Arsenic Trioxide, Temozolomide, and Radiation Therapy in Treating Patients With Malignant Glioma That Has Been Removed By Surgery
- Conditions
- Brain and Central Nervous System Tumors
- Interventions
- Registration Number
- NCT00275067
- Lead Sponsor
- Northwestern University
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving arsenic trioxide and temozolomide together with radiation therapy after surgery may kill any remaining tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of arsenic trioxide and temozolomide when given together with radiation therapy and to see how well they work in treating patients with malignant glioma that has been removed by surgery.
- Detailed Description
OBJECTIVES:
Primary
* Determine the maximum tolerated dose (MTD) of arsenic trioxide and temozolomide when combined with radiotherapy in patients with resected supratentorial malignant glioma. (Phase I)
* Determine the toxicity of this regimen in these patients. (Phase I)
Secondary
* 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 II)
* 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 toxicity.
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 50
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Radiation + temozolomide and arsenic trioxide radiation therapy Radiation therapy followed by the combination of temozolomide and arsenic trioxide at the maximum tolerated dose determined in phase 1 Radiation + temozolomide and arsenic trioxide arsenic trioxide Radiation therapy followed by the combination of temozolomide and arsenic trioxide at the maximum tolerated dose determined in phase 1 Radiation + temozolomide and arsenic trioxide temozolomide Radiation therapy followed by the combination of temozolomide and arsenic trioxide at the maximum tolerated dose determined in phase 1
- Primary Outcome Measures
Name Time Method Maximum tolerated dose of arsenic trioxide and temozolomide in combination with radiotherapy Toxicity evaluated prior to each treatment cycle Escalating doses of study drug until dose limiting toxicities are observed.
Assess serum biomarkers and correlate with tumor tissue At baseline, during radiation therapy, and prior to each cycle of chemotherapy Blood will be drawn at baseline, during radiation therapy, and prior to each cycle of chemotherapy to assess serum biomarkers and correlate with tumor tissue.
Collect data on the toxicity of arsenic and temozolomide during radiation therapy Toxicity evaluated prior to each treatment cycle Toxicity of this drug combination during radiation therapy will be assessed.
- Secondary Outcome Measures
Name Time Method Determine progression free survival at 6 and 12 months At 6 and 12 months after beginning chemotherapy Patients will undergo an MRI and neurological evaluation every 6 months while on chemotherapy.
To determine radiographic response to study regimen Every 6 months while on treatment Radiographic response will be assessed by MRI every 6 months while on treatment
To collect safety data during the radiation therapy phase Weekly during radiation therapy EKG's will be done once per week and labs twice per week during radiation therapy phase to evaluate safety data.
To evaluate a potential surrogate marker for outcomes At baseline, before and after radiation therapy, and every 2 cycles during chemotherapy Blood will be drawn to analyze methylation patterns as a surrogate marker for outcomes at baseline, before and after radiation therapy, and every 2 cycles during chemotherapy.
Determine time to disease progression At 6 and 12 months after beginning chemotherapy Disease status will be assessed by MRI and neurological examination every 6 months until disease progression.
To determine overall survival Every 6 months while on treatment Survival status will be evaluated every 6 months while on treatment.
Trial Locations
- Locations (3)
Hematology-Oncology Associates of Illinois
🇺🇸Chicago, Illinois, United States
Edward Cancer Center
🇺🇸Naperville, Illinois, United States
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
🇺🇸Chicago, Illinois, United States