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

Sponsor

Abramson Cancer Center of the University of Pennsylvania (Other)

Overall Status

Completed

CT.gov ID

NCT00128635

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Duration (Months)

5.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Radiation: iodine I 131 monoclonal antibody TNT-1/B	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

22 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2005

Actual Study Completion Date :

Oct 1, 2007

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose based on CTCAE v3.0 weekly for 8 weeks then every 8 weeks []

Secondary Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham	Birmingham	Alabama	United States	35294
2	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
3	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096
4	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104-4283

Sponsors and Collaborators

Abramson Cancer Center of the University of Pennsylvania
National Cancer Institute (NCI)

Investigators

Study Chair: Robert A. Lustig, MD, Abramson Cancer Center of the University of Pennsylvania
: Kevin Judy, MD, Abramson Cancer Center of the University of Pennsylvania