The PRECISE Trial: Study of IL13-PE38QQR Compared to GLIADEL Wafer in Patients With Recurrent Glioblastoma Multiforme

PRECISE - Phase III Randomized Evaluation of Convection Enhanced Delivery of IL13-PE38QQR Compared to GLIADEL® Wafer With Survival Endpoint in Glioblastoma Multiforme Patients at First Recurrence

The purpose of the PRECISE trial is to determine whether overall survival duration, safety, and quality of life are improved for patients treated with IL13-PE38QQR compared to patients treated with GLIADEL® Wafer following surgical tumor removal in the treatment of first recurrence of glioblastoma multiforme.

Study Overview

• Status: Completed
• Conditions: Glioblastoma Multiforme
• Intervention / Treatment: Drug: IL13-PE38QQR; Procedure: surgery and catheter placement (2 procedures); Drug: prolifespan 20 with carmustine implant (GLIADEL® Wafer); Procedure: surgery and wafer placement (1 procedure)

Detailed Description

PRECISE is a Phase III clinical trial of experimental drug IL13-PE38QQR (Study Drug). IL13-PE38QQR is a tumor-targeting agent administered by a continuous infusion directly into the brain around the cavity where the tumor has been removed. Through previous research, this Study Drug has shown potential to control some of the recurrent malignant gliomas, such as glioblastoma multiforme (GBM), anaplastic astrocytoma, and malignant mixed oligoastrocytoma.

The Study Drug is made by combining a human protein (IL13) with a portion of a bacterial toxin protein, Pseudomonas Exotoxin (PE). The IL13 portion binds to receptors on the tumor like a "key to a lock," allowing the PE portion to enter and kill those cells. Since tumor cells preferentially bind the drug, normal (healthy) brain cells are much less likely to be damaged by the drug. The Study Drug is delivered through tubing or catheters placed directly into the area surrounding the resection cavity. These catheters will be surgically placed from 2-7 days after the tumor has been removed. A pump is then used to slowly push the drug solution through the catheters using convection-enhanced delivery (CED) over a period of 4 days.

The GLIADEL® Wafer is an anti-cancer drug that is approved by the U.S. Food and Drug Administration (FDA) and sold for the treatment of recurrent or newly diagnosed GBM. Patients receiving GLIADEL® will have wafers placed at the time of surgery to remove tumor.

Eligible patients enrolled in the PRECISE trial will be randomly assigned to receive either IL13-PE38QQR or GLIADEL® Wafer. Patients will have a 2 out of 3 chance to receive IL13-PE38QQR and 1 out of 3 chance to receive GLIADEL® Wafer.

• Study Type: Interventional
• Enrollment: 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Toronto, Canada
    • Toronto Western Hospital Division of Neurosurgery
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Calgary Health Region
    • Edmonton, Alberta, Canada, T6G 2B7
      • Walter MacKenzie Health Sciences Center
  • Manitoba
    • Winnepeg, Manitoba, Canada
      • Cancer Care Manitoba
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Center
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook and Women's College Health Sciences Centre
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute and Hospital
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Royal University Hospital
• Germany
  • Dresden, Germany
    • Techniche Universität Dresden Klinik und Poliklinik für Neurochirurgie
  • Hamburg, Germany
    • Universitätsklinikum Hamburg-Eppendorf - Klinik für Neurochirurgie
  • Heidelberg, Germany
    • Klinikum der Universität Heidelberg
  • Kiel, Germany, D-24106
    • Universitätsklinikum Schleswig-Holstein - Klinik für Neurochirurgie
  • München, Germany, D-81377
    • Ludwig-Maximilians-Universität München - Klinikum Großhadern - Neurochirurgische Klinik und Poliklinik
• Israel
  • Petach Tikva, Israel, 49103
    • Rabin Medical Center - Department of Neurosurgery
  • Tel Aviv, Israel, 64246
    • Tel Aviv Sourasky Medical Center (TASMC)
  • Tel Hashomer, Israel, 52621
    • Sheba Medical Center - Department of Neurosurgery
• Netherlands
  • Groningen, Netherlands
    • Academisch Ziekenhuis Groningen Afd. Neurochirurgie
  • Rotterdam, Netherlands
    • Erasmus University MC, Rotterdam
• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • Institute of Neurological Sciences
  • Liverpool, United Kingdom
    • The Walton Centre for Neurology & Neurosurgery
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3410
      • University of Alabama at Birmingham - Division of Neurosurgery
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope National Medical Center
    • Los Angeles, California, United States, 90033
      • Los Angeles County/USC
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center - Neurological Institute
    • Los Angeles, California, United States, 90095-1769
      • University of California - Los Angeles Neuro-Oncology Program
    • San Francisco, California, United States, 94143
      • University of California San Francisco - Dept. of Neurological Surgery
  • Colorado
    • Aurora, Colorado, United States, 80010
      • University of Colorado Hospital - Anschutz Cancer Pavillion
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine - Department of Neurosurgery
  • Florida
    • Orlando, Florida, United States, 32804
      • Florida Hospital Neuroscience Institute
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center and Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Chicago, Illinois, United States, 60611
      • Northwestern Medical Faculty Foundation, Inc. - Dept of Neurological Surgery
    • Chicago, Illinois, United States, 60612
      • CINN at Rush Unversity Medical School
    • Evanston, Illinois, United States, 60201-1782
      • Evanston Northwestern Healthcare
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • The Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health Systems
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • St. Louis, Missouri, United States, 63104
      • St. Louis University
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center Department of Neurology
    • New York, New York, United States, 10021
      • Weill Cornell Medical College - Department of Neurological Surgery
    • New York, New York, United States, 10032
      • Columbia University Medical Center - Neurological Institute
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Carolina Neurosurgery & Spine Assoc.
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences - Department of Neurosurgery
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation Department of Neurological Surgery
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Hospital of the University of Pennsylvania
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Baptist Memorial Hospital
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • University of Texas M.D. Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Huntsman Cancer Insitute
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health Systems - Department of Neurological Surgery
  • Washington
    • Seattle, Washington, United States, 98101
      • Benaroya Research Institute at Virginia Mason Medical Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Department of Neurosurgery
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must be ≥ 18 years old.
• Patients must have clinical and/or radiographic evidence of FIRST recurrence or progression of supratentorial GBM afer a previous resection or biopsy and external beam radiation therapy.
• Patients must have histopathologic documentation of GBM at initial diagnosis.
• Patients must have had previous cytoreductive surgery or biopsy for GBM.
• Patients must have received external beam radiotherapy with ≥ 45 Gy tumor dose, completed ≥ 4 weeks prior to study entry.
• Gross total resection (i.e., ≥ 95% resection of the solid, contrast-enhancing tumor component) must be planned.
• Tumor must have a solid contrast-enhancing component ≥ 1.0 cm in diameter. Baseline measurements must be obtained ≤ 2 weeks prior to study entry.

