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
18 Years
N/A
Both
Brain and Central Nervous System Tumors
Trial Information
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
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.
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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose based on CTCAE v3.0 weekly for 8 weeks then every 8 weeks
Safety Issue:
Yes
Principal Investigator
Robert A. Lustig, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Abramson Cancer Center of the University of Pennsylvania
Authority:
United States: Federal Government
Study ID:
CDR0000438768
NCT ID:
NCT00128635
Start Date:
October 2005
Completion Date:
October 2007
Related Keywords:
- Brain and Central Nervous System Tumors
- adult glioblastoma
- adult gliosarcoma
- adult giant cell glioblastoma
- recurrent adult brain tumor
- Glioblastoma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
Name | Location |
|---|---|
| Abramson Cancer Center of the University of Pennsylvania | Philadelphia, Pennsylvania 19104-4283 |
| Winship Cancer Institute of Emory University | Atlanta, Georgia 30322 |
| Wake Forest University Comprehensive Cancer Center | Winston-Salem, North Carolina 27157-1096 |
| Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham | Birmingham, Alabama 35294 |
