Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Primary Brain Tumors

NCT ID: NCT00003478

Last Updated: 2013-02-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1997-10-31
• Study Completion Date: 2007-07-31

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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

conventional surgery

Intervention Type: PROCEDURE

iodine I 131 monoclonal antibody 81C6

Intervention Type: RADIATION

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Darell D. Bigner, MD, PhD

Role: STUDY_CHAIR

Duke Cancer Institute

Locations

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Countries

United States

Other Identifiers

DUMC-1529-01-8R4

Identifier Type: -

Identifier Source: secondary_id

DUMC-1363-97-9

Identifier Type: -

Identifier Source: secondary_id

DUMC-1409-98-9R1

Identifier Type: -

Identifier Source: secondary_id

DUMC-1529-00-8R3

Identifier Type: -

Identifier Source: secondary_id

DUMC-1630-99-9R2

Identifier Type: -

Identifier Source: secondary_id

DUMC-97112

Identifier Type: -

Identifier Source: secondary_id

NCI-5950NS20023

Identifier Type: -

Identifier Source: secondary_id

NCI-G98-1471

Identifier Type: -

Identifier Source: secondary_id

CDR0000066515

Identifier Type: OTHER

Identifier Source: secondary_id

1529

Identifier Type: -

Identifier Source: org_study_id