Arsenic Trioxide, Temozolomide, and Radiation Therapy in Treating Patients With Malignant Glioma That Has Been Removed By Surgery
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.
Brain and Central Nervous System Tumors
Drug: arsenic trioxide
Radiation: radiation therapy
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Trial of Arsenic Trioxide and Temozolomide in Combination With Radiation Therapy for Patients With Malignant Gliomas|
- Maximum tolerated dose of arsenic trioxide and temozolomide in combination with radiotherapy [ Time Frame: Toxicity evaluated prior to each treatment cycle ] [ Designated as safety issue: Yes ]Escalating doses of study drug until dose limiting toxicities are observed.
- Collect data on the toxicity of arsenic and temozolomide during radiation therapy [ Time Frame: Toxicity evaluated prior to each treatment cycle ] [ Designated as safety issue: Yes ]Toxicity of this drug combination during radiation therapy will be assessed.
- Assess serum biomarkers and correlate with tumor tissue [ Time Frame: At baseline, during radiation therapy, and prior to each cycle of chemotherapy ] [ Designated as safety issue: No ]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.
- Determine progression free survival at 6 and 12 months [ Time Frame: At 6 and 12 months after beginning chemotherapy ] [ Designated as safety issue: No ]Patients will undergo an MRI and neurological evaluation every 6 months while on chemotherapy.
- Determine time to disease progression [ Time Frame: At 6 and 12 months after beginning chemotherapy ] [ Designated as safety issue: No ]Disease status will be assessed by MRI and neurological examination every 6 months until disease progression.
- To determine overall survival [ Time Frame: Every 6 months while on treatment ] [ Designated as safety issue: No ]Survival status will be evaluated every 6 months while on treatment.
- To determine radiographic response to study regimen [ Time Frame: Every 6 months while on treatment ] [ Designated as safety issue: No ]Radiographic response will be assessed by MRI every 6 months while on treatment
- To collect safety data during the radiation therapy phase [ Time Frame: Weekly during radiation therapy ] [ Designated as safety issue: Yes ]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 [ Time Frame: At baseline, before and after radiation therapy, and every 2 cycles during chemotherapy ] [ Designated as safety issue: No ]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.
|Study Start Date:||May 2005|
|Estimated Study Completion Date:||May 2017|
|Estimated Primary Completion Date:||May 2016 (Final data collection date for primary outcome measure)|
Experimental: Radiation + temozolomide and arsenic trioxide
Radiation therapy followed by the combination of temozolomide and arsenic trioxide at the maximum tolerated dose determined in phase 1
Drug: arsenic trioxide
Arsenic trioxide administered intravenously at a dose of 0.20mg/kg Daily x 5 week then twice per week
Other Names:Drug: temozolomide
Temozolomide administered orally once per day 1 hour prior to radiation therapy at a dose of 75 mg/m2 x 42 days; at a dose of 200mg/m2 for 5 days every cycle (1 cycle = 28 days) after radiation therapy
Other Names:Radiation: radiation therapy
All patients will receive 5940-6120 cGy of radiation therapy as 28-33 treatments/fractions (180-200 cGy/treatment) depending on whether they receive standard 3-D conformal radiation therapy or intensity modulated radiation therapy.
- 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)
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00275067
|United States, Illinois|
|Hematology-Oncology Associates of Illinois|
|Chicago, Illinois, United States, 60611-2998|
|Robert H. Lurie Comprehensive Cancer Center at Northwestern University|
|Chicago, Illinois, United States, 60611-3013|
|Edward Cancer Center|
|Naperville, Illinois, United States, 60540|
|Principal Investigator:||Jeffrey Raizer, MD||Northwestern University|