Azeliragon and Chemoradiotherapy in Newly Diagnosed Glioblastoma

NCT05635734 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: CAN 2012022-002801-36
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

Brief Summary

This is an open label study to determine the safety and preliminary evidence of a therapeutic effect of azeliragon in patients with newly diagnosed glioblastoma receiving concurrent radiation and temozolomide.

Conditions

Glioblastoma

Keywords

Azeliragon; Newly diagnosed glioblastoma; Dose finding; Temozolomide; Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Recommended phase 2/3 dose

  To assess the recommended phase 2/3 dose (RP2/3D) in mg/day of azeliragon in patients with newly diagnosed glioblastoma receiving concurrent radiation and temozolomide. Dose limiting toxicities were defined as listed AEs, dose-reductions, treatment interruptions, or discontinuation occurring during the DLT period (28 days), which are attributable (definite, probable, possible) to azeliragon will be classified as a DLT. 6 patients must be treated at that dose level with ≤ 1 DLT observed

  Throughout the DLT observation period, approximately 28 days per patient

Secondary Outcomes (7)

• Incidence of adverse events (AEs)

  Throughout the study period, approximately 2 years per patient

• Incidence of serious adverse events (SAEs)

  Throughout the study period, approximately 2 years per patient

• Disease control rate (DCR)

  Throughout the study period, approximately 2 years per patient

• Progression-free survival (PFS)

  Throughout the study period, approximately 2 years per patient

• Overall survival (OS)

  Throughout the study period, approximately 2 years per patient

Study Arms (1)

Experimental arm

EXPERIMENTAL

Patients will receive azeliragon for up to 2 years or as long as the patient and study investigator feel that a therapeutic benefit is possible. Patients will receive involved field radiation therapy and temozolomide consisting of fractionated focal irradiation in daily fractions of 2 Gy given 5 days/week for 6 weeks, for a total of 60 Gy, plus concomitant daily temozolomide (TMZ; 75 mg/m2/day, 7 days/week from the first to the last day of radiotherapy), followed by six cycles of adjuvant TMZ (150-200 mg/m2/day for 5 days during each of six 28-day cycles.

Drug: Azeliragon 5 mg; Drug: Azeliragon 10 mg; Drug: Azeliragon 20 mg

Interventions

Azeliragon 5 mg DRUG

Azeliragon 5 mg once a day (loading initial dose for 6 days of 10 mg daily). Patients will receive azeliragon for up to 2 years or as long as the patient and study investigator feel that a therapeutic benefit is possible. Patients will receive involved field radiation therapy and temozolomide consisting of fractionated focal irradiation in daily fractions of 2 Gy given 5 days/week for 6 weeks, for a total of 60 Gy, plus concomitant daily temozolomide (TMZ; 75 mg/m2/day, 7 days/week from the first to the last day of radiotherapy), followed by six cycles of adjuvant TMZ (150-200 mg/m2/day for 5 days during each of six 28-day cycles.

Experimental arm

Azeliragon 10 mg DRUG

Azeliragon 10 mg once a day (loading initial dose for 6 days of 15 mg twice a day). Patients will receive azeliragon for up to 2 years or as long as the patient and study investigator feel that a therapeutic benefit is possible. Patients will receive involved field radiation therapy and temozolomide consisting of fractionated focal irradiation in daily fractions of 2 Gy given 5 days/week for 6 weeks, for a total of 60 Gy, plus concomitant daily temozolomide (TMZ; 75 mg/m2/day, 7 days/week from the first to the last day of radiotherapy), followed by six cycles of adjuvant TMZ (150-200 mg/m2/day for 5 days during each of six 28-day cycles.

Experimental arm

Azeliragon 20 mg DRUG

Azeliragon 20 mg once a day (loading initial dose for 6 days of 30 mg twice a day). Patients will receive azeliragon for up to 2 years or as long as the patient and study investigator feel that a therapeutic benefit is possible. Patients will receive involved field radiation therapy and temozolomide consisting of fractionated focal irradiation in daily fractions of 2 Gy given 5 days/week for 6 weeks, for a total of 60 Gy, plus concomitant daily temozolomide (TMZ; 75 mg/m2/day, 7 days/week from the first to the last day of radiotherapy), followed by six cycles of adjuvant TMZ (150-200 mg/m2/day for 5 days during each of six 28-day cycles.

Experimental arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have histologically confirmed newly diagnosed glioblastoma (GBM, world health organization (WHO) grade IV). The histological diagnosis must have been made after biopsy or neurosurgical tumor resection.
• Note: Patients should be isocitrate dehydrogenase (IDH) wild type diagnosed locally
• The local O-6-Methylguanine-DNA Methyltransferase (MGMT) report determination should be available and should be uploaded to the electronic case report form (eCRF).
• Patient should have had a gross total or subtotal resection performed \< 7 weeks prior to enrollment, documented at postoperative MRI. Patients who have had a biopsy only without resection are not eligible.
• Patient deemed suitable by the treating physician to receive the standard radiotherapy regimen in combination with temozolomide.
• Male or non-pregnant and non-lactating female and ≥ 18 to ≤ 70 years of age.
• Patient may have received and continue to receive corticosteroids, but must be on a stable or decreasing dose for at least 14 days prior to first dose of study treatment.
• Patient has not received prior chemotherapy or radiotherapy.
• Patient has adequate biological parameters as demonstrated by the following blood counts at Screening (obtained ≤ 14 days prior to enrollment) and at Baseline-Day 0: Absolute neutrophil count (ANC) ≥ 1.0 × 109/L; Platelet count ≥ 75,000/mm3 (75 × 109/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) and at Baseline-Day 0:
• aspartate amino-transferase (AST)(SGOT), alanine transferase (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)
• Patients with a QTC of ≤ 480 msec
• Patient has ECOG performance status of ≤ 2
• 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.

You may not qualify if:

• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for \> 5 years
• Patients with any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.
• Patients who have had treatment with any investigational cancer drug prior to the first dose of study treatment.
• Patient has experienced an increase of ECOG to \> 2 between Screening and the time of first dose with azeliragon.
• Patients receiving CYP2C8 inhibitors
• 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 azeliragon.
• Patients with concurrent participation in another interventional clinical trial or use of another investigational agent within 14 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.

Sponsors & Collaborators

• Cantex Pharmaceuticals: lead

Study Sites (4)

Hospital del Mar

Barcelona, Barcelona, 08003, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Barcelona, 08036, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Madrid, 28041, Spain

Location

Related Publications (1)

• Comitre-Mariano B, Segura-Collar B, Vellila-Alonso G, Contreras R, Hernandez-Lain A, Valiente M, Sepulveda JM, Marcus SG, Garcia-Posadas G, Jimenez-Roldan L, Perez-Nunez A, Gargini R. S100A proteins show a spatial distribution of inflammation associated with the glioblastoma microenvironment architecture. Theranostics. 2025 Jan 1;15(2):726-744. doi: 10.7150/thno.100638. eCollection 2025.

  PMID: 39744679 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

azeliragon

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Juan Sepúlveda

  Hospital Universitario 12 de Octubre

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2022
• First Posted: December 2, 2022
• Study Start: September 5, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4)