Immunotoxin Therapy in Treating Patients With Malignant Glioma

NCT ID: NCT00006268

Last Updated: 2013-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-10-31
• Study Completion Date: 2005-03-31

Brief 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.

Detailed 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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Primary Study Purpose: TREATMENT

Interventions

cintredekin besudotox

Intervention Type: BIOLOGICAL

isolated perfusion

Intervention Type: DRUG

conventional surgery

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

New Approaches to Brain Tumor Therapy Consortium

OTHER

Sponsor Role: lead

Principal Investigators

Jon Weingart, MD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, United States

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Tampa, Florida, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

National Institute of Neurological Disorders and Stroke

Bethesda, Maryland, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Josephine Ford Cancer Center at Henry Ford Health System

Detroit, Michigan, United States

Comprehensive Cancer Center at Wake Forest University

Winston-Salem, North Carolina, 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

Countries

United States

Other Identifiers

NABTT-9903

Identifier Type: -

Identifier Source: secondary_id

JHOC-NABTT-9903

Identifier Type: -

Identifier Source: secondary_id

NEOPHARM-TS-G1-TI4

Identifier Type: -

Identifier Source: secondary_id

NEOPHARM-IL13PEI-001-R03

Identifier Type: -

Identifier Source: secondary_id

CDR0000068211

Identifier Type: -

Identifier Source: org_study_id