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

Glioblastoma Multiforme Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00114309
• Other study ID #: TM-601-002
• Status: Active, not recruiting
• Phase: Phase 2
• First received: June 13, 2005
• Last updated: April 1, 2009
• Start date: November 2004
• Est. completion date: August 2009

Study information

• Verified date: April 2009
• Source: TransMolecular
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 66
• Est. completion date: August 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anaplastic Astrocytoma
• Astrocytoma
• GBM
• Glioblastoma
• Glioblastoma Multiforme
• Glioma
• Gliosarcoma
• Malignant Glioma
• Oligo-Astrocytoma

Intervention

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.
• 131I-TM601
131I-TM601, in solution, delivered intracavitarily following surgical resection 6 weekly administrations, 0.8 mg TM601 and 40mCi 131Iodine, per dose.

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Johns Hopkins Medical Center	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Tufts-New England Medical Center	Boston	Massachusetts
United States	Carolina Neurosurgery and Spine	Charlotte	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Mary Crowley Medical Research Center	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Lacks Cancer Center at St. Mary's Health Care	Grand Rapids	Michigan
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Columbia University Medical Center	New York	New York
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	University of Washington	Seattle	Washington
United States	St. Louis Hospital	St. Louis	Missouri
United States	Washington University Medical Center	St. Louis	Missouri
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
TransMolecular

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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-60 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine Maximum Tolerated Dose (MTD) of 131-I-TM-601 administered intracavitary to patients with recurrent high-grade glioma		28 days post last dose	Yes
Primary	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		28 days post last dose and then at 3 month intervals from first dose, until disease progression	Yes
Primary	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		at 3 month intervals from first dose administration, until disease progression	No
Primary	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		at 3 month intervals until disease progression	No
Secondary	Evaluate if either a three (3) or six (6) dose cycle of 131-I-TM-601 affects Quality of Life		3 month intervals until disease progression	No