FPS-ZM1 With or Without Dexamethasone for Controlling Post Operative Cerebral Edema in Patients With Glioblastoma

PRIMARY OBJECTIVE: I. Determine the maximum feasible dose (MFD) of RAGE antagonist FPS-ZM1 (FPS-ZM1) administered peri-operatively to participants with newly diagnosed or recurrent glioblastoma. SECONDARY OBJECTIVES: I. Assess the ability of FPS-ZM1 to control participants' symptoms of post-operative cerebral edema when administered as monotherapy. II. Describe the systemic pharmacokinetics and central nervous system (CNS) penetration of FPS-ZM1 based on concentrations of FPS-ZM1 in peripheral blood, cerebrospinal fluid (CSF), brain tumor tissue and resection cavity fluid (when obtainable). III. Characterize cytokine concentrations over time in brain interstitial fluid, peripheral blood and resection cavity fluid (when obtainable) by dose level. IV. Assess for evidence of RAGE inhibition in tumor tissue, CSF, brain interstitial fluid, resection cavity fluid (when obtainable) and peripheral blood by dose level. V. Qualitatively and quantitatively assess changes in volume of cerebral edema on pre-operative brain magnetic resonance imaging (MRIs) and brain MRIs performed on post-operative Days 2 and 14 across dose levels. OUTLINE: This is a dose-escalation study of FPS-ZM1 in combination with fixed-dose dexamethasone. Patients are assigned to 1 of 2 arms. ARM I (DOSE LEVELS 1-3): Starting 2 days prior to surgery, patients receive FPS-ZM1 orally (PO) daily (QD) until post operative day 11, and dexamethasone intravenously (IV) or PO QD taper until post operative day 14, in the absence of disease progression or unacceptable toxicity. On day of surgery patients undergo standard of care resection and, if possible, undergo placement of a temporary peritumoral microdialysis catheter and intracavity drain for collection of dialysate and intracavity fluid. Patients undergo urine sample collection during screening, lumbar puncture with CSF collection and computed tomography (CT) scan on study and brain MRI, and blood sample collection throughout the study. ARM II (DOSE LEVEL 4): Starting 2 days prior to surgery, patients receive FPS-ZM1 PO QD and, if needed for physiologic replacement, a smaller dose of dexamethasone IV or PO QD until post operative day 11, in the absence of disease progression or unacceptable toxicity. On day of surgery patients undergo standard of care resection and, if possible, undergo placement of a temporary peritumoral microdialysis catheter and intracavity drain for collection of dialysate and intracavity fluid. Patients undergo urine sample collection during screening, lumbar puncture with CSF collection and CT scan on study and brain MRI, and blood sample collection throughout the study. After completion of study treatment, patients are followed up at day 30.