• Age \>= 18 years

• Disease characteristics:

‣ Tissue-confirmed progressive or recurrent World Health Organization (WHO) Grade IV IDH wildtype glioblastoma (including molecular glioblastoma and gliosarcoma)

⁃ Previously treated with maximum feasible resection or biopsy, radiation, and temozolomide

• Have an enhancing mass on magnetic resonance imaging (MRI) amenable to resection or biopsy of the tumor (as determined by the neurosurgeon pre-operatively) and histological diagnosis of glioblastoma from a prior biopsy or surgery

• Willing to undergo clinically indicated biopsy and/or resection of their glioblastoma at Mayo Clinic in Rochester, Minnesota (MN).

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 and Karnofsky Performance Scale (KPS) \>= 70 NOTE: PS must be assessed (again) within 7 days prior to first dose of study drug

• Hemoglobin \>= 9.0 g/dL (obtained =\< 15 days prior to registration) (without transfusion or erythropoietin \[EPO\] dependency =\< 7 days prior to assessment)

• Absolute neutrophil count (ANC) \>= 1500/mm\^3 (obtained =\< 15 days prior to registration)

• Platelet count \>= 100,000/mm\^3 (obtained =\< 15 days prior to registration)

• Creatinine =\< 1.5 x upper limits of normal (ULN) OR measured or calculated creatinine clearance (per institutional standard) must be \>= 45 ml/min (obtained =\< 15 days prior to registration)

• Total bilirubin =\<1.5 x ULN OR direct bilirubin =\< ULN for patients with total bilirubin levels \>1.5 x ULN (obtained =\< 15 days prior to registration)

• Aspartate transaminase (AST) AND alanine transaminase (ALT) =\< 2.5 x ULN (obtained =\< 15 days prior to registration)

• Prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT) =\< 1.5 x ULN OR if patient is receiving anticoagulant therapy then INR or aPTT is within target range of therapy (obtained =\< 15 days prior to registration)

• Negative pregnancy test done =\< 7 days prior to registration, for persons of childbearing potential only (POCBP) Note: If testing done for eligibility is \> 72 hours prior to first dose, then pregnancy testing must be repeated, and result must be negative for patient to receive treatment.

• POCBP or able to father a child must be willing to use adequate contraception starting with first dose through 180 days after last dose

• Provide written informed consent

• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study).

• Willing to provide tissue and blood samples for correlative research purposes