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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase I Study of Anti-Tenascin Monoclonal Antibody I-Labeled 81C6 Via Surgically Created Cystic Resection Cavity in the Treatment of Patients With Primary Brain Tumors After External Beam Radiotherapy

Conditions
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Brain and Central Nervous System Tumors, Neuroblastoma

Intervention / Treatment
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* Drug: carmustine
* Drug: irinotecan hydrochloride
* Procedure: surgical procedure
* Radiation: iodine I 131 monoclonal antibody 81C6


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: carmustine|nan|
|Drug: irinotecan hydrochloride|nan|
|Procedure: surgical procedure|nan|
|Radiation: iodine I 131 monoclonal antibody 81C6|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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localized resectable neuroblastoma, recurrent adult brain tumor, adult craniopharyngioma, adult medulloblastoma, adult meningioma, adult glioblastoma, adult oligodendroglioma, adult anaplastic astrocytoma, adult mixed glioma, adult pineal parenchymal tumor, adult central nervous system germ cell tumor, adult grade III meningioma, adult pilocytic astrocytoma, adult giant cell glioblastoma, adult gliosarcoma