Radiation Therapy or Radiation Therapy and Temozolomide in Treating Patients with Newly Diagnosed Anaplastic Glioma or Low Grade Glioma

Summary

Objectives

PRIMARY OBJECTIVES:
I. To determine whether patients who receive radiotherapy with concomitant temozolomide followed by adjuvant temozolomide (radiation therapy [RT] + temozolomide [TMZ] ? TMZ) (ARM B) have a marginally better progression free survival (PFS) as compared with patients who receive radiotherapy followed by adjuvant procarbazine hydrochloride, lomustine, vincristine sulfate (PCV) chemotherapy (RT ? PCV) (ARM A).

SECONDARY OBJECTIVES:
I. To determine whether patients who receive RT + TMZ ? TMZ have a longer time to progression (clinical or radiographic progression) as compared with patients who receive radiotherapy followed by adjuvant PCV chemotherapy (RT ? PCV).
II. To determine whether there is a difference in survival based on (1;19)(q10,p10) translocation status and MGMT promoter hypermethylation status.
III. To perform descriptive comparisons of additional secondary outcome endpoints, including overall survival, objective tumor response, prognostic factor analysis and quality of life, including comparisons between photon and proton radiotherapy.
IV. To determine the toxicity of the treatment in each arm and perform descriptive comparisons as well as comparisons between photon and proton radiotherapy.
V. To determine the neurocognitive and quality of life (QOL) effects in patients treated on this protocol and correlate these results with outcome endpoints as well as comparisons between photon and proton radiotherapy.
VI. To store biospecimens (plasma or serum, deoxyribonucleic acid [DNA] from tumor and peripheral blood mononuclear cells DNA, tumor tissue, and magnetic resonance imaging [MRI]/ computed tomography [CT] images) for future correlative scientific investigations which explore the scientific relationships of any known and yet-to-be developed markers to clinical outcome and imaging data.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients undergo 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) on days 1-5 for 5-7 weeks. Patients also receive procarbazine hydrochloride orally (PO) on days 8-21, lomustine PO on day 1 and vincristine sulfate intravenously (IV) on days 8 and 29 of courses 3-8. Treatment repeats every 6-7 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) scans throughout the trial as well as chest x-ray and collection of blood samples on trial.

ARM B: Patients undergo RT as in Arm A and receive temozolomide PO once daily (QD) on days 1-5 for 5-7 weeks. Beginning 4 weeks after completion of concurrent chemoradiotherapy, patients receive adjuvant temozolomide PO QD on days 1-5. Treatment with adjuvant temozolomide repeats every 4 weeks for 6-12 courses in the absence of disease progression and unacceptable toxicity. Patients also undergo CT or MRI scans throughout the trial and collection of blood samples on trial.

After completion of study therapy, patients are followed up every 12 weeks for 1 year, every 4 months for 2 years, and then every 6 months thereafter.