Immunotoxin Therapy in Treating Children With Progressive or Recurrent Glioblastoma Multiforme or Anaplastic Astrocytoma

Xenova Biomedix

Overview

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.

Study Type

INTERVENTIONAL

Purpose

TREATMENT

Masking

NONE

Conditions

Brain and Central Nervous System Tumors

Interventions

transferrin-CRM107BIOLOGICAL

Eligibility

Sex: ALLMin age: 5 YearsMax age: 18 Years

Medical Language ↔ Plain English

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

Locations (2)

Children's Hospital of Orange County

Orange, California, United States

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States

Data from ClinicalTrials.gov

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