Window of Opportunity Study of Lixumistat in Patients With Newly Diagnosed Glioblastoma

Prior treatment

• Patients who are receiving any other investigational agents for GBM treatment.
• Received any prior treatment for GBM.
• Patient on medications with a similar mechanism of action (i.e., oxidative phosphorylation inhibitors) to Lixumistat including the anti-diabetic medication metformin. However, use of anti-diabetic medications with alternative mechanism(s) of action are permitted. NOTE: patients receiving metformin may be eligible to participate if they are transferred to a different anti-diabetic medication and undergo a washout period of 24-hours from last dose of metformin to administration of the first dose of Lixumistat.

Other illness

• Known histological diagnosis of malignant brain tumor other than Glioblastoma (GBM).
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Lixumistat.
• Patients with uncontrolled intercurrent illness.

Lab values

• Patients who are unable to undergo contrast-enhanced MRI for any reason (for example, patients with a glomerular filtration rate \[GFR\] \< 30 mL/min, patients with a pacemaker that is incompatible with MRI, have metallic implants that are unable to undergo an MRI, etc.).

• Patient must be ≥18 years of age.
• Patients with newly-diagnosed Glioblastoma (GBM) for whom neurosurgical tumor resection is indicated and planned according to the assessment of the treating physician as per treating physician or neurosurgeon.
• Patient must have Karnofsky Performance Status (KPS) ≥ 70.
• Magnetic resonance imaging (MRI) scan performed within 21 days prior to starting protocol treatment.
• For women (any individual assigned female at birth) who are not postmenopausal (i.e., \< 2 years after last menstruation) or surgically sterile (absence of ovaries and/or uterus) and who are sexually active, agreement to use a highly effective method of contraception during the Treatment Period and for at least 6 months after the last dose of study treatment.
• Male patients (any individual assigned male at birth) of reproductive potential must avoid pregnancy in partners who are women of childbearing potential, and such partners should not consider getting pregnant during the study and for at least 6 months after treatment is discontinued or longer if requested by local authorities. Male patients must not donate semen for 6 months after the last dose of study treatment.
• Patient understands the procedures and investigational nature of the trial medication and agrees to comply with trial requirements by providing written informed consent.
• Life expectancy ≥ 3 months at the start of treatment in the opinion of the Investigator.
• Patient must have adequate bone marrow function as evidenced by:
  • Absolute neutrophil count (ANC) ≥ 1000 cells/µL
  • Hemoglobin \>8 g/dL (Patients are allowed to be transfused to this level)
  • Platelets ≥100 × 109 platelets/L.
• Patient must have adequate hepatic function as evidenced by:
  • Serum total bilirubin ≤1.5 × upper limit of normal (ULN), unless considered due to Gilbert's disease or disease involvement following approval by the Lead Principal Investigator
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT))/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase (SGPT)): ≤3 × institutional ULN
• Patient must have adequate renal function as evidenced by:
  • Creatinine clearance \>30 mL/min (patients with mild or moderate renal impairment) based on the Cockcroft-Gault glomerular filtration rate (GFR) estimation or alternative estimation of renal function, such as Modified Diet in Renal Disease (MDRD) or Chronic Kidney Disease-Epidemiology Collaborative Group (CKD-EPI) equations.