Clinical trial NCT00114309: 131-I-TM-601 Study in Adults With Recurrent High-Grade Glioma
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Malignant Glioma
Glioblastoma Multiforme
GBM
Anaplastic Astrocytoma
Oligo-Astrocytoma
Gliosarcoma
Keywords: High grade recurrent glioma
Phase II
Multi-Center
Open label
Multiple dose
Brain Cancer
Brain Tumor
GBM
glioma
Lead sponsor: TransMolecular
Sponsor class: INDUSTRY
First posted: 2005-06-14
Enrollment: 66
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: 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.

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 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

Primary outcomes:
measure: Determine Maximum Tolerated Dose (MTD) of 131-I-TM-601 administered intracavitary to patients with recurrent high-grade glioma
timeFrame: 28 days post last dose
measure: 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
timeFrame: 28 days post last dose and then at 3 month intervals from first dose, until disease progression
measure: 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
timeFrame: at 3 month intervals from first dose administration, until disease progression
measure: 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
timeFrame: at 3 month intervals until disease progression
Secondary outcomes:
measure: Evaluate if either a three (3) or six (6) dose cycle of 131-I-TM-601 affects Quality of Life
timeFrame: 3 month intervals until disease progression
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Medical Center
state: Maryland
city: Boston
country: United States
facility: Tufts-New England Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Lacks Cancer Center at St. Mary's Health Care
state: Michigan
city: St. Louis
country: United States
facility: St. Louis Hospital
state: Missouri
city: St. Louis
country: United States
facility: Washington University Medical Center
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Charlotte
country: United States
facility: Carolina Neurosurgery and Spine
state: North Carolina
city: Dallas
country: United States
facility: Mary Crowley Medical Research Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Alabama at Birmingham
name: John Fiveash, MD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1517/17425247.4.2.175.
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. doi: 10.1002/glia.10083.
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-601 in adults with recurrent high-grade glioma. J Clin Oncol. 2006 Aug 1;24(22):3644-50. doi: 10.1200/JCO.2005.05.4569.
citation: 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.