Effect of Azeliragon Combined With Stereotactic Radiation Therapy in Patients With Brain Metastases

Inclusion Criteria

• Patient must have histologically or cytologically confirmed diagnosis of cancer within the past 5 years. If original histologic proof of malignancy is > 5 years, then biological [such as presence of tumor markers, circulating tumor (ctDNA), etc.], or pathological (i.e., more recent) confirmation is required (e.g., from a systemic metastasis or brain metastasis)
• Age ≥ 18
• Karnofsky performance status ≥ 50 or Eastern Cooperative Oncology Group (ECOG) ≤ 3
• Brain metastasis with a maximum tumor diameter of the largest lesion ≤ 2 cm
• Patients must have discontinued corticosteroids at least 5 days prior to SRS. (Note: This does not apply to corticosteroids administered as part of this protocol.)
• Patients must not be pregnant (positive pregnancy test) or breast feeding. Effective contraception (men and women) must be used in patients of child-bearing potential during radiotherapy and for 6 months after.
• Patients who have received prior SRS are eligible, provided that there are new non-irradiated brain lesions and that the patient is ≥ 2 months post prior cranial radiation therapy
• Patient has adequate biological parameters as demonstrated by the following blood counts at Screening (obtained ≤ 14 days prior to enrollment):
• Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L
• Platelet count ≥ 75,000/mm^3 (75 × 10^9/L)
• Hemoglobin (Hgb) ≥ 9 g/dL without transfusion or growth factor support
• Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L; Platelet count ≥ 75,000/mm^3 (75 × 10^9/L); Hemoglobin (Hgb) ≥ 9 g/dL without transfusion or growth factor support
• Patient has the following blood chemistry levels at Screening (obtained ≤ 14 days prior to enrollment):
• Aspartate aminotransferase (AST; SGOT), alanine transaminase (ALT; SGPT) ≤ 2.5 × upper limit of normal range (ULN). Total bilirubin ≤ 1.5 × ULN.
• Estimated creatinine clearance of > 60 mL/min (per Cockcroft-Gault formula)

Exclusion Criteria

• Patients with leptomeningeal disease
• Patients unable to undergo magnetic resonance imaging (MRI)
• Patients receiving Cytochrome P450 (CYP) 2C8 inhibitors as indicated in the protocol
• 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 azeliragon.
• Patients with concurrent participation in another interventional clinical trial or use of another investigational agent within 7 days of starting azeliragon. Patients who are participating in non-interventional clinical trials (e.g., QOL, imaging, observational, follow-up studies, etc.) are eligible, regardless of the timing of participation.
• Any patient that in the opinion of the principal investigator is not an appropriate candidate for this trial