A Phase I/II Trial of Arsenic Trioxide and Temozolomide in Combination With Radiation Therapy for Patients With Malignant Gliomas
- Determine the maximum tolerated dose (MTD) of arsenic trioxide and temozolomide when
combined with radiotherapy in patients with resected supratentorial malignant glioma.
- Determine the toxicity of this regimen in these patients. (Phase I)
- Determine the 6- and 12-month progression-free survival of patients treated with this
regimen once an MTD is reached. (Phase II)
- Determine the radiographic response for patients treated with the above regimen. (Phase
- Determine the safety of this regimen in these patients. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of arsenic trioxide and temozolomide
followed by a phase II study.
- Phase I: Patients undergo radiotherapy once daily 5 days a week and receive oral
temozolomide once daily for approximately 6½ weeks. Patients also receive arsenic
trioxide IV over 1-4 hours once daily, 5 days a week in week 1 and then twice a week in
weeks 2-7. Beginning within 3-5 weeks after completion of radiotherapy, patients
receive oral temozolomide once daily on days 1-5. Treatment with temozolomide repeats
every 28 days for up to 1 year in the absence of disease progression and unacceptable
Cohorts of 3-6 patients receive escalating doses of arsenic trioxide and temozolomide until
the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding
that at which 1 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients undergo radiotherapy and receive arsenic trioxide and temozolomide
as in phase I at the MTD. Patients then receive temozolomide as in phase I for up to 1
year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for 1 year.
PROJECTED ACCRUAL: A total of 12-18 patients will be accrued for the phase I portion of this
study. A total of 25 patients will be accrued for the phase II portion of this study.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of arsenic trioxide and temozolomide in combination with radiotherapy
Escalating doses of study drug until dose limiting toxicities are observed.
Toxicity evaluated prior to each treatment cycle
Jeffrey Raizer, MD
United States: Federal Government
|Robert H. Lurie Comprehensive Cancer Center at Northwestern University||Chicago, Illinois 60611|
|Hematology-Oncology Associates of Illinois||Chicago, Illinois 60611-2998|
|Edward Cancer Center||Naperville, Illinois 60540|