Iodine I 131 Monoclonal Antibody TNT-1/B in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme

Study Overview
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Brief Summary
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RATIONALE: Radiolabeled monoclonal antibodies, such as iodine I 131 monoclonal antibody TNT-1/B (^131I MOAB TNT-1/B), can find tumor cells and carry tumor-killing substances to them without harming normal cells. This may be an effective treatment for glioblastoma multiforme. PURPOSE: This phase I trial is studying the side effects and best dose of ^131I MOAB TNT-1/B in treating patients with progressive or recurrent glioblastoma multiforme.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose of iodine I 131 monoclonal antibody TNT-1/B in patients with progressive or recurrent glioblastoma multiforme. Secondary Determine the biodistribution and radiation dosimetry of this drug in these patients. Determine the toxicity and tolerability of this drug in these patients. Determine the overall survival, median time of survival, and 6-month survival of patients treated with this drug. OUTLINE: This is an open-label, multicenter, dose-escalation study of therapeutic doses of iodine I 131 monoclonal antibody TNT-1/B (^131I MOAB TNT-1/B). The first 12 patients accrued to the study undergo stereotactic placement of 2 catheters within the contrast-enhancing tumor on day 0. These patients then receive an imaging dose of ^131I MOAB TNT-1/B interstitially over approximately 25 hours on day 1 followed by dosimetry, biodistribution evaluations, and whole body imaging over an 8-10 day period. Beginning at least 2 weeks, but no more than 4 weeks later, all patients undergo catheter placement as above. One day later, patients receive a therapeutic dose of ^131I MOAB TNT-1/B interstitially over approximately 25 hours. Cohorts of 3-6 patients receive escalating therapeutic doses of ^131I MOAB TNT-1/B until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 10 patients are treated at the MTD. After completion of study treatment, patients are followed weekly for 3 weeks, at 6 weeks, at 4, 8, and 12 weeks (for the first 12 patients accrued to the study), every 4 weeks until disease progression, and then every 8 weeks thereafter. PROJECTED ACCRUAL: Approximately 22 patients will be accrued for this study.

Official Title
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An Open-Label, Dose Confirmation and Dosimetry Study of Interstitial 131 I-chTNT-1/B MAb (COTARA(TM)) For the Treatment of Glioblastoma Multiforme (GBM) at 1st or 2nd Relapse

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Radiation: iodine I 131 monoclonal antibody TNT-1/B


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed glioblastoma multiforme Focal disease Progressive or recurrent disease after prior treatment with radiotherapy and/or chemotherapy Low-grade astrocytoma that progressed to glioblastoma multiforme after prior radiotherapy and/or chemotherapy allowed Gross tumor volume 5-60 mL No intraventricular tumor, infratentorial tumor, or tumor that communicates with the ventricles No bilateral non-contiguous gadolinium-enhancing tumor No diffuse disease, defined as any satellite lesion > 1.5 cm from the anticipated location of a catheter tip OR > 2 satellite lesions No ventricular invasion outside the anticipated radiotherapy volume PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 60-100% Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9.0 g/dL Hepatic Bilirubin ≤ 1.5 mg/dL AST and ALT ≤ 2.5 times upper limit of normal (ULN) Hepatitis B negative No evidence of active hepatitis Renal Creatinine ≤ 1.7 mg/dL BUN ≤ 2 times ULN Cardiovascular No uncontrolled hypertension No unstable angina pectoris No uncontrolled cardiac dysrhythmia Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Able to undergo MRI Mini Mental State Exam score ≥ 15 No serious infection No other medical illness that would preclude study participation No other malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer No psychological or sociological condition, addictive disorder, or other condition that would preclude study compliance No known or suspected allergy to study drug or iodine No known HIV positivity PRIOR CONCURRENT THERAPY: Biologic therapy No prior monoclonal antibodies No prior local immunotherapy or treatment with the following biologic agents: Immunotoxins Immunoconjugates Antiangiogenesis compounds Antisense agents Peptide receptor antagonist Interferons Interleukins Tumor infiltrating lymphocytes Lymphokine-activated killer cells Gene therapy Chemotherapy See Disease Characteristics At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) At least 3 months since prior polifeprosan 20 with carmustine implant (Gliadel wafer^® ) Endocrine therapy Must be maintained on a stable corticosteroid dose (approximately 4 mg) for ≥ 2 weeks before study entry Radiotherapy See Disease Characteristics At least 3 months since prior radiotherapy No prior brachytherapy or radiosurgery Surgery At least 4 weeks since prior surgery Other Recovered from all prior therapy At least 1 month since prior investigational agents No more than 2 prior treatment regimens No other prior local therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Radiation: iodine I 131 monoclonal antibody TNT-1/B|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose based on CTCAE v3.0 weekly for 8 weeks then every 8 weeks |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biodistribution and radiation dosimetry by blood, urine, and whole body scans daily for 10 days |  |  | 
| Toxicity by CTCAE v3.0 weekly for 12 weeks then every 8 weeks |  |  | 
| Overall survival, median time of survival, and percent alive at 6 months |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult glioblastoma, adult gliosarcoma, adult giant cell glioblastoma, recurrent adult brain tumor