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

NCT ID: NCT00128635

Last Updated: 2016-02-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-10-31
• Study Completion Date: 2007-10-31

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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

iodine I 131 monoclonal antibody TNT-1/B

Intervention Type: RADIATION

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Abramson Cancer Center at Penn Medicine

OTHER

Sponsor Role: lead

Principal Investigators

Robert A. Lustig, MD

Role: STUDY_CHAIR

Abramson Cancer Center at Penn Medicine

Kevin Judy, MD

Role:

Abramson Cancer Center at Penn Medicine

Locations

Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham

Birmingham, Alabama, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

NABTT-0404

Identifier Type: -

Identifier Source: secondary_id

CDR0000438768

Identifier Type: -

Identifier Source: org_study_id