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.

Condition	Treatment or Intervention	Phase
Central Nervous System Tumor Brain Tumor	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: surgery  Procedure: radiation therapy  Procedure: isotope therapy  Procedure: monoclonal antibody therapy  Procedure: antibody therapy  Procedure: radioimmunotherapy  Drug: carmustine  Drug: iodine I 131 monoclonal antibody 81C6  Drug: irinotecan	Phase I Phase II

Further Study Details: 

OBJECTIVES: I. 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. II. Determine objective therapeutic responses of these patients to this treatment.

PROTOCOL 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.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY 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

--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

--Patient Characteristics--

Age: 18 and over

Performance status: Karnofsky 50-100%

Life expectancy: Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1000/mm3
• Platelet count greater than 100,000/mm3

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

North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States

Study chairs or principal investigators

Darell D. Bigner,  Study Chair,  Duke Comprehensive Cancer Center   

Study ID Numbers:  CDR0000066522; DUMC-1533-01-8R4; NCI-5P0NS20023; NCI-G98-1472; DUMC-1373-97-9; DUMC-1408-98-9R1; DUMC-1533-00-8R3; DUMC-1570-99-9R2; DUMC-97107
Record last reviewed:  April 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003484
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08