IL-4(38-37)-PE38KDEL Immunotoxin in Treating Patients With Recurrent Malignant Astrocytoma

Brain and Central Nervous System Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00003842
• Other study ID #: CDR0000067001
• Secondary ID: UCMC-981061NBI-3
• Status: Active, not recruiting
• Phase: Phase 1
• First received: November 1, 1999
• Last updated: December 17, 2013
• Start date: March 1999

Study information

• Verified date: June 1999
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Astrocytoma
• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Biological:
• interleukin-4 PE38KDEL cytotoxin

Drug:
• isolated perfusion

Procedure:
• surgical procedure

Locations

Country	Name	City	State
United States	Laboratory of Molecular Biology	Bethesda	Maryland
United States	Charlotte Neurosurgical Associates	Charlotte	North Carolina
United States	Barrett Cancer Center, The University Hospital	Cincinnati	Ohio
United States	University of Southern California, Healthcare Consultation Center	Los Angeles	California
United States	Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Food and Drug Administration	Rockville	Maryland
United States	St. Louis University Health Sciences Center	Saint Louis	Missouri
United States	Neuro-Oncology Service	San Francisco	California
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	John Wayne Cancer Institute	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Barrett Cancer Center

Country where clinical trial is conducted

United States,