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