Radiation Therapy With or Without Temozolomide in Treating Patients With Low-Grade Glioma
Radiation Therapy With or Without Temozolomide in Treating Patients With Low-Grade Glioma
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized
 radiation therapy that delivers a high dose of radiation directly to the tumor may kill more
 tumor cells and cause less damage to normal tissue. 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. It is not yet known whether radiation therapy is
 more effective when given together with or without temozolomide in treating patients with
 low-grade glioma.

 PURPOSE: This randomized phase III trial is studying radiation therapy so see how well it
 works when given together with or without temozolomide in treating patients with low-grade
 glioma.
OBJECTIVES:

 Primary

 -  To determine whether the addition of temozolomide to fractionated radiotherapy improves
 the progression-free survival (PFS) of patients with symptomatic or progressive
 low-grade gliomas.

 -  To determine whether the addition of temozolomide to fractionated radiotherapy improves
 the median overall survival (OS) of these patients.

 Secondary

 -  To determine whether combination therapy with temozolomide and radiotherapy improves or
 maintains cognition and quality of life compared to radiotherapy alone.

 -  To compare the toxicities (severe or worse [≥ grade 3]) of radiotherapy with vs without
 temozolomide in these patients.

 -  To assess the impact of the presence or absence of 1p and 19q deletion on PFS and OS.

 -  To determine the impact of 1p and 19q status on PFS and OS of patients treated with
 temozolomide.

 -  To create a tumor and tissue bank, including plasma and germ line DNA, within the ECOG
 Pathology Coordinating Office.

 OUTLINE: This is a multicenter study. Patients are stratified according to age (< 40 years vs
 ≥ 40 years), 1p and 19q status (both deleted vs either/both intact vs undeterminable),
 pre-operative maximum tumor diameter (< 6 cm vs ≥ 6 cm [based on T2 or FLAIR MRI]), Karnofsky
 performance status (60-70% vs 80-100%), and contrast enhancement on pre-treatment MRI scan
 (present vs absent). Patients are randomized to 1 of 2 treatment arms.

 -  Arm I: Patients undergo 3-dimensional conformal or intensity-modulated radiotherapy once
 daily 5 days a week for 5½ weeks (28 fractions).

 -  Arm II: Patients undergo radiotherapy as in arm I and receive concurrent oral
 temozolomide once daily for 5½ weeks. Beginning 28 days after completion of
 chemoradiotherapy, patients receive oral temozolomide alone once daily on days 1-5.
 Treatment with temozolomide repeats every 28 days for 12 courses in the absence of
 disease progression or unacceptable toxicity.

 Some patients undergo quality-of-life and neurocognitive (e.g., visual scanning speed,
 divided attention, language, memory, and fine motor skills) assessments at baseline, annually
 until disease progression, and at the time of disease progression.

 Tumor tissue samples are collected at baseline for confirmation of diagnosis and
 determination of 1p and 19q deletion status. Peripheral blood, serum, and additional tumor
 tissue samples may be collected for further research studies.

 After completion of study treatment, patients are followed up periodically for up to 15
 years.
DISEASE CHARACTERISTICS:

 -  Histologically confirmed* supratentorial low-grade glioma, including 1 of the
 following:

 -  Grade 2 astrocytoma

 -  Grade 2 oligodendroglioma

 -  Grade 2 oligoastrocytoma (mixed glioma containing astrocytoma and
 oligodendroglioma)

 -  NOTE: *If the pathology from multiple procedures supports the diagnosis of a brain
 tumor, the qualifying pathology of grade 2 astrocytoma, oligodendroglioma, or
 oligoastrocytoma must be the most recent pathological diagnosis; no pathological
 diagnosis of grade 3 or 4 glioma at any time

 -  Paraffin-embedded tumor specimen available for submission for confirmation of
 pathological review and determination of 1p and 19q deletion status

 -  Patients must currently meet ≥ 1 of the following criteria*:

 -  Uncontrolled symptoms, defined as any of the following:

 -  Headaches associated with mass effect

 -  Uncontrolled seizures despite two different antiepileptic drug regimens
 (i.e., two antiepileptic drugs tested either sequentially or in combination)

 -  Focal neurological symptoms

 -  Cognitive symptoms or deficits

 -  Tumor progression by serial MRIs, defined as any of the following:

 -  New or progressive enhancement

 -  New or progressive T2 or FLAIR signal abnormality

 -  Age ≥ 40 years

 -  NOTE: *Patients < 40 years of age whose only symptom of low-grade glioma is seizures
 that are well-controlled on antiepileptic drugs AND who have no evidence of
 radiographic progression are not eligible.

 -  Patients who have undergone gross total resection and have no detectable residual
 disease are eligible

 -  No pilocytic astrocytoma, ganglioglioma, pleomorphic xanthoastrocytoma, or
 dysembryoplastic neuroepithelial tumors

 PATIENT CHARACTERISTICS:

 -  Karnofsky performance status 60-100%

 -  WBC ≥ 3,000/mm^3

 -  ANC ≥ 1,500/mm^3

 -  Platelet count ≥ 100,000/mm^3

 -  Hematocrit ≥ 30%

 -  Bilirubin ≤ 2 times upper limit of normal (ULN)

 -  AST and ALT ≤ 3 times ULN

 -  Creatinine ≤ 2.0 times ULN

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  Able to undergo MRI with and without contrast

 -  No other malignancy within the past 5 years, except for nonmelanoma skin cancer or
 cervical carcinoma in situ

 -  No uncontrolled infection

 -  No known HIV positivity

 -  No medical disorder that would increase risks associated with radiotherapy and
 temozolomide

 -  No other disorder that would limit life expectancy to < 5 years

 PRIOR CONCURRENT THERAPY:

 -  No prior radiotherapy, cytotoxic chemotherapy, radiosurgery, or investigational
 therapy directed at the brain tumor

 -  Any number of prior surgical procedures for the brain tumor allowed

 -  No prior radiotherapy to the head unless the radiotherapy ports entirely excluded the
 brain

 -  At least 2 weeks since any prior brain surgery (e.g., stereotatic biopsy, open biopsy,
 or resection)

 -  At least 6 weeks since prior MRI and chest x-ray

 -  If resection is performed, an MRI after surgery is required