Phase I Study to Determine the Safety and Tolerability of the Oral Microtubule Destabilizer BAL101553 in Combination With Standard Radiation in Patients With MGMT Promoter Unmethylated Newly Diagnosed Glioblastoma
This Phase I study investigated the side-effects and best dose of microtubule-targeted agent BAL101553 when given together with radiation therapy in treating patients with newly-diagnosed O6-methylguanine-DNA methyltransferase (MGMT) promoter unmethylated glioblastoma (GBM). Drugs used in chemotherapy, such as microtubule-targeted agent BAL101553, work in different ways to stop the growth of tumor cells, either by killing the cells, stopping them from dividing, or stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving microtubule-targeted agent BAL101553 and radiation therapy may work better in treating patients with GBM.
• 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