Radiation Therapy or Radiation Therapy and Temozolomide or Temozolomide Alone in Treating Patients With Newly Diagnosed Anaplastic Glioma

• Overall survival [ Designated as safety issue: No ]
  
• Time to event (i.e., clinical progression, neurocognitive progression, and radiographic progression) [ Designated as safety issue: No ]
  

• Progression-free survival at 6, 12, and 24 months [ Designated as safety issue: No ]
  
• Objective tumor response [ Designated as safety issue: No ]
  
• Treatment-related adverse events according to NCI CTCAE v.3 [ Designated as safety issue: Yes ]
  
• Interphase fusion of the CEP1 probe and a 19p12 probe to detect the t(1:19) in paraffin-embedded tumor sections by FISH [ Designated as safety issue: No ]
  
• Associations between clinical outcomes (survival, progression-free survival, and objective response) and MGMT methylation status [ Designated as safety issue: No ]
  
• Additional known prognostic markers including, but not limited to, PTEN, EGFR, EGFRvIII, p53, and any additional markers which are known or are identified during the course of this study that are considered relevant by the study investigators and the ... [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine whether there is a survival advantage for patients with newly diagnosed 1p/19q codeleted anaplastic glioma who receive concurrent temozolomide and radiotherapy (RT) followed by adjuvant temozolomide over that observed in patients treated with RT alone (control).

Secondary

• Determine whether there is a neurocognitive advantage in patients who receive temozolomide alone (Arm III) vs temozolomide with concurrent RT (Arm II) over that observed in patients treated with RT alone (Arm I).
• Determine whether there is a difference in survival based on t(1;19)(q10,p10) translocation status and MGMT promoter hypermethylation status in these patients.
• Perform descriptive comparisons of additional secondary outcome endpoints, including time to progression, progression free survival, and the proportion of patients free of progression at 6, 12, and 24 months.
• Determine the toxicity of RT and concurrent/adjuvant temozolomide in these patients.
• Determine descriptively whether it is reasonable to delay RT by documenting the time to progression and progression-free survival of patients receiving temozolomide alone.
• Determine the quality of life and neurocognitive effects in patients treated on this protocol and correlate these results with outcome endpoints.
• Bank blood products (i.e., plasma, DNA, and buffy coat) and tumor tissue for future scientific investigations.

OUTLINE: This is a multicenter study. Patients are stratified according to cooperative group (EORTC vs North American groups [NCCTG, RTOG, CTSU, and NCIC CTG]), age (≤ 50 years vs > 50 years), and ECOG performance status (0-1 vs 2). Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients undergo radiotherapy (RT) 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients undergo RT as in arm I and receive oral temozolomide once daily on days 1-7 for 6 weeks. Beginning 4 weeks after completion of concurrent chemoradiotherapy, patients receive adjuvant oral temozolomide once daily days 1-5. Treatment with adjuvant temozolomide repeats every 28 days for 6-12 courses in the absence of disease progression and unacceptable toxicity.
• Arm III: Patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Patients complete neurocognitive questionnaires (i.e., the Hopkins Verbal Learning test, the Controlled Oral Word Association test from the Multilingual Aphasia Examination, General Mental Ability: Trail Making tests A and B, and the Recall and Recognition of Word List encoded from the HVLT-R test) and quality of life questionnaires (i.e., EORTC QOL-C30 and QOL-BN20) at baseline and periodically during study therapy.

Tumor tissue samples are collected during surgery and analyzed by FISH to detect t(1:19), and for MGMT gene promoter hypermethylation status and additional known prognostic markers, including but not limited to PTEN, EGFR, EGFRvIII, and p53.

After completion of study therapy, patients are followed periodically.