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

Sponsor:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00128635

Purpose

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

Study Type:	Interventional
Study Design:	Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Cadexomer iodine Immunoglobulins Iodine Sodium iodide I 131 Globulin, Immune

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose based on CTCAE v3.0 weekly for 8 weeks then every 8 weeks [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Biodistribution and radiation dosimetry by blood, urine, and whole body scans daily for 10 days [ Designated as safety issue: No ]
Toxicity by CTCAE v3.0 weekly for 12 weeks then every 8 weeks [ Designated as safety issue: Yes ]
Overall survival, median time of survival, and percent alive at 6 months [ Designated as safety issue: No ]

Estimated Enrollment:	22
Study Start Date:	October 2005

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00128635

Locations

United States, Alabama
Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham
Birmingham, Alabama, United States, 35294
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, North Carolina
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

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

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier:	NCT00128635 History of Changes
Other Study ID Numbers:	CDR0000438768, NABTT-0404
Study First Received:	August 8, 2005
Last Updated:	February 6, 2009
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Glioblastoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases

Antibodies
Immunoglobulins
Antibodies, Monoclonal
Iodine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Trace Elements
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on February 09, 2012