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

Phase 3
Completed
Conditions
Glioblastoma Multiforme
Registration Number
NCT00076986
Lead Sponsor
INSYS Therapeutics Inc
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
300
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (60)

City of Hope National Medical Center

🇺🇸

Duarte, California, United States

University of California - Los Angeles Neuro-Oncology Program

🇺🇸

Los Angeles, California, United States

St. Louis University

🇺🇸

St. Louis, Missouri, United States

Northwestern Medical Faculty Foundation, Inc. - Dept of Neurological Surgery

🇺🇸

Chicago, Illinois, United States

Dana Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

Huntsman Cancer Insitute

🇺🇸

Salt Lake City, Utah, United States

University of California San Francisco - Dept. of Neurological Surgery

🇺🇸

San Francisco, California, United States

Emory University

🇺🇸

Atlanta, Georgia, United States

University of Chicago Medical Center

🇺🇸

Chicago, Illinois, United States

Sheba Medical Center - Department of Neurosurgery

🇮🇱

Tel Hashomer, Israel

CINN at Rush Unversity Medical School

🇺🇸

Chicago, Illinois, United States

Carolina Neurosurgery & Spine Assoc.

🇺🇸

Charlotte, North Carolina, United States

Cleveland Clinic Foundation Department of Neurological Surgery

🇺🇸

Cleveland, Ohio, United States

Universitätsklinikum Hamburg-Eppendorf - Klinik für Neurochirurgie

🇩🇪

Hamburg, Germany

University of Virginia Health Systems - Department of Neurological Surgery

🇺🇸

Charlottesville, Virginia, United States

Techniche Universität Dresden Klinik und Poliklinik für Neurochirurgie

🇩🇪

Dresden, Germany

Calgary Health Region

🇨🇦

Calgary, Alberta, Canada

Montreal Neurological Institute and Hospital

🇨🇦

Montreal, Quebec, Canada

London Regional Cancer Center

🇨🇦

London, Ontario, Canada

Toronto Western Hospital Division of Neurosurgery

🇨🇦

Toronto, Canada

Institute of Neurological Sciences

🇬🇧

Glasgow, United Kingdom

University of Alabama at Birmingham - Division of Neurosurgery

🇺🇸

Birmingham, Alabama, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

Oregon Health & Science University

🇺🇸

Portland, Oregon, United States

Klinikum der Universität Heidelberg

🇩🇪

Heidelberg, Germany

Weill Cornell Medical College - Department of Neurological Surgery

🇺🇸

New York, New York, United States

Cedars-Sinai Medical Center - Neurological Institute

🇺🇸

Los Angeles, California, United States

Los Angeles County/USC

🇺🇸

Los Angeles, California, United States

Evanston Northwestern Healthcare

🇺🇸

Evanston, Illinois, United States

Memorial Sloan Kettering Cancer Center Department of Neurology

🇺🇸

New York, New York, United States

The Johns Hopkins University

🇺🇸

Baltimore, Maryland, United States

Henry Ford Health Systems

🇺🇸

Detroit, Michigan, United States

Columbia University Medical Center - Neurological Institute

🇺🇸

New York, New York, United States

The Ohio State University Medical Center

🇺🇸

Columbus, Ohio, United States

The Hospital of the University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

Baptist Memorial Hospital

🇺🇸

Memphis, Tennessee, United States

University of Texas M.D. Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Benaroya Research Institute at Virginia Mason Medical Center

🇺🇸

Seattle, Washington, United States

West Virginia University Department of Neurosurgery

🇺🇸

Morgantown, West Virginia, United States

Walter MacKenzie Health Sciences Center

🇨🇦

Edmonton, Alberta, Canada

Sunnybrook and Women's College Health Sciences Centre

🇨🇦

Toronto, Ontario, Canada

Rabin Medical Center - Department of Neurosurgery

🇮🇱

Petach Tikva, Israel

Ludwig-Maximilians-Universität München - Klinikum Großhadern - Neurochirurgische Klinik und Poliklinik

🇩🇪

München, Germany

Tel Aviv Sourasky Medical Center (TASMC)

🇮🇱

Tel Aviv, Israel

Erasmus University MC, Rotterdam

🇳🇱

Rotterdam, Netherlands

Academisch Ziekenhuis Groningen Afd. Neurochirurgie

🇳🇱

Groningen, Netherlands

The Walton Centre for Neurology & Neurosurgery

🇬🇧

Liverpool, United Kingdom

UT Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

Cancer Care Manitoba

🇨🇦

Winnepeg, Manitoba, Canada

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

Universitätsklinikum Schleswig-Holstein - Klinik für Neurochirurgie

🇩🇪

Kiel, Germany

University of Colorado Hospital - Anschutz Cancer Pavillion

🇺🇸

Aurora, Colorado, United States

Wake Forest University Health Sciences - Department of Neurosurgery

🇺🇸

Winston-Salem, North Carolina, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

Yale University School of Medicine - Department of Neurosurgery

🇺🇸

New Haven, Connecticut, United States

Florida Hospital Neuroscience Institute

🇺🇸

Orlando, Florida, United States

H. Lee Moffitt Cancer Center and Research Institute

🇺🇸

Tampa, Florida, United States

Royal University Hospital

🇨🇦

Saskatoon, Saskatchewan, Canada

University of Wisconsin Hospital and Clinic

🇺🇸

Madison, Wisconsin, United States

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