iodine i 131 monoclonal antibody tnt-1/b in treating patients with progressive or recurrent glioblastoma multiforme

Conditions: Brain and Central Nervous System Tumors

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.

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.

Eligibility 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

Keywords: adult glioblastoma adult gliosarcoma adult giant cell glioblastoma recurrent adult brain tumor