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

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)

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.

Study Overview

• Status: Completed
• Conditions: Brain and Central Nervous System Tumors
• Intervention / Treatment: Drug: arsenic trioxide; Radiation: radiation therapy; Drug: temozolomide; Procedure: adjuvant therapy; Radiation: intensity-modulated radiation therapy

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 Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: July 19, 2008
• First Submitted That Met QC Criteria: July 19, 2008
• First Posted (Estimate): July 22, 2008

Study Record Updates

• Last Update Posted (Estimate): August 11, 2010
• Last Update Submitted That Met QC Criteria: August 9, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: adult glioblastoma; adult gliosarcoma; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma; adult mixed glioma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms; Neoplasms by Site; Nervous System Neoplasms; Central Nervous System Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide; Arsenic Trioxide
• Other Study ID Numbers: CDR0000600335; P30CA033572 (U.S. NIH Grant/Contract); CHNMC-07058; CEPHALON-CHNMC-07058