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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: Brain and Central Nervous System Tumors

Treatments: Radiation: brachytherapy; Radiation: radiation therapy; Procedure: conventional surgery

Study type: Interventional

Funder types: NIH

Identifiers

NCT00053183

CDR0000269300

JHOC-NABTT-2105

NABTT-2105

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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