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

• Status: Terminated
• Trial end date: 2015-06-05
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

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

Criteria

• INCLUSION CRITERIA:

• Age less than 18 years

• Diagnosis: recurrent or progressive:

1. DIPG

2. HGG

• Patients undergoing surgical resection must have measurable/evaluable disease prior to study entry.

• Histopathologic Diagnosis

1. 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.

2. 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

1. Patients must have received at least standard doses of radiation (i.e., greater than 54 Gy).

2. Surgery/biopsy - Patients must be more than 2 weeks from any neurosurgical procedure and cleared by the Principal Investigator before undergoing CED.

3. Radiation - Patients must be more than 4 weeks from last fraction of radiation to the target site

4. 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).

5. Biologic therapy - Patients must be greater than 7 days from biologic therapy.

6. Investigational therapy - Patients must be greater than 30 days from any investigational therapy.

• Patients must be healthy enough to tolerate surgery and general anesthesia in the opinion of the primary investigator. This includes, but is not limited to:

1. Adequate baseline organ function, including an age-adjusted normal serum creatinine OR a creatinine clearance greater or equal to 60 mL/min/1.73m(2), total bilirubin less than 2 times the upper limit of normal (ULN) and direct bilirubin within normal limits. Patients with elevated SGPT (up to 5 times ULN) will be eligible if the elevation is attributed to steroid treatment.

2. If neurological deficits are present, they must be stable for at least 1 week prior to registration.

• Patients must be able to undergo MR-imaging with gadolinium-based contrast administration (e.g. no ferrous-containing implants, no pacemakers, no allergy to contrast, etc).

• All patients or their legal guardians must sign a document of informed consent indicating their understanding of the investigational nature and the potential risks associated with this study. When appropriate, pediatric patients will be included in all discussions in order to obtain verbal and written assent.

EXCLUSION CRITERIA:

• 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.