Trial Title:
Azeliragon in MGMT Unmethylated Glioblastoma
NCT ID:
NCT05986851
Condition:
Glioblastoma
Conditions: Official terms:
Glioblastoma
Conditions: Keywords:
Unmethylated
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Azeliragon
Description:
Oral capsule
Arm group label:
Daily oral azeliragon
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.
Detailed description:
The study to be conducted is a phase 2 study in newly diagnosed "unmethylated"
glioblastoma.
As compared to "methylated" glioblastoma "unmethylated" glioblastoma carries a worse
prognosis, as it is resistant to temozolomide, the most commonly prescribed
chemotherapeutic treatment. Based upon pre-clinical evidence suggesting that azeliragon
may enhance the effectiveness of radiation, as well as have a delaying effect on disease
progression, this study will combine daily oral azeliragon with radiation treatment,
followed by continued administration of azeliragon after completion of radiation therapy.
Azeliragon is administered once daily as an oral capsule. In previous studies in patients
with Alzheimer's disease and in normal volunteers, azeliragon was well tolerated for up
to 18 months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
1. Histopathologically proven diagnosis of IDH-wildtype glioblastoma (GBM, WHO
grade 4) according to the 2021 WHO classification (including subtypes such as
gliosarcoma).
2. Diagnosis must be established by open biopsy or tumor resection. Patients who
have only had a stereotactic biopsy are not eligible.
3. Supratentorial location. 4. MGMT promoter methylation is negative based on
local CLIA-certified commercial laboratory tests.
5. 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.
6. ≥ 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.
9. Study therapy must begin ≤ 7 weeks after the most recent brain tumor surgery.
10. 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.
12. Females of childbearing potential (defined as a female who is
non-menopausal or surgically sterilized) must be willing to use an
acceptable method of birth control (i.e., hormonal contraceptive,
intra-uterine device, diaphragm with spermicide, condom with spermicide,
or abstinence) for the duration of the study. Should a woman become
pregnant or suspect she is pregnant while participating in this study, she
must inform her treating physician immediately 13. 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 (legally authorized
representative permitted).
Exclusion Criteria:
1. 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).
2. Prior cranial RT or RT to the head and neck where potential field overlap may exist.
3. Prior use of carmustine (Gliadel) wafers or any other intratumoral or intracavitary
treatment.
4. Recurrent or multicentric disease. Multicentric disease is defined as multiple
discrete areas of tumor without connecting T2 signal abnormality.
5. Infratentorial disease or metastatic disease beyond the brain.
6. Known IDH mutation. IDH status could be determined by either immunohistochemistry or
sequencing as evaluated per routine clinical care.
7. 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
8. Patients with any condition (e.g., psychological, geographical, etc.) that does not
permit compliance with the protocol.
9. Patients receiving CYP 2C8 inhibitors noted in Section 6.3
10. Patient is unwilling or unable to comply with study procedures, including, but not
limited to self-administration of oral medication
11. Patients with a gastrointestinal condition that could interfere with swallowing or
absorption
12. 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
13. 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
-
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Colorado Anschutz Medical Campus
Address:
City:
Aurora
Zip:
80045
Country:
United States
Facility:
Name:
Miami Cancer Institute - Baptist Health
Address:
City:
Miami
Zip:
33176
Country:
United States
Facility:
Name:
Corewell Health
Address:
City:
Royal Oak
Zip:
48073
Country:
United States
Facility:
Name:
Washington University in St. Louis
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Facility:
Name:
Lenox Hill Hospital
Address:
City:
New York
Zip:
10021
Country:
United States
Facility:
Name:
The University of Oklahoma Health Science Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Facility:
Name:
University of Utah Health Huntsman Cancer Center
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Facility:
Name:
University of Washington
Address:
City:
Seattle
Zip:
98109
Country:
United States
Start date:
September 12, 2023
Completion date:
June 30, 2025
Lead sponsor:
Agency:
Cantex Pharmaceuticals
Agency class:
Industry
Collaborator:
Agency:
Medpace, Inc.
Agency class:
Industry
Source:
Cantex Pharmaceuticals
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05986851
