Immunotoxin Therapy in Treating Children With Recurrent Malignant Gliomas

NCT ID: NCT00053040

Last Updated: 2010-09-24

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-10-31

Brief Summary

RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of immunotoxin therapy and to see how well it works in treating children undergoing surgery for recurrent or progressive malignant glioma.

Detailed Description

OBJECTIVES:

Primary

• Determine the toxicity of peritumoral IL13-PE38QQR after surgical resection in pediatric patients with recurrent malignant gliomas. (Phase I)
• Determine the maximum tolerated flow rate and maximum tolerated infusion concentration (MTiC) of this drug in these patients. (Phase I)
• Estimate the rate of survival after initial progression in patients treated at the maximum safe flow rate and MTiC with this drug. (Phase II)

Secondary

• Describe the overall safety and tolerability of this regimen in these patients from the start of infusion through disease progression or initiation of alternative treatment.
• Determine the IL13 receptor α2 chain expression status and distribution in pediatric recurrent or progressive malignant gliomas
• Estimate the progression-free survival of patients treated with this drug. (Phase II)

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

• Phase I: Patients undergo surgical resection of the tumor. Within 2-7 days later, patients undergo placement of 2-4 peritumoral catheters. One to 2 days later, patients receive peritumoral IL13-PE38QQR continuously over 96 hours. Catheters are removed after completion of the infusion.

Cohorts of 3 patients receive IL13-PE38QQR at escalating flow rates and a fixed concentration until the maximum safe flow rate is determined. The maximum safe flow rate is defined as the rate prior to the one at which 2 of 3 or more patients experience dose-limiting toxicity.

Following determination of the maximum safe flow rate, cohorts of 2-3 patients receive IL13-PE38QQR at escalating concentrations at the maximum safe flow rate until the maximum tolerated infusion concentration (MTiC) is determined. The MTiC is defined as the concentration prior to the one at which 2 of 3 or more patients experience dose-limiting toxicity.

• Phase II: Patients receive IL13-PE38QQR as above at the maximum safe flow rate and MTiC determined in the phase I of the study.

Patients are followed at week 18 after catheter placement and then every 8 weeks thereafter until death, disease progression, or completion of six months (phase I) or 12 months (phase II) of follow-up after the end of IL13-PE38QQR infusion. Phase II patients who complete one year of follow-up without disease progression are followed every 12 weeks thereafter until death.

PROJECTED ACCRUAL: Approximately 2-50 patients (2-24 for phase I and approximately 26 for phase II) will be accrued for this study.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Surgery for tumor resection + IL13-PE38QQR infusion

Group Type: EXPERIMENTAL

cintredekin besudotox

Intervention Type: BIOLOGICAL

IL13-PE38QQR is administered intracerebrally by continuous convection enhanced infusion at a starting concentration of 0.25 μg/mL. Infusion duration will be held constant at 96 hours (4 days). The phase I component of this study is to estimate the maximum safe total flow rate and the maximum safe infusion concentration.

conventional surgery

Intervention Type: PROCEDURE

Conventional surgery is used for tumor resection prior to catheter placement for IL13-PE38QQR infusion.

Interventions

cintredekin besudotox

IL13-PE38QQR is administered intracerebrally by continuous convection enhanced infusion at a starting concentration of 0.25 μg/mL. Infusion duration will be held constant at 96 hours (4 days). The phase I component of this study is to estimate the maximum safe total flow rate and the maximum safe infusion concentration.

Intervention Type: BIOLOGICAL

conventional surgery

Conventional surgery is used for tumor resection prior to catheter placement for IL13-PE38QQR infusion.

Intervention Type: PROCEDURE

Other Intervention Names

IL13-PE38QQR

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed grade 3 or 4 supratentorial malignant glioma by prior surgery or biopsy

• Anaplastic astrocytoma
• Glioblastoma multiforme
• Malignant mixed oligoastrocytoma
• Recurrent or progressive disease by radiology

• In first progression or recurrence (for patients in the phase II portion of the study only)
• Must have 1 solid primary lesion with a solid component measuring at least 1 cm in diameter
• Must have received external beam radiotherapy with tumor dose of at least 48 Gy
• Planning to undergo gross total resection of the tumor to remove all contrast-enhancing components of the tumor

• No multifocal tumor not amenable to gross tumor resection
• No contrast-enhancing tumor component crossing the midline
• No subependymal or leptomeningeal tumor dissemination
• No clinically significant increased intracranial pressure (e.g., impending herniation)
• No spinal cord compression
• No requirement for immediate palliative treatment

PATIENT CHARACTERISTICS:

Age

• 3 to 21

Performance status

• Karnofsky 60-100% (over 16 years of age)
• Lansky 60-100 (16 years of age and under)

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* NOTE: *Transfusion independent

Hepatic

• PT and PTT normal

Renal

• Creatinine normal for age

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled seizures

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 8 weeks since prior hematopoietic stem cell transplantation

Chemotherapy

• No prior intracerebral chemotherapy for malignant glioma (except polifeprosan 20 with carmustine implant)
• At least 6 months since prior polifeprosan 20 with carmustine implant
• At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas)
• At least 2 weeks since prior vincristine or noncytotoxic chemotherapy
• No concurrent chemotherapy

Endocrine therapy

• Concurrent steroids allowed

Radiotherapy

• See Disease Characteristics
• At least 8 weeks since prior radiotherapy
• No prior focal radiotherapy for malignant glioma (e.g., single-fraction stereotaxic radiotherapy or brachytherapy)

• Prior stereotactic radiosurgery boost as part of the initial fractionated external beam radiotherapy regimen allowed

Surgery

• See Disease Characteristics

Other

• Recovered from prior therapy
• No prior investigational intracerebral agents
• At least 4 weeks since prior systemic investigational agents
• No prior localized antitumor therapy for malignant glioma
• No concurrent anticoagulants or antiplatelet therapy, including, but not limited to, any of the following:

• Heparin
• Fractionated heparin
• Warfarin
• Aspirin
• Ticlopidine
• Clopidogrel
• Dipyridamole
• No other concurrent investigational agents

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Pediatric Brain Tumor Consortium

NETWORK

Sponsor Role: lead

Responsible Party

Pediatric Brain Tumor Consortium

Principal Investigators

Anuradha Banerjee, MD

Role: STUDY_CHAIR

University of California, San Francisco

Other Identifiers

PBTC-011C

Identifier Type: OTHER

Identifier Source: secondary_id

NEOPHARM-IL13PEI-151

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-5930

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000269073

Identifier Type: -

Identifier Source: org_study_id