Vorinostat, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

Inclusion Criteria:

* PRE-REGISTRATION:
* Central pathology review submission; this review is mandatory prior to registration to confirm eligibility; it should be initiated as soon after surgery as possible
* Treatment should begin \>= 2 weeks and =\< 5 weeks following surgery
* REGISTRATION:
* Histologically confirmed glioblastoma multiforme as determined by pre-registration central pathology review; Note: gliosarcomas and other grade 4 astrocytoma variants (e.g., giant cell) are eligible
* Measurable or evaluable disease by gadolinium magnetic resonance imaging (MRI) or contrast computed tomography (CT) scan; Note: patients who have had a gross total resection (GTR) are eligible on the basis of evaluable disease

  * Must begin partial brain radiotherapy on the same day that vorinostat and temozolomide begin
* Karnofsky performance status of \>= 60
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* White blood cell (WBC) \>= 3,000/mm\^3
* Hemoglobin \>= 10.0 g/dL; Note: this level may be reached by transfusion
* Total bilirubin =\< 2.0 x institutional upper limit of normal (ULN)
* Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) =\< 2.0 x ULN
* Creatinine =\< 1.5 mg/dL
* Life expectancy \>= 12 weeks
* Negative serum pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
* For Phase I established MTD and Phase II patients only: Willing and able to complete neurocognitive testing
* Ability to provide informed written consent
* Willing to return to Alliance or Adult Brain Tumor Consortium (ABTC) enrolling institution for follow-up
* Phase I established MTD patients and Phase II patients: Willing to provide mandatory tissue samples (slides or blocks) for research purposes
* Willing to forego other cytotoxic and non-cytotoxic drug therapy against the tumor while being treated with vorinostat and temozolomide

Exclusion Criteria:

* Any of the following:

  * Pregnant women
  * Nursing women
  * Men or women of childbearing potential who are unwilling to employ adequate contraception throughout the duration of the study and for 12 weeks after treatment has ended
* Prior cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy for brain tumors
* Prior cranial RT
* Prior Gliadel wafers
* Known hypersensitivity to any of the components of vorinostat or other agents used in study
* Valproic acid, another histone deacetylase inhibitor, =\< 2 weeks prior to registration and during treatment
* Other active malignancy =\< 3 years prior to registration; Exception: non-melanotic skin cancer or carcinoma in situ of the cervix; Note: if there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer
* Uncontrolled infection
* Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; Note: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
* Co-morbid systemic illness or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with proper assessment of safety and adverse events of the prescribed regimens
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
* History of myocardial infarction or unstable angina =\< 6 months prior to registration or congestive heart failure (CHF) requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
* New York Heart Association (NYHA) \>= Class II Congestive Heart Failure
* Inability to take oral medications
* Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
* Congenital long QT syndrome
* Prolonged corrected (QTc) interval (\> 450 msec)
* Any of the following Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes =\< 7 days prior to registration

  * Quinidine, procainamide, disopyramide
  * Amiodarone, sotalol, ibutilide, dofetilide
  * Erythromycin, clarithromycin
  * Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
  * Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine