This phase I trial is studying the side effects and best dose of arsenic trioxide and radiation therapy in treating patients with newly diagnosed malignant glioma. Drugs such as arsenic trioxide may stop the growth of malignant glioma by stopping blood flow to the tumor. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining arsenic trioxide with radiation therapy may kill more tumor cells.
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of Arsenic Trioxide (ATO) when administered on a once a week schedule and a twice a week schedule in conjunction with radiation therapy to patients with newly diagnosed glioblastoma multiforme. II. To determine the toxicity of ATO when it is administered on a once a week schedule and a twice a week schedule in conjunction with radiation therapy in patients with newly diagnosed glioblastoma multiforme. SECONDARY OBJECTIVES: I. To determine the survival of patients with newly diagnosed glioblastoma multiforme receiving ATO when it is administered on a once a week schedule and a twice a week schedule in conjunction with radiation therapy. II. To evaluate the effect of ATO on tumor vasculature by using perfusion MRI. III. To describe the pharmacokinetics of ATO following weekly and twice weekly injection. OUTLINE: This is a nonrandomized, open-label, multicenter, dose-escalation study of arsenic trioxide. Patients are assigned to 1 of 2 treatment groups. Group A: Patients receive arsenic trioxide IV over 2 hours once weekly for 6 weeks. Group B: Patients receive arsenic trioxide at a lower dose IV over 2 hours twice weekly for 6 weeks. Patients in both groups also undergo radiotherapy once daily 5 days a week for 6 weeks. In both groups, cohorts of 3-6 patients receive escalating doses of arsenic trioxide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 3 of 6 patients experience dose-limiting toxicity. Patients are followed weekly for 4 weeks and then every 2 months thereafter.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
Given IV
Undergo radiation therapy
New Approaches to Brain Tumor Therapy Consortium
Baltimore, Maryland, United States
Maximum tolerated dose of ATO in conjunction with radiotherapy and optimum ATO dose for radiosensitization determined by dose-limiting toxicities
Results of the safety evaluation will be tabulated and displayed by dose level.
Time frame: 6 weeks
Proportion of patients with serious or life-threatening toxicities using the grading scale of Adverse Events Criteria
Results of the safety evaluation will be tabulated and displayed by dose level. The will be estimated along with 95% confidence intervals.
Time frame: Up to 6 years
Duration of survival with this treatment regimen
Non-parametric estimates of survival will be calculated.
Time frame: Up to 6 years
Overall event rates (hazards rates)
Will be estimated with 95% confidence intervals.
Time frame: Up to 6 years
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NONE
Enrollment
30