Temozolomide and Radiation Therapy in Treating Patients With Gliomas - Full Text View

Sponsor:	Radiation Therapy Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00114140

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 II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase II Study of a Temozolomide-Based Chemoradiotherapy Regimen for High-Risk Low-Grade Gliomas

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Temozolomide

U.S. FDA Resources

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

Primary Outcome Measures:

Overall survival at 3 years [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]
Toxicity rate [ Designated as safety issue: Yes ]
Association of survival and progression-free survival with MGMT methylation status [ Designated as safety issue: No ]
Quality of life [ Designated as safety issue: No ]
Neurocognitive function [ Designated as safety issue: No ]

Estimated Enrollment:	135
Study Start Date:	January 2005
Estimated Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

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 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
SGOT or 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

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

Show 47 Study Locations

Sponsors and Collaborators

Radiation Therapy Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Barbara J. Fisher, MD	London Regional Cancer Program at London Health Sciences Centre
Investigator:	David R. Macdonald, MD, FRCPC	London Regional Cancer Program at London Health Sciences Centre
Investigator:	Glenn J. Lesser, MD	Wake Forest University
Investigator:	Stephen W. Coons, MD	St. Joseph's Hospital and Medical Center, Phoenix

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Radiation Therapy Oncology Group ( Walter John Curran, Jr )
Study ID Numbers:	CDR0000434849, RTOG-0424
Study First Received:	June 13, 2005
Last Updated:	August 27, 2009
ClinicalTrials.gov Identifier:	NCT00114140 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adult diffuse astrocytoma
adult oligodendroglioma
adult mixed glioma

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Nervous System Diseases
Central Nervous System Neoplasms
Temozolomide
Pharmacologic Actions
Neuroectodermal Tumors
Neoplasms

Neoplasms by Site
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Antineoplastic Agents, Alkylating
Glioma
Neoplasms, Neuroepithelial
Alkylating Agents
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 27, 2009