Immunotoxin Therapy in Treating Patients With Malignant Glioma

Brain and Central Nervous System Tumors Clinical Trial

Official title:

Interstitial Infusion of IL 13-PE38QQR Cytotoxin in Recurrent Malignant Glioma: Phase I/II Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006268
• Other study ID #: CDR0000068211
• Secondary ID: NABTT-9903JHOC-N
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 11, 2000
• Last updated: June 20, 2013
• Start date: October 2000
• Est. completion date: March 2005

Study information

• Verified date: March 2005
• 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: Immunotoxins can locate tumor cells and kill them without harming normal cells. This may be an effective treatment for malignant glioma.

PURPOSE: Phase I/II trial to study the effectiveness of immunotoxin therapy in treating patients who have malignant glioma.

Description:

OBJECTIVES:

• Determine the toxic effects and maximum tolerated dose (MTD) of interstitial interleukin-13 PE38QQR immunotoxin in patients with malignant glioma.

• Determine the response rate, duration of response, time to response, overall survival, and time to progression in patients treated with this regimen.

• Determine the toxic effects of this drug at the MTD in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Patients undergo stereotactic biopsy of brain tumor followed by CT guided stereotactic placement of 2 intratumoral catheters on day 0. Patients with histologically confirmed malignant glioma receive interleukin-13 PE38QQR immunotoxin interstitially over 96 hours beginning on day 1. Patients with a residual enhancing mass undergo repeat catheter placement on day 56 and then receive a second interstitial infusion beginning on day 57 in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of interleukin-13 PE38QQR immunotoxin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting toxicity. Additional patients are treated at the MTD.

Patients are followed every 8 weeks.

PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for phase I of the study within 6 months and a total of 12-35 patients will be accrued for phase II of the study within 10-12 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: March 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically proven malignant glioma (grade 3 or 4)

• Anaplastic astrocytoma

• Glioblastoma multiforme

• Malignant mixed oligoastrocytoma

• Must have undergone cranial radiotherapy with tumor dose of at least 48 Gy and at least 12 weeks prior to study

• Must have undergone supratentorial brain tumor surgery or biopsy

• Must have radiographic evidence of recurrent or progressive supratentorial tumor compared with prior study

• Must have solid portion measuring 1.0-5.0 cm in maximum diameter

• Maximum of 1 satellite lesion allowed if separated from the primary mass by less than 3 cm

• No tumor crossing the midline

• No leptomeningeal tumor dissemination

• No impending herniation or spinal cord compression

• No uncontrolled seizures

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3

• Hemoglobin at least 10 g/dL

• Platelet count at least 100,000/mm^3

Hepatic:

• PT and PTT no greater than upper limit of normal (ULN)

• SGOT and SGPT no greater than 2.5 times ULN

• Bilirubin no greater than 2.0 mg/dL

Renal:

• Not specified

Other:

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior intralesional chemotherapy for malignant glioma

• At least 3 weeks since other prior chemotherapy (6 weeks since prior nitrosoureas) and recovered

• No concurrent chemotherapy

Endocrine therapy:

• Concurrent corticosteroids allowed, but dose must remain stable or be tapered during study

Radiotherapy:

• See Disease Characteristics

• No prior focal radiotherapy (e.g., any form of stereotactic radiotherapy or brachytherapy) for malignant glioma

Surgery:

• See Disease Characteristics

Other:

• Recovered from any prior therapy

• No other concurrent investigational agent

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Biological:
• cintredekin besudotox

Drug:
• isolated perfusion

Procedure:
• conventional surgery

Locations

Country	Name	City	State
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	National Institute of Neurological Disorders and Stroke	Bethesda	Maryland
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Josephine Ford Cancer Center at Henry Ford Health System	Detroit	Michigan
United States	Abramson Cancer Center at the University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
New Approaches to Brain Tumor Therapy Consortium	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,