Phase I/II Trial of Intracerebral IL13-PE38QQR Infusions in Pediatric Patients With Recurrent Malignant Glioma

November 11, 2014 updated by: INSYS Therapeutics Inc

IL13-PE38QQR is an oncology drug product consisting of IL13 (interleukin-13) and PE38QQR (a bacteria toxin). IL3-PE38QQR is a protein that exhibits cell killing activity against a variety of IL13-receptor positive tumor cell lines indicating that it may show a therapeutic benefit. In reciprocal competition experiments, the interaction between IL13-PE38QQR and the IL13 receptors was shown to be highly specific for human glioma cells.

Study Overview

Status

Withdrawn

Conditions

Recurrent Malignant Glioma

Intervention / Treatment

Drug: IL13-PE38QQR

Detailed Description

PHASE I OBJECTIVES:

I. To describe toxicities and estimate the maximum safe flow rate and maximum tolerated infusion concentration, of IL13-PE38QQR delivered after surgical resection by peritumoral infusion via 2 to 4 catheters positioned in the brain adjacent to the resection cavity, from the start of infusion through the DLT observation period.

II. To determine the IL13 receptor alpha-2 chain expression status and distribution in pediatric recurrent or progressive malignant gliomas.

III. To describe the overall safety and tolerability of IL13PE38QQR infusion from the start of infusion through disease progression or initiation of alternative treatment.

PHASE II OBJECTIVES:

I. To estimate the survival distribution post initial progression, at the maximum safe total flow rate and MTiC established in phase I.

II. To estimate the progression-free survival distribution for patients post-initial progression or recurrence at the maximum safe total flow rate and MTiC established in phase I.

III. To determine the serum levels of IL13-PE38QQR and distribution in pediatric recurrent or progressive malignant gliomas.

IV. To describe the overall safety and tolerability of IL13-PE38QQR infusion from the start of infusion through disease progression or initiation of alternative treatment.

PROTOCOL OUTLINE: At study entry, all patients will be registered prior to planned gross total resection (> 95% resection of the solid, contrast enhancing tumor component). On the day of catheter placement (CP, 2-7 days after resection), if the patient is neurologically stable, 2-4 catheters will be stereotactically placed. On day 1 after catheter placement, infusion of IL3-PE38QQR will begin if the patient is neurologically stable and will continue for 96 hours. In Phase I, the total flow rate and the concentration of IL3-PE38QQR will be determined by the dose escalation plan. In the Phase II evaluations of safety and efficacy, patients will be treated at the flow rate and concentration identified in Phase I.

PROJECTED ACCRUAL: Approximately 24 patients will participate in the Phase I portion of the study. During the Phase I portion, the rate-limiting factor is the time the study must be closed during the toxicity assessment period. Although it is estimated that 1.5 patients per month will enroll in the Phase I portion, the observed rate may be lower due to temporary suspensions in accrual. It is not possible to estimate the time required to complete the Phase I portion of the trial. It is estimated that approximately 26 patients will contribute to the Phase II portion. Using the same rough estimate of accrual, the Phase II portion may last about 3 years.

Study Type

Interventional

Phase

Phase 2
Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- California
  - San Francisco, California, United States, 94143
    - University of California San Francisco
- District of Columbia
  - Washington, District of Columbia, United States, 20010
    - Children's National Medical Center
- Illinois
  - Chicago, Illinois, United States, 60614
    - Children's Memorial Hospital
- Massachusetts
  - Boston, Massachusetts, United States, 02215
    - Dana-Farber Cancer Institute-Dept of Pediatric Oncology
- North Carolina
  - Durham, North Carolina, United States, 27710
    - Duke University Medical Center-Dept. of Pediatrics, Medicine & Surgery
- Pennsylvania
  - Philadelphia, Pennsylvania, United States, 19104
    - The Children's Hospital of Philadelphia
  - Pittsburgh, Pennsylvania, United States, 15213
    - Children's Hospital of Pittsburgh
- Tennessee
  - Memphis, Tennessee, United States, 38014
    - St. Jude Children's Research Hospital
- Texas
  - Houston, Texas, United States, 77030
    - Baylor College of Medicine-Dept of Pediatrics
- Washington
  - Seattle, Washington, United States, 98105
    - Children's Hospital & Regional Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 21 years (ADULT, CHILD)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

-Disease Characteristics-

Must be at least 3 years but not more than 21 years of age.

Must have had surgery (or biopsy) of a supratentorial brain tumor with pathologic diagnosis of malignant (grade 3 or 4) glioma, including anaplastic astrocytoma, mixed anaplastic astrocytoma, or glioblastoma multiforme.

Must have radiographic evidence of recurrent or progressive supratentorial malignant glioma compared with a prior imaging study. The baseline tumor measurements must be determined within 2 weeks prior to study entry.

The tumor must have a solid component at least 1.0 cm in diameter.

Gross total resection must be planned, with the intent of removing all contrast-enhancing components of the tumor.

Must have received external beam radiotherapy, with tumor dose of at least 48 Gy; and must be completed at least 8 weeks prior to study entry.

-Patient Characteristics-

Karnofsky Performance Score for patients older than 16 years, or the Lansky Performance Scale for patients 16 years old or younger, must be at least 60.

Hematologic status: Absolute neutrophils at least 1,500/mm3; Hemoglobin at least 10 gm/dL (transfusion independent); Platelets at least 100,000/mm3 (transfusion independent); PT & aPTT less than or equal to the institutional upper limit of normal.

Must have recovered from toxicity of prior therapy: at least 6 months after Gliadel® wafer; at least 8 weeks after hematopoietic stem cell transplant; at least 4 weeks after any cytotoxic chemotherapy or any systemic investigational agent; at least 6 weeks after nitrosoureas; at least 2 weeks after vincristine or non-cytotoxic chemotherapy.

Patient's legal guardian must understand the investigational nature of this study and its potential risks and benefits; must sign informed consent.

No pregnant or breast-feeding patients. All patients of child-bearing age, male and female, must practice an effective method of birth control during the study.

No patients with multi-focal tumor not amenable to gross total resection or tumor dissemination (subependymal or leptomeningeal).

No patients with clinically significant increased intracranial pressure (e.g., impending herniation) uncontrolled seizures, or requirement for immediate palliative treatment.

No patients who received any localized antitumor therapy for the malignant glioma, either intracerebral chemotherapy (other than Gliadel®) or focal radiation therapy (e.g., stereotactic radiosurgery or brachytherapy).

No patients who are receiving concurrent chemotherapy (other than steroids) or any other investigational agent.

No patients unwilling to follow protocol requirements.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: TREATMENT
Allocation: NON_RANDOMIZED
Interventional Model: SINGLE_GROUP
Masking: NONE

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

INSYS Therapeutics Inc

Collaborators

Pediatric Brain Tumor Consortium (PBTC), St. Jude Children's Research Hospital

Investigators

Principal Investigator: Anuradha Banerjee, MD, MPH, University of California at San Francisco

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

First Submitted

September 18, 2006

First Submitted That Met QC Criteria

September 18, 2006

First Posted (ESTIMATE)

September 19, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

November 13, 2014

Last Update Submitted That Met QC Criteria

November 11, 2014

Last Verified

November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

IL13PEI-151
NCI Protocol No.: PBTC-011

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.