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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


Phase 1
18 Years
N/A
Not Enrolling
Both
Brain and Central Nervous System Tumors

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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 PennsylvaniaPhiladelphia, Pennsylvania  19104-4283
Winship Cancer Institute of Emory UniversityAtlanta, Georgia  30322
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
Lurleen Wallace Comprehensive Cancer at University of Alabama-BirminghamBirmingham, Alabama  35294