An Open Label Dose Escalation Safety Study of Convection-Enhanced Delivery of IL13-PE38QQR in Patients With Progressive Pediatric Diffuse Infiltrating Brainstem Glioma and Supratentorial High-grade Glioma

NCT00880061 | Terminated Phase 1

• 2 other identifiers: 09011709-N-0117
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Diffusely infiltrating pontine glioma (DIPG) or supratentorial high-grade glioma (HGG) are brain tumors that are often difficult to treat. It is very difficult to get chemotherapy agents to tumors in the brain, and researchers are looking for new methods to directly treat these types of cancer.
• IL-13 is an immune molecule normally occurring in the body. Patients with gliomas appear to have significant amounts of the IL-13 receptors in their brain tumors. An experimental drug, IL13-PE38QQR, combines a bacteria toxin with human IL-13 to allow the toxin to enter and destroy the tumor cell. Early clinical studies suggest this treatment may prolong survival of patients with these types of brain tumors.
• A technique called convection-enhanced delivery (CED) uses continuous pressure to push large molecules through the membranes protecting the brain to reach brain tumors. This technique can treat a tumor more directly than with traditional methods. Objectives:
• To test the safety and feasibility of giving IL13-PE38QQR directly into regions of the brain in pediatric patients with DIPG or HGG, using CED.
• To determine the most appropriate dose of IL13-PE38QQR to treat DIPG or HGG.
• To determine the effects of this experimental therapy on the tumor.
• To evaluate the physical changes in the tumor before and after the therapy. Eligibility:
• Patients who are less than 18 years of age and have been diagnosed with either DIPG or with supratentorial HGG that has not responded well to standard treatments. Design:
• Patients will be admitted to the hospital and will receive a magnetic resonance imaging (MRI) scan to show the exact location of the tumor. A small plastic tube will be inserted surgically into the tumor area, and IL13-PE38QQR and a MRI contrast agent (gadolinium DTPA) will be infused into the area.
• MRI scans will monitor the process, and the tube will be removed after surgery.
• Doses will be adjusted over the course of the study.
• Patients who respond well to treatment may be eligible to receive a second infusion, no sooner than 4 weeks after the first treatment.
• Post-treatment visits: Clinic visits 4 and 8 weeks after the treatment, and then every 8 weeks for up to 1 year.
• Physical examination with neurological testing, an MRI, and standard blood and urine tests.

Conditions

Brain Neoplasm; Glioma

Keywords

Diffuse Infiltrating Pontine Glioma; Supratentorial High Grade Glioma; Convection-Enhanced Delivery; Pediatric Brain Tumor; Brain Tumor; Glioma

Outcome Measures

Primary Outcomes (1)

• 1) Feasibility of perfusing specific sites within the CNS with IL13-PE38QQR, administered concurrently with gd-DTPA, 2) Safety and tolerability of escalating doses of IL13-PE38QQR via CED to pediatric patient with DIPGs and HGGs

Secondary Outcomes (1)

• Determine effect of IL13-PE38QQR on MRI tumor measurements, symptom improvement or worsening, changes on clinical exam, radiographic changes, steroid dosing, QOL testing and survival of pediatric patients with DIPG and recurrent HGG

Interventions

IL13-PE38QQR DRUG

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age less than 18 years
• Diagnosis: recurrent or progressive:
• DIPG
• HGG
• Patients undergoing surgical resection must have measurable/evaluable disease prior to study entry.
• Histopathologic Diagnosis
• A histopathologic diagnosis is not required for patients with DIPG but a biopsy may be recommended if the patient has an atypical presentation or atypical findings on MR-imaging.
• Histopathologic confirmation for patients with HGG is required. If necrosis is suspected based on MR-imaging and Nuclear Medicine scans, biopsy or surgical resection for confirmation of disease progression may be required.
• Prior Therapy
• Patients must have received at least standard doses of radiation (i.e., greater than 54 Gy).
• Surgery/biopsy - Patients must be more than 2 weeks from any neurosurgical procedure and cleared by the Principal Investigator before undergoing CED.
• Radiation - Patients must be more than 4 weeks from last fraction of radiation to the target site
• Chemotherapy - Patients must not be on concurrent chemotherapy. The last dose of chemotherapy must be greater than 2 weeks prior to CED and the patient must have recovered from any toxic effects of prior therapy (to less than Grade 2 or baseline).
• Biologic therapy - Patients must be greater than 7 days from biologic therapy.
• Investigational therapy - Patients must be greater than 30 days from any investigational therapy.

You may not qualify if:

• Patients with an uncorrectable bleeding disorder
• Patients with multifocal or leptomeningeal disease
• Patients with signs of impending herniation or an acute intratumoral hemorrhage
• Patients on concurrent chemotherapy or biologic therapy for the treatment of their tumor
• Patients who are pregnant or breastfeeding, because of unknown effects of the study agent, the strong magnetic fields and Gadolinium containing contrast agents on the fetus; patients of child-bearing potential must be willing to practice an effective form of birth control, including abstinence, hormone therapy, intrauterine device, 2 barrier methods.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Linabery AM, Ross JA. Trends in childhood cancer incidence in the U.S. (1992-2004). Cancer. 2008 Jan 15;112(2):416-32. doi: 10.1002/cncr.23169.

  PMID: 18074355 BACKGROUND

• Packer RJ, Sutton LN, Goldwein JW, Perilongo G, Bunin G, Ryan J, Cohen BH, D'Angio G, Kramer ED, Zimmerman RA, et al. Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma. J Neurosurg. 1991 Mar;74(3):433-40. doi: 10.3171/jns.1991.74.3.0433.

  PMID: 1847194 BACKGROUND

• Broniscer A, Gajjar A. Supratentorial high-grade astrocytoma and diffuse brainstem glioma: two challenges for the pediatric oncologist. Oncologist. 2004;9(2):197-206. doi: 10.1634/theoncologist.9-2-197.

  PMID: 15047924 BACKGROUND

• Robison NJ, Kieran MW. Diffuse intrinsic pontine glioma: a reassessment. J Neurooncol. 2014 Aug;119(1):7-15. doi: 10.1007/s11060-014-1448-8. Epub 2014 May 3.

  PMID: 24792486 DERIVED

• Chittiboina P, Heiss JD, Warren KE, Lonser RR. Magnetic resonance imaging properties of convective delivery in diffuse intrinsic pontine gliomas. J Neurosurg Pediatr. 2014 Mar;13(3):276-82. doi: 10.3171/2013.11.PEDS136. Epub 2014 Jan 10.

  PMID: 24410126 DERIVED

MeSH Terms

Conditions

Brain Neoplasms; Glioma

Interventions

IL13-PE38

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• John D Heiss, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2009
• First Posted: April 13, 2009
• Study Start: April 7, 2009
• Primary Completion: June 5, 2015
• Study Completion: June 5, 2015
• Last Updated: July 5, 2018

Record last verified: 2015-06-05

Locations

US (1)