summary: rationale: immunotoxins can locate tumor cells and kill them without harming normal cells. immunotoxin therapy may be an effective treatment for glioblastoma multiforme and anaplastic astrocytoma. purpose: phase i trial to study the effectiveness of immunotoxin therapy in treating children who have progressive or recurrent glioblastoma multiforme or anaplastic astrocytoma

objectives: * determine the maximum tolerated dose of intratumoral transferrin-crm107 in pediatric patients with progressive or recurrent glioblastoma multiforme or anaplastic astrocytoma. * determine the safety of this drug in these patients. * determine the efficacy of this drug in these patients. * compare the efficacy of this drug in patients with different histological types of tumor, degrees of transferrin receptor expression, and serum antidiphtheria antibody titer levels. outline: this is a dose-escalation, open-label, multicenter study. patients are assigned to 1 of 2 treatment groups by age (5-9 vs 10-18). all patients undergo stereotactic radiosurgery for tumor biopsy and placement of 2 intratumoral silastic infusion catheters pre-loaded with transferrin-crm107 (tf-crm107). * group 1 (ages 5-9): patients receive intratumoral tf-crm107 over 3-7 days via catheter. treatment repeats after 6-10 weeks in the absence of unacceptable toxicity. three cohorts of 3-6 patients receive escalating doses of tf-crm107 until the maximum tolerated dose (mtd) is determined. * group 2 (ages 10-18): patients receive intratumoral tf-crm107 as in group 1. two cohorts of 3-6 patients receive escalating doses of tf-crm107 until the mtd is determined. the mtd in both groups is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. patients are followed monthly for 6 months and then every 3 months for 6 months. projected accrual: a total of 3-30 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed glioblastoma multiforme or anaplastic astrocytoma with the following tumor characteristics: * unifocal * unilateral and supratentorial * diameter no greater than 3.5 cm by contrast-enhanced mri * no more than 1 satellite tumor * recurrent or progressive disease * progressive disease defined as at least 25% increase in tumor volume by serial mri or ct scans and/or at least 15% increase in the largest cross-sectional area of tumor as defined by the area of contrast agent enhancement * must have received prior conventional treatment comprising both of the following: * surgery (biopsy or debulking) * radiation therapy * no evidence of mass effect on ct scan or mri with more than a 5 mm midline shift and/or nausea, vomiting, reduced level of consciousness, or clinically significant papilledema patient characteristics: age * 5 to 18 performance status * karnofsky 60-100% or * lansky play 50-100% life expectancy * at least 3 months hematopoietic * platelet count at least 100,000/mm\^3 * absolute neutrophil count at least 1,000/mm\^3 hepatic * bilirubin no greater than 2.0 mg/dl * ast and alt no greater than 2.5 times the upper limit of normal (uln) * pt or aptt no greater than 1.5 times uln renal * not specified other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for at least 2 months after study * no acute viral, bacterial, or fungal infection requiring therapy * topical treatment for oral candidiasis allowed * no other concurrent medical condition that would preclude anesthesia prior concurrent therapy: biologic therapy * no prior transferrin-crm107 chemotherapy * more than 1 month since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) * more than 3 months since prior biodegradable polymer wafers * no concurrent chemotherapy endocrine therapy * must be on stable dose of steroids for 7 days prior to infusion radiotherapy * see disease characteristics * more than 3 months since prior radiotherapy * more than 3 months since prior stereotactic radiosurgery * more than 6 weeks since prior craniospinal irradiation * no prior brachytherapy * no concurrent radiotherapy surgery * see disease characteristics * more than 1 month since prior surgery including tumor surgery or debulking * no other concurrent surgery other * more than 30 days since prior investigational agents * no other concurrent investigational therapy * no other concurrent anti-cancer drugs

Keywords: recurrent childhood cerebral astrocytoma