Azeliragon in MGMT Unmethylated Glioblastoma

NCT05986851 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CAN-401
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 8

Brief Summary

This is a phase 2 study to evaluate the safety and preliminary evidence of effectiveness of azeliragon, in combination with radiation therapy, as an initial treatment of a form of glioblastoma. Glioblastoma is a type of brain cancer that grows quickly and can invade and destroy healthy tissue. There's no cure for glioblastoma, which is also known as glioblastoma multiforme. Treatments, including surgery, radiation, and chemotherapy might slow cancer growth and reduce symptoms. New treatments of glioblastoma are needed.

Conditions

Glioblastoma

Keywords

Unmethylated

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Progression-free survival (PFS) of newly diagnosed unmethylated GBM treated with the combination of RT and azeliragon.

  Up to 2 years

Secondary Outcomes (3)

• Overall survival

  Up to 2 years

• Response rate

  Up to 2 years

• Steroid requirement

  Up to 2 years

Study Arms (1)

Daily oral azeliragon

EXPERIMENTAL

Azeliragon to be administered once daily for several days before, during, and after radiation therapy.

Drug: Azeliragon

Interventions

Azeliragon DRUG

Oral capsule

Daily oral azeliragon

Eligibility Criteria

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

You may qualify if:

• \. Histopathologically proven diagnosis of IDH-wildtype glioblastoma (GBM, WHO grade 4) according to the 2021 WHO classification (including subtypes such as gliosarcoma).
• \. Diagnosis must be established by open biopsy or tumor resection. Patients who have only had a stereotactic biopsy are not eligible.
• \. Supratentorial location. 4. MGMT promoter methylation is negative based on local CLIA-certified commercial laboratory tests.
• \. Must have recovered from the effects of surgery, postoperative infection, and other complications at the time the patient signs the informed consent and is determined to be eligible to participate in the study, as deemed eligible to participate per PI and sub-investigator.
• \. ≥ 18 years old. 7. Karnofsky performance status ≥ 60. 8. A diagnostic contrast-enhanced MRI or CT scan (if MRI is not available) of the brain must be performed preoperatively and postoperatively. The postoperative scan must be done within 21 days of the signing of informed consent prior to the initiation of radiotherapy. Preoperative and postoperative scans must be the same type. If CT scans were performed perioperatively, a CT should be performed before the signing of the informed consent.
• \. Study therapy must begin ≤ 7 weeks after the most recent brain tumor surgery.
• \. Adequate organ and bone marrow function as defined below:
• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3;
• Untransfused platelet count ≥ 75,000 cells/mm3;
• Hemoglobin \> 9.0 g/dL (Note: the use of transfusion or other intervention to achieve Hgb \>9.0 g/dL is acceptable);
• Total bilirubin ≤ 1.5 ULN
• AST (SGOT) and ALT (SGPT) ≤ 3x ULN 11. • Creatinine ≤ 1.5 ULN or creatinine clearance ≥ 60 mL/min using the CKD- EPI Creatinine Equation
• If there is history of human immunodeficiency virus (HIV) infection, patients must be on effective antiretroviral therapy, and HIV viral load must be undetectable within 6 months of study enrollment.
• If there is history of chronic hepatitis B virus (HBV) infection, patients must have either been treated or are on suppressive therapy (as indicated), and HBV viral load must be undetectable.
• If there is history of hepatitis C virus (HCV) infection, patients must have been treated, and HCV viral load must be undetectable.

You may not qualify if:

• Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free or not requiring active therapy for ≥ 3 years. (For example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible).
• Prior cranial RT or RT to the head and neck where potential field overlap may exist.
• Prior use of carmustine (Gliadel) wafers or any other intratumoral or intracavitary treatment.
• Recurrent or multicentric disease. Multicentric disease is defined as multiple discrete areas of tumor without connecting T2 signal abnormality.
• Infratentorial disease or metastatic disease beyond the brain.
• Known IDH mutation. IDH status could be determined by either immunohistochemistry or sequencing as evaluated per routine clinical care.
• Patients with a serious active infection (such as a wound infection requiring parenteral antibiotics) at the time of study entry or other serious underlying medical conditions that would impair the ability of the patient to receive protocol treatment
• Patients with any condition (e.g., psychological, geographical, etc.) that does not permit compliance with the protocol.
• Patients receiving CYP 2C8 inhibitors noted in Section 6.3
• 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
• Pregnant or breast feeding. Women of childbearing potential must a negative pregnancy test within 14 days of study entry. 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 30 days prior to study entry. 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
• Medpace, Inc.: collaborator

Study Sites (8)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Miami Cancer Institute - Baptist Health

Miami, Florida, 33176, United States

Location

Corewell Health

Royal Oak, Michigan, 48073, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Lenox Hill Hospital

New York, New York, 10021, United States

Location

The University of Oklahoma Health Science Center

Oklahoma City, Oklahoma, 73104, United States

Location

University of Utah Health Huntsman Cancer Center

Salt Lake City, Utah, 84112, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

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

• Stephen G Marcus, MD

  Cantex Pharmaceuticals

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2023
• First Posted: August 14, 2023
• Study Start: September 12, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)