Proton Beam or Intensity-Modulated Radiation Therapy in Preserving Brain Function in Patients With IDH Mutant Grade II or III Glioma

Inclusion Criteria:

• PRIOR TO STEP 1 REGISTRATION

• Tumor tissue must be available for submission for central pathology review

• Grade II and III gliomas IDH mutant gliomas including; diffuse astrocytoma,anaplastic astrocytoma, oligodendroglioma, anaplastic oligodendroglioma,oligoastrocytoma, anaplastic oligoastrocytoma

• Documentation from the enrolling site confirming the presence of IDH mutation and 1p/19q status; the provided information must document assays performed in clinicallaboratory improvement amendments (CLIA)-approved laboratories and be uploaded priorto Step 2 registration

• Age >= 18

• The trial is open to both genders

• Only English or French speaking patients are eligible to participate as thecognitive assessments are only available in these languages

• The patient or a legally authorized representative must provide study-specificinformed consent prior to study entry

• History and physical exam, and Karnofsky performance status of >= 70 within 30 daysprior to registration

• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (within 60 days prior toregistration)

• Platelets >= 100,000 cells/mm^3 (within 60 days prior to registration)

• Hemoglobin >= 10.0 g/dl (Note: the use of transfusion or other intervention toachieve hemoglobin [Hgb] >= 10.0 g/dl is acceptable) (within 60 days prior toregistration)

• Bilirubin =< 1.5 upper limit of normal (ULN) (within 60 days prior to registration)

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN (within 60 days prior to registration)

• Blood urea nitrogen (BUN) < 30 mg/dl (within 60 days prior to registration)

• Serum creatinine < 1.5 mg/dl (within 60 days prior to registration)

• Pre-operative MRI imaging of the brain available for radiation planning

• Post-operative MRI imaging with contrast is mandatory obtained for radiation therapyplanning; enrolling sites are not mandated although highly encouraged to obtainthin-slice (< 1.5 mm) 3 dimensional (D) pre and post contrast and axial T2/FLAIRsequences for planning purposes

• Patients must be able to swallow capsules

• PRIOR TO STEP 2 REGISTRATION

• Histologically proven diagnosis of supratentorial, World Health Organization (WHO)grade II or III astrocytoma, oligodendroglioma or oligoastrocytoma, with IDHmutation confirmed by central review

• The following baseline neurocognitive assessments must be completed and uploadedprior to Step 2 registration: HVLT-R (recall, delayed recall, and recognition), TMTParts A and B, and COWA; the neurocognitive assessment will be uploaded into afolder in the NRG Medidata RAVE System for central evaluation; once the upload andscoring of the tools are complete, a notification will be sent within 3 businessdays to the Research Associate (RA) to proceed to Step 2; in order for the patientto be eligible, at least 5 of the 6 neurocognitive assessments must be able to bescored (i.e. free of any errors)

• Completion of all items on the following baseline quality of life forms: MDASI-BT,LASA QOL, WPAI-GH and Employment Questionnaire; these quality of life forms will berequired and data entered at step 2 registration

• Financial clearance for proton therapy treatment prior step 2 registration

• Women of childbearing age must have a negative serum pregnancy test within 14 daysprior to step 2 registration

Exclusion Criteria:

• Definitive clinical or radiologic evidence of metastatic disease; if applicable

• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease freefor a minimum of 3 years; (for example, carcinoma in situ of the breast, oral cavityor cervix are permissible)

• Prior cranial radiotherapy or radiotherapy to the head and neck where potentialfield overlaps would exist

• Prior chemotherapy or radiotherapy for any brain tumor

• Histologic diagnosis of glioblastoma (WHO grade IV) or pilocytic astrocytoma (WHOgrade I)

• Definitive evidence of multifocal disease

• Planned use of cytotoxic chemotherapy during radiation (only adjuvant temozolomidetherapy will be used on this protocol)

• Patients with infra-tentorial tumors are not eligible

• Prior history of neurologic or psychiatric disease believed to impact cognitivefunction

• The use of memantine during or following radiation is NOT allowed

• Severe, active co-morbidity defined as follows:

• Unstable angina or congestive heart failure requiring hospitalization within 6months prior to enrollment

• Transmural myocardial infarction within the last 6 months prior toregistration; evidence of recent myocardial infarction or ischemia by thefindings of S-T elevations of >= 2 mm using the analysis of anelectrocardiogram (EKG) performed within 28 days prior to registration (Note:EKG to be performed only if clinical suspicion of cardiac issue)

• New York Heart Association grade II or greater congestive heart failurerequiring hospitalization within 12 months prior to registration

• Serious and inadequately controlled arrhythmia at step 2 registration

• Serious or non-healing wound, ulcer or bone fracture or history of abdominalfistula, intra-abdominal abscess requiring major surgical procedure, openbiopsy or significant traumatic injury within 28 days prior to registration,with the exception of the craniotomy for surgical resection

• Acute bacterial or fungal infection requiring intravenous antibiotics at thetime of registration

• Hepatic insufficiency resulting in clinical jaundice and/or coagulationdefects; note, however, that laboratory tests for coagulation parameters arenot required for entry into this protocol

• Chronic obstructive pulmonary disease exacerbation or other respiratory illnessrequiring hospitalization or precluding study therapy at the time ofregistration

• Human immunodeficiency virus (HIV) positive with CD4 count < 200cells/microliter; acquired immune deficiency syndrome (AIDS) based upon currentCenters for Disease Control and Prevention (CDC) definition; note, however,that HIV testing is not required for entry into this protocol

• Any other severe immunocompromised condition

• Active connective tissue disorders, such as lupus or scleroderma, that in theopinion of the treating physician may put the patient at high risk forradiation toxicity

• End-stage renal disease (i.e., on dialysis or dialysis has been recommended)

• Any other major medical illnesses or psychiatric treatments that in theinvestigator's opinion will prevent administration or completion of protocoltherapy

• Inability to undergo MRI with and without contrast (e.g. claustrophobia, non-MRIcompatible implant or foreign body, gadolinium allergy or renal dysfunctionpreventing the patient from receiving gadolinium- institutional guidelines should beused to determine if patients are at risk for renal dysfunction); note that patientswith severe claustrophobia are permitted on this study if they are willing and ableto undergo MRI with adequate sedation or anesthesia

• Patients known to have hypersensitivity to dacarbazine (DTIC) are not eligible