131-I-TM-601 Study in Adults With Recurrent High-Grade Glioma - Full Text View

Sponsored by:	TransMolecular
Information provided by:	TransMolecular
ClinicalTrials.gov Identifier:	NCT00114309

Purpose

This drug is being developed to treat a type of brain cancer, glioma. This study was developed to evaluate the safety, time to disease progression and survival rates after treatment.

Condition	Intervention	Phase
Malignant Glioma Glioblastoma Multiforme GBM Anaplastic Astrocytoma Oligo-Astrocytoma Gliosarcoma	Drug: 131-I-TM-601 Drug: 131I-TM601	Phase II

MedlinePlus related topics: Brain Cancer Cancer

Drug Information available for: Iodine Cadexomer iodine Sodium iodide I 131

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Phase II Open-Label, Multiple-Dose Study of Intracavitary Administered 131-I-TM-601 in Adult Patients With Recurrent High-Grade Glioma

Further study details as provided by TransMolecular:

Primary Outcome Measures:

Determine Maximum Tolerated Dose (MTD) of 131-I-TM-601 administered intracavitary to patients with recurrent high-grade glioma [ Time Frame: 28 days post last dose ] [ Designated as safety issue: Yes ]
Determine the toxicity of a three (3) and six (6) dose cycle of 131-I-TM-601 administrations into the tumor resection site of patients with recurrent high-grade glioma [ Time Frame: 28 days post last dose and then at 3 month intervals from first dose, until disease progression ] [ Designated as safety issue: Yes ]
Evaluate the 6 and 12-month rate of progression and survival of patients with recurrent high-grade glioma treated with a three (3) or six (6) dose cycle of 131-I-TM-601 [ Time Frame: at 3 month intervals from first dose administration, until disease progression ] [ Designated as safety issue: No ]
Evaluate the overall time to progression and death of patients with recurrent high-grade glioma treated with either a three (3) or six (6) dose cycle of 131-I-TM-601 [ Time Frame: at 3 month intervals until disease progression ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Evaluate if either a three (3) or six (6) dose cycle of 131-I-TM-601 affects Quality of Life [ Time Frame: 3 month intervals until disease progression ] [ Designated as safety issue: No ]

Estimated Enrollment:	66
Study Start Date:	November 2004
Estimated Study Completion Date:	December 2008
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 3 Dose Regimen	Drug: 131-I-TM-601 131I-TM601, in solution, delivered intracavitarily following surgical resection 3 weekly administrations, 0.8 mg TM601 and 40mCi 131Iodine, per dose.
2: Experimental 6 Dose Regimen	Drug: 131I-TM601 131I-TM601, in solution, delivered intracavitarily following surgical resection 6 weekly administrations, 0.8 mg TM601 and 40mCi 131Iodine, per dose.

Detailed Description:

This phase II trial was designed in two sequences. The first sequence, which is now complete to accrual was an open-label, dose escalation, multi-dose study and treated 12 evaluable patients with high-grade glioma.

The second sequence is currently open and accruing eligible subjects with high-grade glioma. The trial is an open-label, randomized study and will accrue a total of 54 evaluable patients. Eligible subjects will be randomized to receive either 3 or 6 injections of 131-I labeled TM-601 (131-I-TM-601), in weekly intervals at the dose determined in the first sequence of the trial. Patients will undergo debulking surgery and placement of a ventricular access device into the tumor cavity for administration of 131I-TM-601. Patients who participated in the first sequence are not eligible to participate in the second sequence of the study.

High-grade gliomas include; glioblastoma multiforme, anaplastic astrocytoma, oligoastrocytoma or gliosarcoma.

Patients will undergo follow-up clinical examinations and magnetic resonance imaging (MRI) assessments, at defined intervals, until 12 months after the first study dose.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patient must have a histologically confirmed unilateral, supratentorial malignant glioma (grade 3 or 4, anaplastic astrocytoma, gliosarcoma, glioblastoma multiforme or malignant oligoastrocytoma)
Patient must have glioma progression or recurrence following radiotherapy that was no less than 50 Gy (+/- chemotherapy; +/- surgery)
Patient must be a candidate for resection of the recurrent tumor (surgical requirements are detailed in the study protocol)
Imaging must show recurrent, unilateral, supratentorial tumor(s)
There is no diffuse leptomeningeal disease
For patients with previous radiosurgery or enhanced radiotherapy, based on neurosurgeon's judgment, the area of enhancement can be removed during the surgery
Patient must have recovered from toxicity of prior therapy
Patient must be > 18 years of age.
Patient has a Karnofsky Performance Status greater than or equal to 60%
Patient must have a life expectancy of at least 3 months
Patient has no uncontrolled seizures or other neurological conditions which would interfere with evaluation
Patient is not currently receiving, or is not anticipated to receive, concomitant anticancer agent(s) during the course of this study
Patient must have given informed consent

