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

Sponsor

City of Hope Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00720564

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

10.1

Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: arsenic trioxide Drug: temozolomide Procedure: adjuvant therapy Radiation: intensity-modulated radiation therapy Radiation: radiation therapy	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Primary Purpose:

Treatment

Official Title:

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)

Study Start Date :

Apr 1, 2008

Actual Primary Completion Date :

Feb 1, 2009

Actual Study Completion Date :

Feb 1, 2009

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of arsenic trioxide []
Dose-limiting toxicities as measured by CTCAE version 3.0 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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