Patient case: 84-year-old male with glioblastoma; genetic feature: CDK6

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

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.

Eligibility: 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

Relevance to patient case: not relevant