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

Sponsor

INSYS Therapeutics Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT00076986

Collaborator

(none)

300

Enrollment

Locations

36.9

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma Multiforme	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)	Phase 3

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 Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Feb 1, 2004

Actual Primary Completion Date :

Mar 1, 2007

Actual Study Completion Date :

Mar 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Karnofsky Performance Score ≥ 70,
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:

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.

Contacts and Locations

Locations

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