A Phase I Study of a Recombinant Chimeric Protein Composed of Circularly Permuted IL-4 and a Mutated Form of the Pseudomonas Exotoxin Termed IL-4(38-37)-PE38KDEL (IL-4 Toxin) for the Treatment of Recurrent Malignant Astrocytoma
OBJECTIVES: I. Determine the maximum tolerated dose of intratumorally infused
IL-4(38-37)-PE38KDEL immunotoxin in patients with recurrent malignant astrocytoma. II.
Determine the safety of this regimen in these patients. III. Determine preliminarily any
efficacy of this regimen in these patients.
OUTLINE: This is a dose escalation, multicenter study. Patients undergo a stereotactic
biopsy under MR/CT guidance. Catheters are then placed into the tumor under stereotactic
guidance. The catheter is filled with IL-4(38-37)-PE38KDEL immunotoxin (IL-4 toxin), with
infusion beginning 24 hours after catheter insertion. The IL-4 toxin is infused over 4 days.
The catheter is removed 45 minutes after the infusion is completed and a MR scan is
performed. Cohorts of 3 patients each receive escalating doses of IL-4 toxin until the
maximum tolerated dose (MTD) is reached. The MTD is defined as the dose preceding the dose
at which 2 of 3 patients experience dose limiting toxicity. Patients are followed every 4
weeks for 16 weeks, then every 8 weeks for up to 3 years.
PROJECTED ACCRUAL: Approximately 30 patients will be accrued for this study.
Primary Purpose: Treatment
Ronald E. Warnick, MD
Barrett Cancer Center
United States: Federal Government
|Barrett Cancer Center, The University Hospital||Cincinnati, Ohio 45219|
|UCSF Cancer Center and Cancer Research Institute||San Francisco, California 94115-0128|
|St. Louis University Health Sciences Center||Saint Louis, Missouri 63110-0250|
|John Wayne Cancer Institute||Santa Monica, California 90404|
|Herbert Irving Comprehensive Cancer Center||New York, New York 10032|
|Laboratory of Molecular Biology||Bethesda, Maryland 20892|
|University of Southern California, Healthcare Consultation Center||Los Angeles, California 90033|
|Neuro-Oncology Service||San Francisco, California 94143-0372|
|Food and Drug Administration||Rockville, Maryland 20857|
|Charlotte Neurosurgical Associates||Charlotte, North Carolina 28207-1830|