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Radiation Therapy, Arsenic Trioxide, and Temozolomide in Treating Patients With Newly Diagnosed High-Grade Glioma
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), June 2009
First Received: July 19, 2008   Last Updated: June 23, 2009   History of Changes
Sponsors and Collaborators: Beckman Research Institute
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00720564
  Purpose

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 Intervention Phase
Brain and Central Nervous System Tumors
Drug: arsenic trioxide
Drug: temozolomide
Procedure: adjuvant therapy
Radiation: intensity-modulated radiation therapy
Radiation: radiation therapy
Phase I

Study Type: Interventional
Study Design: 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)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose of arsenic trioxide [ Designated as safety issue: Yes ]
  • Dose-limiting toxicities as measured by CTCAE version 3.0 [ Designated as safety issue: Yes ]

Estimated Enrollment: 18
Study Start Date: April 2008
Estimated Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00720564

Locations
United States, California
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010-3000
Contact: Jana Portnow, MD     800-826-4673     JPortnow@coh.org    
Sponsors and Collaborators
Beckman Research Institute
Investigators
Principal Investigator: Jana Portnow, MD Beckman Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Comprehensive Cancer Center ( Jana Portnow )
Study ID Numbers: CDR0000600335, CHNMC-07058, CEPHALON-CHNMC-07058
Study First Received: July 19, 2008
Last Updated: June 23, 2009
ClinicalTrials.gov Identifier: NCT00720564     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
adult glioblastoma
adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult gliosarcoma
adult mixed glioma

Study placed in the following topic categories:
Glioblastoma
Astrocytoma
Adjuvants, Immunologic
Arsenic trioxide
Central Nervous System Neoplasms
Temozolomide
Oligodendroglioma
Glioma
Glioblastoma Multiforme
Antineoplastic Agents, Alkylating
Gliosarcoma
Alkylating Agents
Nervous System Neoplasms

Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Nervous System Diseases
Arsenic trioxide
Central Nervous System Neoplasms
Temozolomide
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Nervous System Neoplasms

ClinicalTrials.gov processed this record on September 09, 2009