NU-0129 in Treating Patients With Recurrent Glioblastoma or Gliosarcoma Undergoing Surgery

Inclusion Criteria: * Patients must have histologically proven glioblastoma multiforme (GBM) or gliosarcoma (GS) * Patients must have measurable disease by Response Assessment in Neuro-Oncology (RANO) 2010 criteria at the time of registration (pre-operative) * Patients must have failed at least one regimen of chemo or radiation therapy; NOTE: There is no limit to the number or types of prior therapy * The patient must be a candidate for surgical debulking (either subtotal or gross total resection); biopsy-only candidates will not be eligible * All patients must be capable to voluntarily sign an informed consent indicating that they are aware of the investigational nature of this study prior to registration * Patients must have a Karnofsky performance status of \>= 70 * Patients must have adequate bone marrow, liver, coagulation and renal function within 7days prior to study registration, as defined below: * White blood cell count (WBC) \>= 3,000/uL * Absolute neutrophil count (ANC) \>= 1,500/mm\^3 * Platelet count of \>= 100,000/mm\^3 (Note: Transfusion or growth factor may be used for eligibility outside of 7 days) * Hemoglobin \>= 8 mg/dL (Note: Transfusion may be used for eligibility outside of 7 days) * Bilirubin =\< 2 x upper limit of normal (ULN) * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2 x ULN * Creatinine =\< 1.5 x ULN * Urine protein =\< 3 x ULN * Cholesterol =\< 300 mg/dL * International normalized ration (INR) =\< 1.5 x ULN * Prothrombin time (PT)/partial thromboplastin time (PTT) =\< 1.5 x ULN * Any patient who has had a recent surgery should have recovered from all effects of the surgery and be cleared by their surgeon * Patients must have confirmed availability of archival or freshly biopsied tumor tissue meeting protocol-defined specifications (10 unstained slides) prior to study enrollment * Females of child-bearing potential (FOCBP) and males must agree to use adequate contraception (e.g. hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 28 days following completion of therapy; should a female patient, or a male patient's partner, become pregnant or suspect she is pregnant while participating in this study, the patient should inform her or his treating physician immediately * NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy * Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \> 12 months) * FOCBP must have a negative pregnancy test (either urine or serum) within 14 days prior to registration Exclusion Criteria: * Patients must not have any significant infections or medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate NU-0129 * Patients must not have a history of any other cancer unless they are in complete remission and off of all therapy for that disease for a minimum of 3 years * Note: Non-melanoma skin cancer or carcinoma in-situ of the cervix are exceptions and may be permitted after discussion with study quality assurance manager (QAM) * Patients must not have had radiation therapy within 12 weeks prior to registration * Patients must not have had prior cancer therapy (including biologic, cytotoxic, and experimental therapies, nitrosoureas, and Gliadel wafers or other surgically implantable antitumor treatment) within 21 days of registration; if questions arise, please ask the principal investigator (PI) * NOTE: Patients must not have Novocure within 24 hours * Hormonal tumor therapies should not be administered within 14 days of registration; exceptions may be discussed with the PI * Patients must not have symptomatic hypertension * Patients with known human immunodeficiency virus (HIV) infection or chronic or acute hepatitis B or C are not eligible; Note: Patients do not need to have HIV, hepatitis B, or hepatitis C testing at screening * Female patients who are pregnant or breast feeding are not eligible * Patients are not eligible if they are unwilling or unable to comply with the protocol