Microtubule-Targeted Agent BAL101553 and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma

The following inclusion criteria were applied: * Patients must have had histologically-proven GBM * Patients must have recovered from the immediate post-operative period * Patients must have had tumor MGMT methylation status of unmethylated as determined by local pathologist using a Clinical Laboratory Improvement Act (CLIA)-approved diagnostic test; results of routinely-used methods for MGMT methylation testing (e.g. methylation-specific \[MS\]- polymerase chain reaction \[PCR\] or quantitative PCR) were acceptable * Patients must have been be able to undergo magnetic resonance imaging (MRI) of the brain with gadolinium * Patients must not have received prior radiation therapy (RT), chemotherapy, immunotherapy or therapy with a biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, tumor-infiltrating lymphocytes, lymphokine-activated killer cells, or gene therapy), or hormonal therapy for their brain tumor; glucocorticoid therapy is allowed * Patients must have had a tumor tissue form indicating availability of archived tissue from initial resection at diagnosis of GBM, completed and signed by a pathologist * Patients must have had 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/micro liter (mcL) * Platelets \>= 100,000/mcL * Hemoglobin \>= 9 g/dL * Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN), unless the patient has known Gilbert's syndrome * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN * Creatinine =\< 1.5 x ULN * Creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels \> ULN * Activated partial thromboplastin time (APTT)/partial thromboplastin time (PTT) =\< 1.5 x ULN * Sodium \>= 130 mmol/L * Patients must have been able to provide written informed consent * Patients must have had baseline MRI performed within the 21 days prior to starting treatment * Women of childbearing potential must have had a negative serum pregnancy test within 72 hours prior to the first dose of BAL101553; women of childbearing potential must have agreed to use highly-effective contraceptive methods for the duration of study participation and for an additional 90 days after the last dose of study drug; highly-effective contraceptive methods include male or female sterilization (bilateral tubal occlusion or vasectomy); intrauterine device (IUD); combined (estrogen- and progesterone-containing) hormonal contraception (oral, vaginal ring or transdermal patch) with an ethinylestradiol dose of at least 30 ug, plus use of male condoms (preferably with spermicides), female condoms, a female diaphragm or a cervical cap; or total sexual abstinence; if a woman became pregnant or suspected she was pregnant while participating in this study, she was asked to inform her treating physician immediately; male patients must have agreed not to donate sperm from the time of the first dose of study drug until 90 days after the end of treatment; male patients, without a vasectomy and with a partner of childbearing potential, must have agreed to use condoms during the study and for at least 90 days after the end of treatment; the patient should have been instructed that their female partner should use another form of contraception for the duration of the study and continue this use for at least 90 days after the last dose of study drug * Patients must have had no concurrent malignancies 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 have been disease-free for \>= 5 years * Patients must have been maintained on a stable corticosteroid regimen (no increase for 5 days) prior to the start of treatment * Patients must have been able to swallow whole capsules The following exclusion criteria were applied: * Patients receiving any other investigational agent * Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to BAL101553 * Patients on drugs that are strong inhibitors and/or inducers of CYP2C9, CYP2C19 or CYP3A4 (including enzyme-inducing anti-epileptic drugs EIAEDs\]), were not eligible for the study; patients taking non-EIAEDs were permitted to take part in the study; patients previously treated with any of the prohibited concomitant medications listed above may have been enrolled if they had been off the medication for \>= 10 days prior to the first dose of BAL101553 * Patients may not have been on coumarin anti-coagulants (warfarin, etc.); heparin, low-molecular weight heparin (LMWH), or other antithrombotic medications were permitted * Patients with gastrointestinal disease, or those who had a procedure that was expected to interfere with the oral absorption or tolerance of BAL101553 (e.g., functionally-relevant gastrointestinal obstruction, or frequent vomiting unresolved upon anti-emetic supportive care) * Patients with peripheral neuropathy \>= Common Terminology Criteria for Adverse Events (CTCAE) grade 2 * Patients with ataxia \>= CTCAE grade 2 * Patients with known acute or chronic hepatitis B or hepatitis C infection * Patients with systolic blood pressure (SBP) \>= 140 mmHg or diastolic blood pressure (DBP) \>= 90 mmHg at the screening visit were ineligible; patients with an initial clinic blood pressure (BP) \>= 140/90 mmHg may be included if SBP \< 140 mmHg and DBP \< 90 mmHg is confirmed in two subsequent BP measurements on the same day * Patients with BP combination treatment with more than two antihypertensive medications were ineligible * Significant cardiac disease or abnormality, including any of the following: * Left ventricular ejection fraction \< 50% at screening (assessed by echocardiography, cardiac MRI or multigated acquisition \[MUGA\]) * Corrected QT Fridericia's correction formula (QTcF) \> 470 ms on screening electrocardiogram (ECG), or a clinically-relevant ECG abnormality * Congenital long QT syndrome * History of sustained ventricular tachycardia, ventricular fibrillation, or torsades de pointes * Presence of atrial fibrillation with tachyarrhythmia (ventricular response rate \> 100 beats per minute \[bpm\]) * Bradycardia (heart rate \< 50 bpm) * Complete left bundle branch block. * Bifascicular block (complete right bundle branch block and anterior or posterior left hemiblock) * Myocardial infarction, acute coronary syndrome (including unstable angina), coronary revascularization procedures, or coronary arterial bypass grafting within the 6 months prior to starting study drug * Cardiac troponin (either troponin T or troponin I) \> ULN * Congestive heart failure of New York Heart Association class III or IV * Unstable angina pectoris * Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements, were ineligible * Pregnant women were excluded from this study; breastfeeding should have been discontinued if the mother was treated with BAL101553 * Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy were ineligible