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

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

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.

Study Overview

• Status: Completed
• Conditions: Brain and Central Nervous System Tumors; Neuroblastoma
• Intervention / Treatment: Drug: irinotecan hydrochloride; Drug: carmustine; Procedure: surgical procedure; Radiation: iodine I 131 monoclonal antibody 81C6

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Collaborators and Investigators

• Sponsor: Darell D. Bigner, MD, PhD
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: September 1, 1997
• Primary Completion (ACTUAL): November 1, 2003
• Study Completion (ACTUAL): March 1, 2010

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: April 29, 2003
• First Posted (ESTIMATE): April 30, 2003

Study Record Updates

• Last Update Posted (ESTIMATE): April 23, 2015
• Last Update Submitted That Met QC Criteria: April 22, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma; recurrent adult brain tumor; adult anaplastic astrocytoma; adult central nervous system germ cell tumor; adult craniopharyngioma; adult medulloblastoma; adult meningioma; adult oligodendroglioma; adult grade III meningioma; adult mixed glioma; adult pilocytic astrocytoma; adult pineal parenchymal tumor; localized resectable neuroblastoma
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Brain Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Neuroblastoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Antibodies; Irinotecan; Antibodies, Monoclonal; Carmustine
• Other Study ID Numbers: Pro00008915; DUMC-1533-02-8R5ER (OTHER: Duke University IRB); DUMC-1533-01-8R4 (OTHER: Duke University IRB); DUMC-1373-97-9 (OTHER: Duke University IRB); DUMC-1408-98-9R1 (OTHER: Duke University IRB); DUMC-1533-00-8R3 (OTHER: Duke University IRB); DUMC-1570-99-9R2 (OTHER: Duke University IRB); DUMC-97107 (OTHER: Duke University Cancer Protocol Committee); 5P0NS20023 (OTHER_GRANT: National Cancer Institute); NCI-G98-1472 (OTHER_GRANT: National Cancer Institute); CDR0000066522 (OTHER: National Cancer Institute Record Identifier)