Exclusion Criteria:

Patient with concurrent malignancy (except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of cervix and/or breast) or patients with prior malignancies that have not been disease-free for five years
Patient has presence of non-contiguous satellite lesions
Patient with known allergy to iodine, iodine containing drugs or contrast agent
Patient with the potential for pregnancy or impregnating their partner and who do not agree to follow an acceptable birth control method to avoid conception
Pregnant or breast feeding females
Patient is not maintained on a stable corticosteroid regimen
New onset of conditions not present prior to surgery (as detailed in Study Protocol) which would make patient an inappropriate study candidate, or as determined by Investigator

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00114309

Locations

United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294-3410
United States, California
City of Hope
Duarte, California, United States, 91010
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
United States, Florida
Florida Hospital Cancer Institute
Orlando, Florida, United States, 32804
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
University of Chicago
Chicago, Illinois, United States, 60637
United States, Maryland
Johns Hopkins Medical Center
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Tufts-New England Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
Lacks Cancer Center at St. Mary's Health Care
Grand Rapids, Michigan, United States, 49503
United States, Missouri
St. Louis Hospital
St. Louis, Missouri, United States, 63110
Washington University Medical Center
St. Louis, Missouri, United States, 63110
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, North Carolina
Carolina Neurosurgery and Spine
Charlotte, North Carolina, United States, 28204
United States, Texas
Mary Crowley Medical Research Center
Dallas, Texas, United States, 75246
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
United States, Washington
University of Washington
Seattle, Washington, United States, 98195-6470

Sponsors and Collaborators

TransMolecular

Investigators

Principal Investigator:

John Fiveash, MD

University of Alabama at Birmingham

More Information

Publications of Results:

Mamelak AN, Rosenfeld S, Bucholz R, Raubitschek A, Nabors LB, Fiveash JB, Shen S, Khazaeli MB, Colcher D, Liu A, Osman M, Guthrie B, Schade-Bijur S, Hablitz DM, Alvarez VL, Gonda MA. Phase I single-dose study of intracavitary-administered iodine-131-TM-601 in adults with recurrent high-grade glioma. J Clin Oncol. 2006 Aug 1;24(22):3644-50.

Hockaday DC, Shen S, Fiveash J, Raubitschek A, Colcher D, Liu A, Alvarez V, Mamelak AN. Imaging glioma extent with 131I-TM-601. J Nucl Med. 2005 Apr;46(4):580-6.

Other Publications:

Mamelak AN, Jacoby DB. Targeted delivery of antitumoral therapy to glioma and other malignancies with synthetic chlorotoxin (TM-601). Expert Opin Drug Deliv. 2007 Mar;4(2):175-86. Review.

Lyons SA, O'Neal J, Sontheimer H. Chlorotoxin, a scorpion-derived peptide, specifically binds to gliomas and tumors of neuroectodermal origin. Glia. 2002 Aug;39(2):162-73.

Responsible Party:	TransMolecular, Inc. ( Susan Stewart, Vice President, Regulatory Affairs )
Study ID Numbers:	TM-601-002
Study First Received:	June 13, 2005
Last Updated:	July 1, 2008
ClinicalTrials.gov Identifier:	NCT00114309
Health Authority:	United States: Food and Drug Administration

Keywords provided by TransMolecular:

High grade recurrent glioma
Phase II
Multi-Center
Open label
Multiple dose

Brain Cancer
Brain Tumor
GBM
glioma

Study placed in the following topic categories:

Neuroectodermal Tumors
Brain Neoplasms
Glioblastoma
Glioblastoma multiforme
Astrocytoma
Neoplasms, Germ Cell and Embryonal

Iodine
Neuroepithelioma
Glioma
Gliosarcoma
Recurrence
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial

ClinicalTrials.gov processed this record on January 16, 2009