Malignant Neoplasms of Eye, Brain and Other Parts of Central Nervous System Clinical Trial
Official title:
A Phase III Study of Radiation Therapy (RT) and O6-Benzylguanine (O6-BG) Plus BCNU Versus RT and BCNU Alone for Newly Diagnosed Glioblastoma Multiforme (GBM) and Gliosarcoma
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor
cells. O6-benzylguanine may help carmustine kill more tumor cells by making tumor cells more
sensitive to the drug. It is not yet known whether radiation therapy and carmustine are more
effective with or without O6-benzylguanine.
PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy plus
carmustine with or without O6-benzylguanine in treating patients who have newly diagnosed
glioblastoma multiforme or gliosarcoma.
OBJECTIVES:
- Compare the overall survival, failure-free survival, and progression-free survival of
patients with newly diagnosed glioblastoma multiforme or gliosarcoma treated with
radiotherapy and carmustine with or without O6-benzylguanine.
- Compare the frequency and severity of toxic effects of these regimens in these
patients.
- Correlate the survival of these patients with the expression of O6-alkylguanine-DNA
alkyltransferase.
OUTLINE: This is a randomized study. Patients are stratified according to age (under 50 vs
50 and over), prior surgery (biopsy only vs resection), and Zubrod performance status (0-1
vs 2). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo radiotherapy daily 5 days a week over 7 weeks for a total of 34
fractions. Patients also receive chemotherapy comprising O6-benzylguanine IV over 1
hour followed 6 hours later by carmustine IV over 1 hour on day 1 of radiotherapy.
Chemotherapy repeats every 6 weeks for a maximum of 7 courses in the absence of disease
progression or unacceptable toxicity.
- Arm II: Patients undergo radiotherapy as in arm I. Patients receive carmustine IV as in
arm I.
Patients are followed at week 48, every 4 months for 1 year, and then every 6 months for 4
years.
PROJECTED ACCRUAL: A total of 375 patients will be accrued for this study within 5 years.
;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment