Radiolabeled Monoclonal Antibody Therapy After Radiation Therapy in Treating Patients With Primary Brain Tumors

Darell D. Bigner, MD, PhD

Status and phase: Completed; Phase 1

Conditions: Neuroblastoma; Brain and Central Nervous System Tumors

Treatments: Drug: carmustine; Procedure: surgical procedure; Radiation: iodine I 131 monoclonal antibody 81C6; Drug: irinotecan hydrochloride

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00003484

DUMC-1373-97-9 (Other Identifier)

DUMC-1533-02-8R5ER (Other Identifier)

DUMC-1533-01-8R4 (Other Identifier)

Pro00008915

CDR0000066522 (Other Identifier)

NCI-G98-1472 (Other Grant/Funding Number)

5P0NS20023 (Other Grant/Funding Number)

DUMC-97107 (Other Identifier)

DUMC-1533-00-8R3 (Other Identifier)

DUMC-1570-99-9R2 (Other Identifier)

DUMC-1408-98-9R1 (Other Identifier)

Details and patient eligibility

About

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

PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody after radiation therapy in treating patients with newly diagnosed primary brain tumors that can be surgically resected.

Full description

OBJECTIVES:

• Determine the toxicity of iodine I 131 monoclonal antibody 81C6 delivered via the intracranial resection cavity in patients with newly diagnosed primary malignant brain tumors after surgery and radiotherapy.
• Determine objective therapeutic responses of these patients to this treatment.

OUTLINE: This is a dose escalation study of iodine I 131 antitenascin monoclonal antibody 81C6 (I 131 MAb 81C6).

Within 2-4 weeks after completion of external beam radiotherapy, patients undergo surgical resection of the tumor or brain metastasis, at which time an indwelling intracranial resection cavity catheter is placed. A single dose of I 131 MAb 81C6 is delivered via the intralesional catheter.

Cohorts of 3-6 patients receive escalating doses of I 131 MAb 81C6 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities.

After the MTD has been established, patients in the phase II portion of the study receive therapy as in phase I.

Beginning 4 weeks after the monoclonal antibody treatment, patients begin chemotherapy. Patients receive carmustine IV over 1 hour on day 1 and irinotecan IV over 90 minutes once weekly for 4 weeks. Treatment is repeated every 6 weeks for at least 4 courses in the absence of disease progression.

Patients are followed initially at 4 weeks, then every 6 weeks for 1 year.

PROJECTED ACCRUAL: A total of 41 patients will be accrued for this study.

Enrollment: 21 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed newly diagnosed supratentorial primary malignant brain tumor
• No infratentorial tumors, infiltrating tumors, tumors with subependymal spread, or multifocal tumors
• Candidate for surgical resection
• Prior external beam radiotherapy to site of measurable disease or resection site in the nervous system required
• Presence of tenascin in the tumor demonstrated by immunohistology with either a polyclonal rabbit antitenascin antibody or monoclonal antibody 81C6

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 50-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1000/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin less than 1.5 mg/dL
• Alkaline phosphatase less than 1.5 times normal
• Lactic dehydrogenase less than 1.5 times normal
• SGOT less than 1.5 times normal

Renal:

• Creatinine less than 1.2 mg/dL

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No iodine allergies

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Concurrent corticosteroids allowed, but must be on stable dose for at least 10 days

Radiotherapy:

• See Disease Characteristics

Surgery:

• See Disease Characteristics

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)