• Patients must be in adequate condition, as indicated by:

  1. Karnofsky Performance Score ≥ 70,
  2. Adequate hematologic status: i. Absolute neutrophil count (ANC) ≥ 1,500/mm3; ii. Hemoglobin ≥ 10 gm/dL; iii. Platelets ≥ 100,000/mm3; iv. PT and aPTT ≤ 1.5 x institutional upper limit
• Patients must not be receiving concurrent anti-tumor therapy and must have recovered from toxicity of prior therapy. Minimum intervals required:
• ≥ 6 weeks after receiving nitrosourea cytotoxic drug
• ≥ 4 weeks after receiving any non-nitrosourea cytotoxic drug or any systemic investigational agent
• ≥ 2 weeks after receiving any non-cytotoxic anti-tumor drug (including celecoxib or other drugs, if they are being used as anti-tumor therapies)
• Patients must be willing to practice an effective method of birth control during the study. Female patients must not be pregnant or breast-feeding.
• Patients or legal representative must understand the investigational nature of this study and sign a written informed consent form, approved by an Institutional Review Board (IRB) or an Independent Ethics Committee (IEC), prior to performance of any study-specific procedure

Exclusion Criteria:

• Patients with contrast-enhancing tumor component crossing the midline, multi-focal tumor not amenable to gross total resection, or tumor dissemination (subependymal or leptomeningeal).
• Expected communication between ventricle and resection cavity that cannot be repaired in order to safely use GLIADEL® Wafer.
• Patients with clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment.
• Patients who have received any type of stereotactic radiosurgery or brachytherapy, with the exception of the stereotactic radiosurgery boost part of the initial fractionated external beam radiation therapy.

• Patients who have received:

  1) prior treatment with IL13-PE38QQR, or, 2) GLIADEL® Wafer, or, 3) any intracerebral investigational agent

• Patients who have demonstrated a previous hypersensitivity to BCNU or any other component of the GLIADEL® Wafer.
• Patients unwilling or unable to follow protocol requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: INSYS Therapeutics Inc

Publications and helpful links

Helpful Links

• Click here for more information regarding The PRECISE Trial.

Study record dates

Study Major Dates

• Study Start: February 1, 2004
• Primary Completion (Actual): March 1, 2007
• Study Completion (Actual): March 1, 2007

Study Registration Dates

• First Submitted: February 6, 2004
• First Submitted That Met QC Criteria: February 9, 2004
• First Posted (Estimate): February 10, 2004

Study Record Updates

• Last Update Posted (Estimate): June 6, 2011
• Last Update Submitted That Met QC Criteria: June 2, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: GBM; surgery; glioblastoma multiforme; brain tumor; infusion; central nervous system; resection; brain neoplasm; convection-enhanced delivery; recurrent GBM; recurrent malignant glioma; first recurrence; GLIADEL; supratentorial GBM
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Carmustine
• Other Study ID Numbers: IL13PEI-301-R03; PRECISE Trial