Interstitial Infusion of IL13-PE38QQR Cytotoxin in Recurrent Malignant Glioma

This study has been completed.
Sponsor:
Information provided by:
INSYS Therapeutics Inc
ClinicalTrials.gov Identifier:
NCT00024570
First received: September 20, 2001
Last updated: June 2, 2011
Last verified: June 2011
  Purpose

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.

IL13-PE38QQR will be infused in two courses of 96 hours each, eight weeks apart, directly into the malignant brain tumors of patients to determine the dose of drug these patients can tolerate. After that, the selected dose will be studied to give an estimate of the response rate, response duration, time to response, and survival after infusing that dose of IL13-PE38QQR into the recurrent malignant glioma.


Condition Intervention Phase
Malignant Glioma
Glioblastoma Multiforme
Anaplastic Astrocytoma
Mixed Oligoastrocytoma
Drug: IL13-PE38QQR
Procedure: targeted fusion protein therapy
Procedure: surgery
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Interstitial Infusion of IL13-PE38QQR Cytotoxin in Recurrent Malignant Glioma: Phase I/II Study

Resource links provided by NLM:


Further study details as provided by INSYS Therapeutics Inc:

Estimated Enrollment: 60
Study Start Date: November 2000
Study Completion Date: July 2007
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

I. Determine the toxicities and maximum tolerated dose of IL13-PE38QQR delivered by continuous infusion into malignant glioma over 96 hours, in two courses eight weeks apart.

II. Estimate the response rate, response duration, time to response, and survival after interstitial infusion of IL13-PE38QQR into recurrent malignant glioma.

III. Describe the toxicities of interstitial infusion of IL13-PE38QQR at the selected dose.

PROTOCOL OUTLINE: Patients are expected to receive two IL13-PE38QQR infusions at 8-week intervals. For each course, drug will be infused through each of two catheters; infusion rate will be held constant during a 96-hour infusion.

In Phase I, the dose of IL13-PE38QQR will be increased by increasing the IL13-PE38QQR concentration in stepwise fashion, while holding infusion volume and duration constant. Three patients will be treated at each dose level until the maximum tolerated dose (MTD) is reached, and an additional three patients are treated at that level. In Phase II, patients will be treated at the selected MTD.

PROJECTED ACCRUAL: In Phase I, up to 30 patients will be treated. In Phase II, up to 35 patients will be treated.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Disease Characteristics

  • Must have had surgery (or biopsy) of a supratentorial brain tumor with pathologic diagnosis of malignant (grade 3 or 4) glioma, including anaplastic astrocytoma, glioblastoma multiforme and malignant mixed oligoastrocytoma. (Note: If diagnosis is dependent upon the Day 0 biopsy, pathology must be confirmed prior to start of IL13PE-38QQR infusion).
  • Must have received cranial radiotherapy, with tumor dose of at least 48 Gy, completed at least 12 weeks prior to study entry.
  • Must have radiographic evidence of recurrent or progressive supratentorial tumor compared with a previous study. The baseline tumor measurements must be determined within 2 weeks prior to study entry. The tumor must have a solid portion at least 1.0 cm but not more than 5.0 cm in maximum diameter. A maximum of one satellite lesion is permitted, if separated by less than 3 cm from the primary mass.
  • Stereotaxic biopsy at study entry must confirm the presence of glioma.

Patient Characteristics

  • Age 18 or greater.
  • Karnofsky Performance Score must be at least 60.
  • Hematologic status: Absolute neutrophils at least 1,500/mm^3; Hemoglobin at least 10 gm/dL; Platelets at least 100,000/mm^3; PT & PTT less than or equal to the upper limit of normal.
  • Hepatic Status: Transaminases not more than 2.5 x upper limit of normal; Total Bilirubin not more than 2.0 mg/dL.
  • Must have recovered from toxicity of prior therapy; at least 6 weeks elapsed since receiving nitrosourea-containing chemotherapy and 3 weeks since receiving any other chemotherapy.
  • Must practice an effective method of birth control during the study.
  • Must understand the investigational nature of this study and its potential risks and benefits, and must sign informed consent.
  • No patients with more than two foci of tumor, tumor crossing the midline, or leptomeningeal tumor dissemination.
  • No patients with impending herniation, spinal cord compression, or uncontrolled seizures.
  • No patients who have received any localized antitumor therapy for the malignant glioma, either intralesional chemotherapy or focal radiotherapy (i.e. any form of stereotaxic RT or brachytherapy).
  • No patients who are receiving concurrent chemotherapy or another investigational agent.
  • No patients with prior or concurrent malignancy. (Patients with curatively treated carcinoma-in-situ or basal cell skin carcinoma OR who have been free of disease for at least 5 years are eligible).
  • Female patients must not be pregnant or breast-feeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00024570

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States
United States, Florida
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Maryland
The Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, Michigan
Henry Ford Health Systems
Detroit, Michigan, United States, 48202
United States, North Carolina
Wake Forest University
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Sponsors and Collaborators
INSYS Therapeutics Inc
Investigators
Study Chair: Jon Weingart, MD The Johns Hopkins University
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00024570     History of Changes
Other Study ID Numbers: IL13PEI-001, NCI-NABTT-9903, JHU-NABTT-9903
Study First Received: September 20, 2001
Last Updated: June 2, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by INSYS Therapeutics Inc:
neurosurgery, craniotomy
convection-enhanced delivery
CNS interstitial infusion
recombinant toxins
malignant glioma, recurrent
catheter, stereotaxic
intratumoral therapy
positive pressure microinfusion

Additional relevant MeSH terms:
Glioblastoma
Glioma
Astrocytoma
Oligodendroglioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on September 30, 2014