Randomized Phase II Trial of Hypofractionated Dose-Escalated Photon IMRT or Proton Beam Therapy Versus Conventional Photon Irradiation With Concomitant and Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma

• PRIOR TO STEP 1 REGISTRATION

• A diagnostic contrast-enhanced magnetic resonance imaging (MRI) (no other scan type allowed) of the brain must be performed postoperatively within 72 hours of resection; the enhancing tumor must have a maximal diameter of 5 cm; the tumor diameter will be the greatest diameter as measured on the contrast-enhanced postoperative MRI and will include residual disease and/or the postoperative surgical cavity as appropriate; for cases where residual disease or postoperative surgical cavity is NOT identifiable (e.g., polar glioblastomas [GBMs] where a polar lobectomy is performed), the patient will be excluded from the trial

• The GBM tumor must be located in the supratentorial compartment only (any component involving the brain stem or cerebellum is not allowed)

• Patients must provide study-specific informed consent prior to step 1 registration

• PRIOR TO STEP 2 REGISTRATION

• Histologically proven diagnosis of glioblastoma (World Health Organization [WHO] grade IV) confirmed by central review prior to step 2 registration

• Tumor tissue that is determined by central pathology review prior to step 2 registration to be of sufficient quantity for analysis of O6-methylguanin-DNA-methyltransferase (MGMT) status

• Patients must have at least 1 block of tumor tissue; submission of 2 blocks is strongly encouraged to maximize the chances of eligibility; at least 1 cubic centimeter of tissue composed primarily of tumor must be present

• Diagnosis must be made by surgical excision, either partial or complete; stereotactic biopsy or cavitron ultrasonic suction aspirator (CUSA) technique are not allowed

• History/physical examination within 28 days prior to step 2 registration

• The patient must have recovered from effects of surgery, postoperative infection, and other complications within 28 days prior to step 2 registration

• Documentation of steroid doses within 28 days prior to step 2 registration

• Karnofsky performance status >= 70 within 28 days prior to step 2 registration

• Age >= 18

• Absolute neutrophil count (ANC) >= 1,800 cells/mm^3

• Platelets >= 100,000 cells/mm^3

• Hemoglobin >= 10.0 g/dl (note: the use of transfusion or other intervention to achieve hemoglobin (Hgb) >= 10.0 g/dl is acceptable)

• Bilirubin =< 1.5 upper limit of normal (ULN)

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN

• Negative serum pregnancy test obtained for females of child-bearing potential within 28 days prior to step 2 registration