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

Brain and Central Nervous System Tumors Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00720564
• Other study ID #: CDR0000600335
• Secondary ID: P30CA033572CHNMC
• Status: Completed
• Phase: Phase 1
• First received: July 19, 2008
• Last updated: August 9, 2010
• Start date: April 2008
• Est. completion date: February 2009

Study information

• Verified date: August 2010
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: February 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Drug:
• arsenic trioxide

• temozolomide

Procedure:
• adjuvant therapy

Radiation:
• intensity-modulated radiation therapy

• radiation therapy

Locations

Country	Name	City	State
United States	City of Hope Comprehensive Cancer Center	Duarte	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of arsenic trioxide			Yes
Primary	Dose-limiting toxicities as measured by CTCAE version 3.0			Yes