Concurrent Azeliragon With Craniospinal Irradiation

A Phase IB Study to Assess Safety of Concurrent Azeliragon With Craniospinal Irradiation in Patients With Leptomeningeal Metastasis From Solid Tumor Malignancies or High-Grade Gliomas

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Solid Tumor; High-grade Glioma; Leptomeningeal Metastasis
• Intervention / Treatment: Drug: Azeliragon; Procedure: CSI

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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).

Drug: 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.; Procedure: CSI; Patients will receive CSI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients with Dose-Limiting Toxicities (DLTs) at Dose Level 1	DLTs assess using Common Terminology Criteria for Adverse Events (CTCAE) v 5.0.	Up to Week 4
Number of Patients with DLTs at Dose Level -1	DLTs assess using CTCAE v 5.0.	Up to Week 4
Number of Patients with DLTs at Dose Level -2	DLTs assess using CTCAE v 5.0.	Up to Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Central nervous system (CNS) progression-free survival (PFS)	CNS PFS is defined as time from randomization until CNS progression or death, whichever occurs first.	Up to Month 13 (12 Months Post-Protocol Therapy)
Overall Survival (OS)	OS is defined as time from randomization until death.	Up to Month 13 (12 Months Post-Protocol Therapy)

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Jonathan Yang, MD, PhD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2031

Study Registration Dates

• First Submitted: December 6, 2024
• First Submitted That Met QC Criteria: December 6, 2024
• First Posted (Actual): December 9, 2024

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Meningeal Neoplasms; Central Nervous System Neoplasms; Glioma; Meningeal Carcinomatosis; azeliragon
• Other Study ID Numbers: 24-00982

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified participant data from the final research dataset will be shared upon reasonable request beginning 9 to 36 months after publication or as required by a condition of awards or supporting agreements, provided the requesting investigator executes a data use agreement with NYU Langone Health. This instance of data sharing will also require separate IRB review as well as review from NYU Langone's Data Sharing Strategy Board (DSSB). Requests should be directed to: Jonathan.Yang@nyulangone.org. The protocol and statistical analysis plan will be posted on Clinicaltrials.gov only as required by federal regulation or supporting awards and agreements.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: The investigator who proposed to use the data upon reasonable request. Requests should be directed to Jonathan.Yang@nyulangone.org. To gain access, data requestors will need to sign a data access agreement. This instance of data sharing will also require separate IRB review as well as review from NYU Langone's DSSB.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No