Radiation Therapy, Arsenic Trioxide, and Temozolomide in Treating Patients With Newly Diagnosed High-Grade Glioma

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. 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. Arsenic trioxide and temozolomide may also make tumor cells more sensitive to radiation therapy. Giving radiation therapy together with combination chemotherapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of arsenic trioxide when given together with temozolomide and radiation therapy in treating patients with newly diagnosed high-grade glioma.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of arsenic trioxide when administered sequentially with temozolomide during radiotherapy in patients with newly diagnosed glioblastoma multiforme. Determine the dose-limiting toxicities of this regimen in these patients. OUTLINE: This is a dose-escalation study of arsenic trioxide. Patients undergo radiotherapy (may be intensity-modulated) on days 1-5. Patients also receive arsenic trioxide IV over 1-2 hours on days 1-5, and oral temozolomide on days 1-7. Treatment with radiotherapy, arsenic trioxide, and temozolomide repeats every week for up to 6 weeks in the absence of disease progression or unacceptable toxicity. Patients may then receive oral temozolomide on days 1-5. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression. After completion of study therapy, patients are followed periodically.

Official Title
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A Phase I Study of the Combination of Radiation Therapy (RT), Arsenic Trioxide (ATO) and Temozolomide (TMZ) in Patients With Newly-Diagnosed Glioblastoma Multiforme (GBM)

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: arsenic trioxide
* Drug: temozolomide
* Procedure: adjuvant therapy
* Radiation: intensity-modulated radiation therapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Newly diagnosed grade III or IV glioma including any of the following: Glioblastoma Anaplastic astrocytoma Gliosarcoma Anaplastic oligodendroglioma Anaplastic oligoastrocytoma Measurable or nonmeasurable disease No more than 5 weeks since prior brain surgery Recovered from surgery, post- operative infection, and other complications Preoperatively and postoperatively diagnostic contrast-enhanced MRI or CT scan of the brain performed prior to radiation therapy Patients diagnosed by stereotactic biopsy do not require the postoperative scan PATIENT CHARACTERISTICS: Karnofsky performance status ≥ 60% Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Serum creatinine ≤ 1.5 times upper limit of normal (ULN) Total bilirubin ≤ 2.0 mg/dL AST ≤ 4.0 times ULN No prolonged QT interval > 460 milliseconds on baseline electrocardiogram in the presence of normal serum potassium and magnesium No uncontrolled electrolyte imbalance (i.e., sodium < 132 mmol/L, potassium < 3.5 mEq/dL, magnesium < 1.7 mg/dL) No history of torsades de pointes type of ventricular arrhythmia Negative pregnancy test Not pregnant or nursing Fertile patients must use effective contraception No medical or psychiatric illness that, in the investigator's opinion, could potentially preclude the completion of study therapy No HIV positivity No active connective tissue disorders (e.g., lupus or scleroderma) that, in the investigator's opinion, may put the patient at high risk for radiation toxicity PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior brain radiotherapy or chemotherapy for brain tumor Concurrent corticosteroids to control cerebral edema allowed provided dose is stable or decreasing for the past 5 days No concurrent or plan to receive drugs that are known to prolong the QT interval No prior radiation to the head or neck (except for T1 glottic cancer) resulting in overlap of radiation fields

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: arsenic trioxide|nan|
|Drug: temozolomide|nan|
|Procedure: adjuvant therapy|nan|
|Radiation: intensity-modulated radiation therapy|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of arsenic trioxide |  |  | 
| Dose-limiting toxicities as measured by CTCAE version 3.0 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult glioblastoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult gliosarcoma, adult mixed glioma