Temozolomide and Radiation Therapy in Treating Patients With Gliomas

Radiation Therapy Oncology Group

Status and phase

Completed

Phase 2

Conditions

Brain and Central Nervous System Tumors

Treatments

Radiation: Radiation therapy

Drug: Temozolomide

Study type

Interventional

Funder types

Other

NETWORK

NIH

Identifiers

NCT00114140

NCI-2009-00723 (Registry Identifier)

RTOG 0424

CDR0000434849

Details and patient eligibility

About

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.

Full 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, one hour before RT weekdays, in the evening weekends. 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 at baseline, 6 months, 12 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.

Enrollment

136 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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
World Health Organization (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 non-supratentorial 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