Brain and Central Nervous System Tumors
Conditions
Keywords
adult glioblastoma, adult gliosarcoma, adult giant cell glioblastoma, recurrent adult brain tumor
Brief summary
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
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.
Interventions
Sponsors
National Cancer Institute (NCI)
Abramson Cancer Center at Penn Medicine
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose based on CTCAE v3.0 weekly for 8 weeks then every 8 weeks | — |
Secondary
| Measure | 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 | — |
Countries
United States
Outcome results
None listed