Los Angeles,
California
90033
Purpose:
RATIONALE: IL-4(38-37)-PE38KDEL immunotoxin may locate tumor cells and kill them without
harming normal cells. This may be an effective treatment for recurrent malignant
astrocytoma.
PURPOSE: Phase I trial to study the effectiveness of IL-4(38-37)-PE38KDEL immunotoxin in
treating patients who have recurrent malignant astrocytoma.
Study summary:
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.
Criteria:
DISEASE CHARACTERISTICS: Histologically proven recurrent glioblastoma or anaplastic
astrocytoma Stereotactically accessible, enhancing mass no greater than 50 mL total volume
by MRI No significant mass effect Recent craniotomy allowed No anaplastic
oligodendroglioma No tumors of the brainstem, cerebellum, or both hemispheres No diffuse
subependymal or CSF disease If on stable or increasing dose of steroid, must have evidence
of increasing contrast enhancement by MRI or CT scan Prior external beam radiotherapy
required
PATIENT CHARACTERISTICS: Age: Over 18 Performance status: Karnofsky 60-100% Life
expectancy: Not specified Hematopoietic: Absolute neutrophil count greater than 1500/mm3
Platelet count greater than 100,000/mm3 Hemoglobin greater than 9.5 g/dL Hepatic:
Bilirubin less than 2 mg/dL AST and ALT less than 2 times upper limit of normal (ULN)
PT/PTT no greater than ULN Renal: Creatinine less than 2 mg/dL Other: Not pregnant
Negative pregnancy test Fertile patients must use effective contraception No systemic
diseases to cause unacceptable anesthetic/operative risk No active infection requiring
treatment No unexplained febrile illness
PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent blood or platelet transfusions
Chemotherapy: At least 4 weeks since prior chemotherapy Endocrine therapy: See Disease
Characteristics Radiotherapy: See Disease Characteristics At least 4 weeks since prior
radiotherapy Surgery: See Disease Characteristics Medically able to undergo surgery Other:
No other concurrent investigational agents