This trial is active, not recruiting.

Condition brain and central nervous system tumors
Treatments temozolomide, adjuvant therapy, radiation therapy
Phase phase 2
Sponsor Radiation Therapy Oncology Group
Collaborator National Cancer Institute (NCI)
Start date January 2005
End date September 2016
Trial size 136 participants
Trial identifier NCT00114140, CDR0000434849, NCI-2009-00723, RTOG 0424


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Intervention model single group assignment
Masking open label
Primary purpose treatment
Daily temozolomide plus concurrent radiotherapy (54 Gy/30 fractions/6 weeks) followed by temozolomide x 12 cycles
adjuvant therapy
radiation therapy

Primary Outcomes

Overall survival at 3 years.
time frame: Death of last follow-up. Analysis occurs after all patients have been potentially followed for 3 years
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.
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.
Quality of life
time frame: From registration to one year.
Neurocognitive function
time frame: From registration to one year.

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title A Phase II Study of a Temozolomide-Based Chemoradiotherapy Regimen for High-Risk Low-Grade Gliomas
Principal investigator Barbara J. Fisher, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in November 2015.
Information provided to ClinicalTrials.gov by Radiation Therapy Oncology Group.