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

Brain and Central Nervous System Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00128635
• Other study ID #: CDR0000438768
• Secondary ID: NABTT-0404
• Status: Completed
• Phase: Phase 1
• First received: August 8, 2005
• Last updated: February 17, 2016
• Start date: October 2005
• Est. completion date: October 2007

Study information

• Verified date: May 2007
• Source: Abramson Cancer Center of the University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Glioblastoma
• Nervous System Neoplasms

Intervention

Radiation:
• iodine I 131 monoclonal antibody TNT-1/B

Locations

Country	Name	City	State
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham	Birmingham	Alabama
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (2)

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

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose based on CTCAE v3.0 weekly for 8 weeks then every 8 weeks			Yes
Secondary	Biodistribution and radiation dosimetry by blood, urine, and whole body scans daily for 10 days			No
Secondary	Toxicity by CTCAE v3.0 weekly for 12 weeks then every 8 weeks			Yes
Secondary	Overall survival, median time of survival, and percent alive at 6 months			No