Azeliragon With Craniospinal Irradiation for the Treatment of Leptomeningeal Metastasis from Solid Tumor Cancer or High-grade Gliomas

Inclusion Criteria

• Patient with progressive solid tumor malignancy or high-grade glioma with leptomeningeal metastasis established radiographically and/or through CSF cytology after standard of care
• Patients who are candidates for radiation therapy for the treatment of leptomeningeal metastasis
• Patients with Karnofsky performance status (KPS) of 60 or greater
• Male or non-pregnant and non-lactating female and ≥ 18 years of age
• Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L. Transfusion or growth factor support is allowed
• Platelet count ≥ 75,000/mm^3 (75 × 10^9/L). Transfusion or growth factor support is allowed
• Hemoglobin (Hgb) ≥ 8 g/dL. Transfusion or growth factor support is allowed
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × upper limit of normal range (ULN), unless liver metastases are present, then ≤ 5 x ULN is acceptable
• Total bilirubin ≤ 1.5 × ULN
• Estimated creatinine clearance of > 30 mL/min (per Cockroft-Gault formula)
• Patient has been informed about the nature of the study, and has agreed to participate in the study, and signed the informed consent form (ICF) prior to participation in any study-related activities

Exclusion Criteria

• Patient has a life expectancy, per investigator assessment, of less than 2 months
• Patient with extensive systemic disease and who declined standard systemic treatment options
• Patient who is unable to undergo MRI brain and spine with gadolinium contrast * Previous radiotherapy to the intended treatment site that precludes developing a treatment plan that respects normal tissue tolerance
• Active, uncontrolled bacterial, or fungal infection(s) requiring systemic therapy
• Patient has a concomitant serious medical or psychiatric illness that, in the opinion of the investigator, could compromise the patient's safety or the study data integrity * Patient is unwilling or unable to comply with study procedures, including, but not limited to self-administration of oral medication
• Patients with a gastrointestinal condition that could interfere with swallowing or absorption
• Females of childbearing potential who are sexually active or males with female partners of childbearing potential, where either the female or the male is unwilling to use a highly effective method of contraception during the trial and for 6 months after the last administration of study drug
• Pregnant or lactating