Clinical trial NCT00076986: The PRECISE Trial: Study of IL13-PE38QQR Compared to GLIADEL Wafer in Patients With Recurrent Glioblastoma Multiforme
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Glioblastoma Multiforme
Keywords: brain tumor
recurrent malignant glioma
brain neoplasm
central nervous system
surgery
resection
GLIADEL
infusion
glioblastoma multiforme
convection-enhanced delivery
first recurrence
recurrent GBM
GBM
supratentorial GBM
Lead sponsor: INSYS Therapeutics Inc
Sponsor class: INDUSTRY
First posted: 2004-02-10
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham - Division of Neurosurgery
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: Los Angeles County/USC
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center - Neurological Institute
state: California
city: Los Angeles
country: United States
facility: University of California - Los Angeles Neuro-Oncology Program
state: California
city: San Francisco
country: United States
facility: University of California San Francisco - Dept. of Neurological Surgery
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavillion
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine - Department of Neurosurgery
state: Connecticut
city: Orlando
country: United States
facility: Florida Hospital Neuroscience Institute
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern Medical Faculty Foundation, Inc. - Dept of Neurological Surgery
state: Illinois
city: Chicago
country: United States
facility: CINN at Rush Unversity Medical School
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Evanston
country: United States
facility: Evanston Northwestern Healthcare
state: Illinois
city: Baltimore
country: United States
facility: The Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health Systems
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: St. Louis
country: United States
facility: St. Louis University
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Department of Neurology
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College - Department of Neurological Surgery
state: New York
city: New York
country: United States
facility: Columbia University Medical Center - Neurological Institute
state: New York
city: Charlotte
country: United States
facility: Carolina Neurosurgery & Spine Assoc.
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences - Department of Neurosurgery
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation Department of Neurological Surgery
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: The Hospital of the University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: Baptist Memorial Hospital
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: University of Texas M.D. Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Insitute
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health Systems - Department of Neurological Surgery
state: Virginia
city: Seattle
country: United States
facility: Benaroya Research Institute at Virginia Mason Medical Center
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Department of Neurosurgery
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinic
state: Wisconsin
city: Calgary
country: Canada
facility: Calgary Health Region
state: Alberta
city: Edmonton
country: Canada
facility: Walter MacKenzie Health Sciences Center
state: Alberta
city: Winnepeg
country: Canada
facility: Cancer Care Manitoba
state: Manitoba
city: London
country: Canada
facility: London Regional Cancer Center
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook and Women's College Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Toronto
country: Canada
facility: Toronto Western Hospital Division of Neurosurgery
city: Dresden
country: Germany
facility: Techniche Universität Dresden Klinik und Poliklinik für Neurochirurgie
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf - Klinik für Neurochirurgie
city: Heidelberg
country: Germany
facility: Klinikum der Universität Heidelberg
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein - Klinik für Neurochirurgie
city: München
country: Germany
facility: Ludwig-Maximilians-Universität München - Klinikum Großhadern - Neurochirurgische Klinik und Poliklinik
city: Petach Tikva
country: Israel
facility: Rabin Medical Center - Department of Neurosurgery
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center (TASMC)
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center - Department of Neurosurgery
city: Groningen
country: Netherlands
facility: Academisch Ziekenhuis Groningen Afd. Neurochirurgie
city: Rotterdam
country: Netherlands
facility: Erasmus University MC, Rotterdam
city: Glasgow
country: United Kingdom
facility: Institute of Neurological Sciences
city: Liverpool
country: United Kingdom
facility: The Walton Centre for Neurology & Neurosurgery
Study officials:
References: