Radiation Therapy With Concomitant and Adjuvant Temozolomide Versus Radiation Therapy With Adjuvant PCV Chemotherapy in Patients With Anaplastic Glioma or Low Grade Glioma

Pre-Registration Inclusion Criteria:

• United States (US) and Canadian sites:

• This review is mandatory prior to registration to confirm eligibility; patientsmust be willing to submit tissue samples for mandatory central pathology reviewsubmission; it should be initiated as soon after surgery as possible

• Tissue must have been determined to have local 1p/9q co-deletion and IDH mutationprior to submission for central path review

• Tumor tissue must show co-deletion of chromosomes 1p and 19q; for eligibility,the 1p/19q analysis results will be accepted from the local site, as determinedby either a locally available or reference laboratory (for US, must be ClinicalLaboratory Improvement Act [CLIA] certified); acceptable methods fordetermination of 1p/19q loss include fluorescent in-situ hybridization (FISH),by genomic sequencing or methylomic analyses; US and Canadian sites must send acopy of the official report to the pathology coordinator and quality assurancespecialist (QAS)

• Tumor must also show evidence of IDH mutation by immunohistochemistry orgenomic analyses; this should be performed at the local site (US: performed ina CLIA certified laboratory); the site must send a copy of the official reportto the pathology coordinator and QAS

Registration Inclusion Criteria:

• Newly diagnosed and =< 3 months from surgical diagnosis; patients are also eligibleif they have had a prior surgical procedure > 3 months earlier for low grade glioma,as long as the patient has not received prior radiation or prior chemotherapy

• Histological evidence of World Health Organization (WHO) grade III anaplastic gliomaor WHO grade II low grade glioma with locally diagnosed combined 1p/19q loss and thepresence of an either IDH1 or IDH2, both as established by a local or referencedlaboratory qualified for the study

• Note: mixed gliomas are eligible, regardless of the degree of astrocytic oroligodendrocytic predominance, as long as the tumor is also co-deleted for 1p and 19q

• Patients with codeleted low grade gliomas must also be considered "high risk" byexhibiting one or more of the following characteristics:

• Age >= 40 and any surgical therapy

• Age < 40 with prior and subtotal resection or biopsy (i.e., anything less thangross total resection)

• Documented growth following prior surgery (NOTE: patients with prior surgerycannot have received prior radiation, chemotherapy or targeted therapy)

• Intractable seizures

• Surgery (partial or gross total resection or biopsy) must be performed >= 2 weeksprior to registration; patient must have recovered adequately from the effects ofsurgery

• Absolute neutrophil count (ANC) >= 1,500/mm^3 obtained =< 21 days prior toregistration

• Platelet (PLTs) count >= 100,000/mm^3 obtained =< 21 days prior to registration

• Hemoglobin (Hgb) > 9.0 g/dL obtained =< 21 days prior to registration

• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) obtained =< 21days prior to registration

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x ULN obtained =< 21 days prior to registration

• Creatinine =< 1.5 x ULN obtained =< 21 days prior to registration

• Negative serum or urine pregnancy test done =< 7 days prior to registration, forwomen of childbearing potential only

• Willingness and ability to personally complete neurocognitive testing (withoutassistance) and willingness to complete the QOL testing, (either personally or withassistance)

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2

• Written informed consent

• Willingness to return to enrolling institution for follow-up during the activemonitoring phase (that is, the active treatment and observation portion) of thestudy); patients who have been formally transferred to another active and approvedsite participating in this study would not need to return to the enrollinginstitution for this purpose

• Willingness to allow the provision of tissue samples for correlative research, aslong as adequate tissues are available; patients will not be excluded fromparticipation in the study, if they are willing to allow provision of tissues forthe correlative research, but there are insufficient quantities of tissue for thecorrelative analyses (e.g., a patient otherwise eligible and willing who had biopsyonly) Willingness to allow the provision of blood samples for correlative research;patients are not excluded from participation in the study, if they are willing toprovide the mandatory biospecimens for translational/correlative research, but forlogistical reasons the specimens(s) were not obtainable or if the volume collectedwas insufficient

Registration Exclusion Criteria:

• The following categories are ineligible:

• Pregnant women

• Nursing women

• Men or women of childbearing potential who are unwilling to employ adequatecontraception or contraceptive method during this study and 6 months followingthe completion of chemotherapy treatments

• History of prior radiation therapy or chemotherapy for glioma; note: patients whohave a history of prior low grade glioma (with or without a distant history of priorsurgery for that glioma), but who have never received prior chemotherapy orradiation therapy for the glioma are eligible for the study

• Co-morbid systemic illnesses or other severe concurrent disease which, in thejudgment of the investigator, would make the patient inappropriate for entry intothis study or interfere significantly with the proper assessment of safety andtoxicity of the prescribed regimens

• Concomitant serious immunocompromised status (other than that related to concomitantsteroids) that would compromise the safety of the patient on the study

• Patients known to be human immunodeficiency virus (HIV) positive and currentlyreceiving retroviral therapy are not eligible; note: patients known to be HIVpositive, but without clinical evidence of an immunocompromised state, are eligiblefor the study

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliancewith study requirements

• Receiving any other investigational agent that would be considered as a treatmentfor the primary neoplasm

• Other active malignancy within 5 years of registration; exceptions: non-melanoticskin cancer or carcinoma-in-situ of the cervix; note: if there is a history of priormalignancy, the patient is not eligible if they are receiving other specifictreatment (with the exclusion of hormonal therapy or Her-2 inhibitors) for theircancer or if they have received prior total body irradiation which included thebrain

• History of myocardial infarction =< 6 months, or congestive heart failure requiringuse of ongoing maintenance therapy for life-threatening ventricular arrhythmias

• Recent history of hepatitis infection or if the treating physician determined thatthe patient would be at significant risk of reactivation of hepatitis