Clinical trial NCT00003478: Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Primary Brain Tumors
Official title: Phase I Study of Intra-Tumoral, Radiolabeled, Anti-Tenascin Monoclonal Antibody 81C6 in the Treatment of Patients With Malignant Primary Brain Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: recurrent adult brain tumor
adult brain stem glioma
adult medulloblastoma
adult glioblastoma
adult anaplastic astrocytoma
adult anaplastic ependymoma
adult anaplastic oligodendroglioma
adult mixed glioma
adult ependymoblastoma
adult giant cell glioblastoma
adult gliosarcoma
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies can locate tumor cells and deliver radioactive tumor-killing substances such as radioactive iodine to them without harming normal cells.

PURPOSE: This randomized phase I/II trial is studying the side effects, best way to give, and best dose of radiolabeled monoclonal antibody and to see how well it works in treating patients with primary brain tumors.

Detailed description: OBJECTIVES:

* Determine which one of two delivery techniques (bolus injection versus microinfusion) provides the greater distribution volume of iodine I 131 antitenascin monoclonal antibody 81C6 (I 131 MAb 81C6) administered intratumorally in patients with newly diagnosed or recurrent malignant primary brain tumors.
* Determine the maximum tolerated dose of I 131 MAb 81C6 delivered intratumorally in these patients.
* Evaluate the efficacy of I 131 MAB 81C6 delivered intratumorally in these patients.

OUTLINE: This is a randomized, dose-escalation study.

Patients are randomized to receive iodine I 131 antitenascin monoclonal antibody 81C6 (I 131 MAb 81C6) by one of two delivery techniques first, then crossover to receive the antibody by the other technique 3 days later. Each patient then receives a therapeutic dose by the most efficient method. Both methods are delivered via a stereotactically-placed intralesional catheter.

* Arm I: Bolus injection method
* Arm II: Microinfusion delivery method Cohorts of 3-6 patients receive escalating doses of I 131 MAb 81C6, with dose escalation occurring separately for each arm. After 10 patients are enrolled and the best method of administration is determined, all subsequent patients receive I 131 MAb 81C6 by that method, and the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more the 2 of 6 patients experience dose-limiting toxicity.

Patients with newly diagnosed tumors for which no effective conventional therapy exists, such as malignant glial tumors, are treated with external beam radiotherapy within 4 months after I 131 MAb 81C6 infusion. Patients with recurrent tumors receive no other therapy unless tumor progresses.

Patients are followed at 4, 8, 16, and 24 weeks and then every 12 weeks for one year.

PROJECTED ACCRUAL: At least 10 patients will be accrued for this study within 1 year.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically proven newly diagnosed or recurrent primary intracranial WHO grade III or IV glioma
* Reactivity of tumor cells with 81C6 demonstrated by immunohistology with either a polyclonal rabbit antibody or the monoclonal mouse antibody
* Radiographic evidence of a single lesion by MRI or CT scan

  * No greater than 2 to 5 cm
* No cerebral herniation syndrome
* Midline brain shift less than 0.5 cm

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Karnofsky 60-100%

Life expectancy:

* Not specified

Hematopoietic:

* Absolute neutrophil count greater than 1000/mm\^3
* Platelet count greater than 100,000/mm\^3
* Hemoglobin greater than 10 g/dL

Hepatic:

* Bilirubin less than 1.5 mg/dL
* Alkaline phosphatase less than 1.5 times normal
* SGOT less than 1.5 times normal

Renal:

* Creatinine less than 2.0 mg/dL

Other:

* Not pregnant or nursing
* Fertile patients must use effective contraception
* No allergies to iodine or local anesthetics

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No concurrent autologous bone marrow transplant

Chemotherapy:

* No more than 1 prior conventional or phase II chemotherapy regimen
* No prior phase I chemotherapy regimens
* At least 4 weeks since prior chemotherapy
* No concurrent systemic chemotherapy

Endocrine therapy:

* Corticosteroids allowed but must be on stable dose for at least 1 week

Radiotherapy:

* At least 3 months since radiotherapy to site of measurable disease in the nervous system, unless evidence of progression

Surgery:

* Not specified

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: Duke Cancer Institute
name: Darell D. Bigner, MD, PhD
role: STUDY_CHAIR
References: