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