Surgery Followed by Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

Phase I Brachytherapy Dose Escalation Using The GliaSite RTS In Newly Diagnosed Glioblastoma Multiforme In Conjunction With External Beam Radiation Therapy

RATIONALE: Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. External-beam radiation therapy uses high-energy x-rays to kill tumor cells. Combining internal radiation with external-beam radiation therapy may kill any remaining tumor cells following surgery.

PURPOSE: Phase I trial to study the effectiveness of combining internal radiation therapy with external-beam radiation therapy in treating patients who have undergone surgery for glioblastoma multiforme.

Study Overview

• Status: Completed
• Conditions: Brain and Central Nervous System Tumors
• Intervention / Treatment: Radiation: radiation therapy; Procedure: conventional surgery; Radiation: brachytherapy

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose of brachytherapy administered via GliaSite RTS™ applicator followed by external beam radiotherapy in patients with newly diagnosed glioblastoma multiforme.
• Determine the acute and chronic toxicity of brachytherapy administered via GliaSite RTS™ in these patients.
• Determine the survival rate of patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of brachytherapy.

Patients undergo craniotomy for histologic confirmation of glioblastoma multiforme, surgical resection, and placement of a GliaSite RTS™ applicator that includes Iotrex™.

Beginning 3-21 days after surgery, patients undergo brachytherapy via the GliaSite RTS™ applicator. Within 30 days of brachytherapy (no more than 60 days after resection) patients undergo external beam radiotherapy 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 5-10 patients receive escalating doses of brachytherapy until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 5 or 3 of 10 patients experience dose-limiting toxicity.

Patients are followed at 21-35 days, every 2 months for 1 year, and then for survival.

PROJECTED ACCRUAL: A total of 15-100 patients will be accrued for this study.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3295
      • University of Alabama at Birmingham Comprehensive Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center and Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Hospital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157-1082
      • Comprehensive Cancer Center at Wake Forest University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center at University of Pennsylvania Medical Center
  • Texas
    • San Antonio, Texas, United States, 78284-7811
      • University of Texas Health Science Center at San Antonio

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:

• Clinically suspected supratentorial grade IV glioblastoma multiforme

• Candidate for maximal surgical resection of tumor mass

  • Expected residual enhancing tumor must be within the expected brachytherapy treatment volume
  • Resection must not be expected to result in a new permanent neurologic deficit
• No clearly multi-focal disease (2 or more separate foci of contrast-enhancing tumor not all within the expected brachytherapy prescription volume by MRI)
• No enhancing tumor greater than 1 cm beyond the midline by MRI
• No grossly or radiographically apparent leptomeningeal spread and/or ventricular invasion outside the anticipated radiation treatment volume
• No marked edema by MRI with significant shift that is not anticipated to be corrected by resection

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Not specified

Renal

• Creatinine no greater than 1.7 mg/dL
• BUN no greater than 2 times upper limit of normal

Cardiovascular

• No uncontrolled hypertension
• No unstable angina pectoris
• No uncontrolled cardiac dysrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Mini mental state exam score at least 15
• No other concurrent medical illness that would preclude study participation
• No concurrent serious infection
• No other malignancy within the past 5 years except curatively treated carcinoma in situ of the cervix or nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No immunotherapy prior to, during, or within 90 days after brachytherapy

• No biologic therapy with any of the following prior to, during, or within 90 days after brachytherapy :

  • Immunotoxins
  • Immunoconjugates
  • Antiangiogenesis compounds
  • Peptide receptor antagonists
  • Interferons
  • Interleukins
  • Tumor-infiltrating lymphocytes
  • Lymphokine-activated killer cells
  • Gene therapy
  • Antisense agents

Chemotherapy

• No chemotherapy or polifeprosan 20 with carmustine implant (Gliadel wafers) prior to, during, or within 90 days after brachytherapy

Endocrine therapy

• No hormonal therapy prior to, during, or within 90 days after brachytherapy
• Concurrent corticosteroids to improve quality of life allowed

Radiotherapy

• No other radiotherapy prior to, during, or within 90 days after brachytherapy

Surgery

• See Disease Characteristics
• No radiosurgery prior to, during, or within 90 days after brachytherapy

Other

• No other investigational agents directed at the brain tumor prior to, during, or within 90 days after brachytherapy
• Concurrent noncytotoxic therapy to improve quality of life allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: October 1, 2003

Study Registration Dates

• First Submitted: January 27, 2003
• First Submitted That Met QC Criteria: January 27, 2003
• First Posted (Estimate): January 28, 2003

Study Record Updates

• Last Update Posted (Estimate): February 9, 2009
• Last Update Submitted That Met QC Criteria: February 6, 2009
• Last Verified: July 1, 2004

More Information

Terms related to this study

• Keywords: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Nervous System Neoplasms; Central Nervous System Neoplasms
• Other Study ID Numbers: CDR0000269300; NABTT-2105; JHOC-NABTT-2105