Clinical trial NCT00128635: Iodine I 131 Monoclonal Antibody TNT-1/B in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain and Central Nervous System Tumors
Keywords: adult glioblastoma
adult gliosarcoma
adult giant cell glioblastoma
recurrent adult brain tumor
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-08-10
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Maximum tolerated dose based on CTCAE v3.0 weekly for 8 weeks then every 8 weeks
Secondary outcomes:
measure: Biodistribution and radiation dosimetry by blood, urine, and whole body scans daily for 10 days
measure: Toxicity by CTCAE v3.0 weekly for 12 weeks then every 8 weeks
measure: Overall survival, median time of survival, and percent alive at 6 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham
state: Alabama
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Abramson Cancer Center at Penn Medicine
name: Robert A. Lustig, MD
role: STUDY_CHAIR
affiliation: Abramson Cancer Center at Penn Medicine
name: Kevin Judy, MD
References: