Concurrent Azeliragon With Craniospinal Irradiation

NCT ID: NCT06724926

Last Updated: 2026-01-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-18
• Study Completion Date: 2031-01-31

Brief Summary

Single institution study to assess the safety of concurrent Azeliragon with craniospinal irradiation (CSI) in patients with leptomeningeal metastasis from solid tumor malignancies and high-grade gliomas.

Conditions

Solid Tumor; High-grade Glioma; Leptomeningeal Metastasis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Determination followed by Dose Expansion

Patients with leptomeningeal metastasis from a solid tumor or primary CNS high-grade glioma will be enrolled and start Azeliragon 7 days prior to CSI, during CSI, and for 7 days days after completion of CSI (Dose Determination). Patients will be monitored for dose limiting toxicities during protocol therapy.

Once the recommended dose is identified, additional patients will be treated with Azeliragon at recommended dose in combination with craniospinal irradiation (Dose Expansion).

Group Type: EXPERIMENTAL

Azeliragon

Intervention Type: DRUG

Azeliragon is orally administered. Patients start Azeliragon 7 days before CSI and take their last dose 7 days post-CSI.

The first 6 patients will start at Dose Level 1 [DL1] (Loading dose for 7 days: 30 mg twice daily; Concurrent/adjuvant dose: 20 mg once daily).

If 1 or fewer of 6 patients develop dose-limiting toxicity (DLT) then the recommended dose will be DL1. If at least 2 of 6 develops a DLT, then an additional 6 patients will be enrolled at Dose Level -1 [DL-1] (Loading dose for 7 days: 15mg twice daily; Concurrent/adjuvant dose: 10mg once daily).

If 1 or fewer out of 6 patients at DL-1 develop DLT, then the recommended dose will be DL-1. If at least 2 of 6 at DL-1 develops a DLT, then an additional 6 patients will be enrolled at Dose Level -2 [DL-2] (Loading dose for 7 days: 15mg twice daily; Concurrent/adjuvant dose: 5mg once daily).

At the recommended dose, an additional 14 patients will be enrolled for the Dose Expansion portion.

CSI

Intervention Type: PROCEDURE

Patients will receive CSI.

Interventions

Azeliragon

Azeliragon is orally administered. Patients start Azeliragon 7 days before CSI and take their last dose 7 days post-CSI.

The first 6 patients will start at Dose Level 1 [DL1] (Loading dose for 7 days: 30 mg twice daily; Concurrent/adjuvant dose: 20 mg once daily).

If 1 or fewer of 6 patients develop dose-limiting toxicity (DLT) then the recommended dose will be DL1. If at least 2 of 6 develops a DLT, then an additional 6 patients will be enrolled at Dose Level -1 [DL-1] (Loading dose for 7 days: 15mg twice daily; Concurrent/adjuvant dose: 10mg once daily).

If 1 or fewer out of 6 patients at DL-1 develop DLT, then the recommended dose will be DL-1. If at least 2 of 6 at DL-1 develops a DLT, then an additional 6 patients will be enrolled at Dose Level -2 [DL-2] (Loading dose for 7 days: 15mg twice daily; Concurrent/adjuvant dose: 5mg once daily).

At the recommended dose, an additional 14 patients will be enrolled for the Dose Expansion portion.

Intervention Type: DRUG

CSI

Patients will receive CSI.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Patient with solid tumor malignancy or high grade glioma with leptomeningeal metastasis established radiographically and/or through cerebrospinal fluid (CSF) cytology
• Patients who are candidates for radiation therapy for the treatment of leptomeningeal metastasis
• Patients with Karnofsky Performance Status of 60 or greater.
• Male or non-pregnant and non-lactating female and ≥ 18 years of age.
• Patients with absolute neutrophil count (ANC) ≥ 1.0 × 109/L, platelet count ≥ 75,000/mm3 (75 × 109/L), and hemoglobin (Hgb) ≥ 8 g/dL. Transfusion or growth factor support is allowed.
• Patients with 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, and 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.
• Patients unable to complete the English quality of life questionnaires
• Patient with extensive systemic disease and who declined standard systemic treatment options
• Patient who is unable to undergo magnetic resonance imaging (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 women

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jonathan Yang, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Locations

NYU Langone Health

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jonathan Yang, MD, PhD

Role: CONTACT

Jonathan.Yang@nyulangone.org

212-731-6276

Cancer Trials Office

Role: CONTACT

cancertrials@nyulangone.org

212-263-4432

Other Identifiers

24-00982

Identifier Type: -

Identifier Source: org_study_id