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

Sponsor

TransMolecular (Industry)

Overall Status

Unknown status

CT.gov ID

NCT00114309

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

3.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Malignant Glioma Glioblastoma Multiforme GBM Anaplastic Astrocytoma Oligo-Astrocytoma Gliosarcoma	Drug: 131-I-TM-601 Drug: 131I-TM601	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

66 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Nov 1, 2004

Actual Primary Completion Date :

Mar 1, 2009

Anticipated Study Completion Date :

Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 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. Other Names: chlorotoxin
Experimental: 2 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. Other Names: chlorotoxin

Arm

Intervention/Treatment

Experimental: 1

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.

Other Names:

chlorotoxin

Experimental: 2

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.

Other Names:

chlorotoxin

Outcome Measures

Primary Outcome Measures

Determine Maximum Tolerated Dose (MTD) of 131-I-TM-601 administered intracavitary to patients with recurrent high-grade glioma [28 days post last dose]
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]
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]
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]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294-3410
2	City of Hope	Duarte	California	United States	91010
3	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
4	Florida Hospital Cancer Institute	Orlando	Florida	United States	32804
5	Moffitt Cancer Center	Tampa	Florida	United States	33612
6	Emory University	Atlanta	Georgia	United States	30322
7	Northwestern University	Chicago	Illinois	United States	60611
8	University of Chicago	Chicago	Illinois	United States	60637
9	Johns Hopkins Medical Center	Baltimore	Maryland	United States	21287
10	Tufts-New England Medical Center	Boston	Massachusetts	United States	02111
11	Henry Ford Hospital	Detroit	Michigan	United States	48202
12	Lacks Cancer Center at St. Mary's Health Care	Grand Rapids	Michigan	United States	49503
13	St. Louis Hospital	St. Louis	Missouri	United States	63110
14	Washington University Medical Center	St. Louis	Missouri	United States	63110
15	Columbia University Medical Center	New York	New York	United States	10032
16	Carolina Neurosurgery and Spine	Charlotte	North Carolina	United States	28204
17	Mary Crowley Medical Research Center	Dallas	Texas	United States	75246
18	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
19	University of Washington	Seattle	Washington	United States	98195-6470