Temozolomide and Radiation Therapy in Treating Patients With Gliomas

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
NRG Oncology Foundation, Inc.
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00114140
First received: June 13, 2005
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving temozolomide together with radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving temozolomide together with radiation therapy works in treating patients with low-grade gliomas.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: temozolomide
Procedure: adjuvant therapy
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of a Temozolomide-Based Chemoradiotherapy Regimen for High-Risk Low-Grade Gliomas

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Overall survival at 3 years. [ Time Frame: Death of last follow-up. Analysis occurs after all patients have been potentially followed for 3 years ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: From randomization to date of progression, death or last follow-up. Analysis occurs at the same time as the primary analysis. ] [ Designated as safety issue: No ]
  • Association of survival and progression-free survival with MGMT methylation status [ Time Frame: from randomization to date of progression, death or last follow-up. Analysis occurs after the primary outcome analysis. ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: From registration to one year. ] [ Designated as safety issue: No ]
  • Neurocognitive function [ Time Frame: From registration to one year. ] [ Designated as safety issue: No ]

Enrollment: 136
Study Start Date: January 2005
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Daily temozolomide, radiation therapy, temozolomide
Daily temozolomide plus concurrent radiotherapy (54 Gy/30 fractions/6 weeks) followed by temozolomide x 12 cycles
Drug: temozolomide Procedure: adjuvant therapy Radiation: radiation therapy

Detailed Description:

OBJECTIVES:

  • Compare the 3-year survival of patients with high-risk low-grade gliomas treated with temozolomide and radiotherapy followed by temozolomide alone with that of patients enrolled on European Organization for Research and Treatment of Cancer (EORTC)clinical trials EORTC-22844 and EORTC-22845.
  • Determine the toxicity of this regimen in these patients.
  • Determine the association between progression-free survival and O6-methylguanine-DNA methyltransferase (MGMT) methylation status in patients treated with this regimen.
  • Determine the association between survival and MGMT methylation status in patients treated with this regimen.
  • Determine the quality of life (QOL) of patients treated with this regimen.
  • Determine the neurocognitive function of patients treated with this regimen.
  • Evaluate the feasibility of collecting patient-reported QOL and neurocognitive assessments over 3 years.

OUTLINE: This is a non-randomized, multicenter study.

Patients receive oral temozolomide once daily on days 1-42 and undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Beginning 28 days after completion of chemoradiotherapy, patients receive oral temozolomide once daily on days 1-5. Treatment with temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed periodically for up to 36 months.

After completion of study treatment, patients are followed at 4 months, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 135 patients will be accrued for this study within 44 months.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed* supratentorial glioma of 1 of the following histologies:

    • Astrocytoma (diffuse fibrillary, protoplasmic, or gemistocytic)
    • Oligodendroglioma
    • Oligoastrocytoma NOTE: *Histologic atypia allowed provided no other histologic features (i.e., frequent mitoses, endothelial proliferation, and/or acute necrosis) that would result in a designation of anaplastic astrocytoma, anaplastic mixed oligodendroglioma or oligoastrocytoma, or glioblastoma multiforme are present
  • Unifocal or multifocal disease
  • WHO grade II disease
  • Neurofibromatosis allowed
  • Surgical biopsy or resection for tumor tissue sampling required within the past 12 weeks

    • Tissue block or core biopsy available for O6-methylguanine-DNA methyltransferase analysis and tissue banking
    • Patients who have only had a stereotactic biopsy are not eligible
  • Must have ≥ 3 of the following risk factors:

    • Age 40 and over
    • Largest preoperative tumor diameter ≥ 6 cm
    • Tumor crosses the midline
    • Astrocytoma-dominant tumor subtype
    • Preoperative Neurological Function Status > 1
  • No other low-grade glioma histologies, including any of the following:

    • Pilocytic astrocytoma
    • Subependymal giant cell astrocytoma of tuberous sclerosis
    • Subependymoma
    • Pleomorphic xanthoastrocytoma
    • Presence of a neuronal element, such as ganglioglioma
    • Dysneuroembryoplastic epithelial tumor
  • No high-grade glioma, including any of the following:

    • Anaplastic astrocytoma
    • Glioblastoma multiforme
    • Anaplastic oligodendroglioma
    • Anaplastic oligoastrocytoma
  • No tumors in any nonsupratentorial location, including any of the following:

    • Optic chiasm
    • Optic nerve(s)
    • Pons
    • Medulla
    • Cerebellum
    • Spinal cord
  • No evidence of disease progression to spinal meninges or noncontiguous cranial meninges (i.e., leptomeningeal gliomatosis) by MRI of the spine or cerebrospinal fluid (CSF) cytology

    • MRI of the spine or CSF cytology are not required for patients without symptoms of spinal/cranial meningeal disease progression

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic

  • Total bilirubin ≤ 1.5 mg/dL
  • Serum glutamate oxaloacetate transaminase (SGOT) or Serum glutamate pyruvate transaminase (SGPT) ≤ 2 times normal
  • Alkaline phosphatase ≤ 2 times normal

Renal

  • Serum creatinine ≤ 1.5 mg/dL

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No known HIV positivity
  • No other malignancy within the past 5 years except carcinoma in situ of the cervix or nonmelanoma skin cancer
  • No active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent immunotherapy or biologic therapy

Chemotherapy

  • No prior chemotherapy
  • No other concurrent chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy to the head and neck unless head and neck radiotherapy clearly excluded the brain (e.g., localized radiotherapy to the vocal cords)
  • No prior radiotherapy to the brain
  • No concurrent intensity modulated radiotherapy
  • No concurrent stereotactic boost radiotherapy

Surgery

  • See Disease Characteristics

Other

  • No other concurrent investigational agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00114140

  Show 47 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
NRG Oncology Foundation, Inc.
Investigators
Principal Investigator: Barbara J. Fisher, MD London Regional Cancer Program at London Health Sciences Centre
Study Chair: David R. Macdonald, MD, FRCPC London Regional Cancer Program at London Health Sciences Centre
Study Chair: Glenn J. Lesser, MD Comprehensive Cancer Center of Wake Forest University
Study Chair: Stephen W. Coons, MD St. Joseph's Hospital and Medical Center, Phoenix
  More Information

Additional Information:
No publications provided

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00114140     History of Changes
Other Study ID Numbers: RTOG 0424, CDR0000434849, NCI-2009-00723
Study First Received: June 13, 2005
Last Updated: July 10, 2014
Health Authority: United States: Federal Government

Keywords provided by Radiation Therapy Oncology Group:
adult diffuse astrocytoma
adult oligodendroglioma
adult mixed glioma

Additional relevant MeSH terms:
Glioma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 18, 2014