Adavosertib, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed or Recurrent Glioblastoma

Inclusion Criteria:

* Patients must have a tumor tissue form indicating availability of archived tissue from initial resection at diagnosis of glioblastoma completed and signed by a pathologist
* Patients must have a Karnofsky performance status \>= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
* Absolute neutrophil count \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Hemoglobin \>= 9 g/dL
* Total bilirubin =\< institutional upper limit of normal
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional upper limit of normal; if above the institutional upper limit of normal but =\< 3 times institutional upper limit of normal, the decision to initiate temozolomide treatment should carefully consider the benefits and risks for the individual patient
* Creatinine =\< institutional upper limit of normal OR creatinine clearance \>= 60 ml/min/1.73 m\^2 for patients with creatinine levels above institutional normal
* Activated partial thromboplastin time (APTT)/partial thromboplastin time (PTT) =\< 1.5 x institutional upper limit of normal
* Patients must be able to provide written informed consent
* Patients must have magnetic resonance imaging (MRI) within 21 days of starting treatment
* Women of childbearing potential must have a negative serum pregnancy test prior to study entry; women of childbearing potential and men must agree to use two birth control methods (either two barrier methods or a barrier method plus a hormonal method) or abstinence prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
* Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder; patients with prior malignancies must be disease-free for \>= five years
* Patients must be maintained on a stable corticosteroid regimen (no increase for 5 days) prior to the start of treatment
* Patients must be able to swallow whole capsules
* PHASE I PATIENTS:
* Must have histologically proven glioblastoma
* Must have recovered from the immediate post-operative period
* Patients going on Arm 1 or combination dose cohort must not have received prior radiation therapy, chemotherapy, immunotherapy or therapy with biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, tumor infiltrating lymphocytes \[TIL\], lymphokine-activated killer \[LAK\] or gene therapy), or hormonal therapy for their brain tumor; glucocorticoid therapy is allowed
* Patients going on Arm 2 must have received planned treatment with radiation therapy and concomitant temozolomide at least 28 days but no more than 49 days prior to starting treatment on this study; patients must have received at least 80% of planned temozolomide and radiation therapy with no grade 3 or grade 4 toxicity (except lymphopenia) attributed to the temozolomide; Arm 2 patients may not have received any other prior chemotherapy, immunotherapy or therapy with biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, TIL, LAK or gene therapy), or hormonal therapy for their brain tumor; prior Gliadel wafers are allowed; glucocorticoid therapy is allowed
* INTRATUMORAL DRUG DISTRIBUTION STUDY PATIENTS:
* Patients must have prior histologically proven glioblastoma that is progressive or recurrent following radiation therapy +/- chemotherapy
* Patients must be undergoing repeat surgery that is clinically indicated as determined by their care providers
* Patients must have measurable contrast-enhancing progressive or recurrent glioblastoma by MRI within 21 days of starting treatment; patient must be able to tolerate MRIs
* Patients may have an unlimited number of prior therapy regimens
* Patients must have recovered from severe toxicity of prior therapy; the following intervals from previous treatments are required to be eligible:

  * 12 weeks from the completion of radiation
  * 6 weeks from a nitrosourea chemotherapy
  * 3 weeks from a non-nitrosourea chemotherapy
  * 4 weeks from any investigational (not Food and Drug Administration \[FDA\]-approved) agents
  * 2 weeks from administration of a non-cytotoxic, FDA-approved agent (e.g., Tarceva, hydroxychloroquine, bevacizumab, etc.)

Exclusion Criteria:

* Patients receiving any other investigational agents are ineligible
* Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or AZD1775 (adavosertib) are ineligible; the AZD1775 (adavosertib) investigator brochure and the temozolomide package insert can be referenced for more information
* Patients on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for treatment on this protocol; patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs; patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of AZD1775 (adavosertib)
* Patients may not be on drugs known to be moderate or potent inhibitors/inducers of CYP3A4, sensitive substrates of CYP3A4, or substrates of CYP3A4 with narrow therapeutic windows
* Patients may not be on anti-coagulants (warfarin, etc.) other than low-molecular weight heparin (LMWH)
* Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible
* Pregnant women are excluded from this study because AZD1775 (adavosertib) has potential for teratogenic or abortifacients effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AZD1775 (adavosertib), breastfeeding should be discontinued if the mother is treated with AZD1775 (adavosertib)
* Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD1775 (adavosertib); in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy