Neoplasms

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Pancreatic Neoplasms

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Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

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All Drugs and Chemicals

Tin Fluorides

Azeliragon will be orally administered to 3 groups of 6 subjects, with escalation of dosing occurring with each subsequent group.

Dose Level 1 consists of a loading dose of 15mg once daily for 6 days, followed by a continuous dose of 5mg once daily for the remainder of the study.

Dose Level 2 consists of a loading dose of 15mg twice daily for 6 days, followed by a continuous dose of 10mg once daily for the remainder of the study.

Dose Level 3 consists of a loading dose of 30mg twice daily for 6 days, followed by a continuous dose of 20mg once daily for the remainder of the study.

Escalation will continue until stopping rules are met or the highest defined dose level is reached. The trial will be closed to accrual if the first dose level is deemed intolerable.

Azeliragon is an orally administered inhibitor of Receptor for Advanced Glycation Endproducts (RAGE) which is formulated as a 5mg hard gelatin capsule.

Azeliragon

Stephen Marcus, MD

Andrew Hendifar, MD

Warren Brenner, MD

Marc Uemura, MD

Nathan Bahary, MD

Ki Chung, MD

Donald Richards, MD

This is an open label study to determine the safety and preliminary evidence of a therapeutic effect of azeliragon in patients refractory to first-line or second-line treatment of metastatic pancreatic cancer.

Study of Effect of Azeliragon in Patients Refractory to First-Line Metastatic Pancreatic Cancer

A Phase I/II Open Label Study to Assess Safety and Preliminary Evidence of a Therapeutic Effect of Azeliragon in Patients Refractory to First-Line Treatment of Metastatic Pancreatic Cancer

Assessment of the recommended phase 2 dose (RP2D) of azeliragon in patients with metastatic pancreatic cancer.

The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type, severity (as defined by the NIH CTCAE, version 5.0), seriousness, duration, and relationship to study treatment.

Pain as determined by Brief Pain Assessment at 2, 4, 6 and 8 weeks after initiation of treatment.

Change in average daily total opioid consumption (in mg of morphine equivalent doses) at Weeks 2, 4, 6, and 8.

Disease control as indicated by Complete Response + Partial Response + Stable Disease at 2 months and longer as determined by RECIST criteria, provided CT or MRI scans were performed consistent with standard of care.

Measurement of time from first dose of azeliragon until death from any cause.

Measurement of change in grading of patient status based on descriptions in the ECOG performance status scale. Grading scale has a minimum value of 0 and maximum value of 5, with 0 being the best outcome and 5 being the worst.

Change from baseline in serum albumin concentration.

Cantex Pharmaceuticals

Symptoms and General Pathology

Nervous System Diseases

Neoplasm Metastasis

Neoplasms, Second Primary

Brain Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

Neuroprotective Agents

Dexamethasone

Prednisolone

Dexamethasone acetate

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Histamine H2 Antagonists

Proton Pump Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Protective Agents

In the Phase 1 portion of the study, three treatment regimens will be systematically evaluated:

1. Azeliragon + SRS + loading corticosteroid dose (LD) + corticosteroid taper (CT)
2. Azeliragon + SRS + loading corticosteroid dose (LD)
3. Azeliragon + SRS

The starting cohort will receive Regimen #2, and depending on the tolerability, participants will be allocated to subsequent cohorts as follows: if Regimen #2 is not well tolerated, participants will be allocated to Regimen #1; if #2 is well tolerated, participants will be allocated to Regimen #3.

Once a Regimen has been identified as safe and tolerable, it will be used for the Phase 2 portion of the study.

Dosing will begin on Day 0 with the loading dose and continue daily through Day 7. Starting on Day 8, dosing will resume with the continuous dose until disease progression or 8 weeks. If there is evidence of antitumor effect at 8 weeks, dosing may continue for up 2 two years.

All doses are taken orally. There are three levels of dosing, including a starting dose and two lower levels of dosing. Participants will start with the starting dose, and in the event of the dose limiting toxicities, the dose will be reduced as described below.

Starting Dose Level: 30 mg twice daily (Loading Dose) or 20 mg once daily (Continuous Dose) Dose Level -1: 15 mg twice daily (Loading Dose) or 10 mg once daily (Continuous Dose) Dose Level -2: 15 mg once daily (Loading Dose) or 5 mg once daily (Continuous Dose)

Patients will undergo standard of care SRS as per the treating facility's policies.

Stereotactic radiosurgery

Two corticosteroid regimens are used depending on the study cohort. Cohorts 1 and 2 will receive the loading dose (LD). Only Cohort 1 will receive the corticosteroid taper (CT).

LD: Oral (8 mg) or IV bolus dose (10 mg) of dexamethasone or 40 to 80 mg of methylprednisolone on the day of SRS CT: Oral 2-4 mg of dexamethasone twice daily for 5 days and then 2-4 mg daily for 5 days at the discretion of the treating physician (concurrent use of a proton pump inhibitor or H2 receptor antagonists are encouraged during the CT).

Corticosteroid

Minesh Mehta, M.D.

Miguel A Ramirez Menendez

Yazmin Odia, M.D.

To determine the safety and efficacy of using the drug azeliragon combined with stereotactic radiosurgery. Specifically, to determine if this combination will lead to improved response in the brain (tumor shrinking in size) and overall tumor control (how long tumor remains controlled).

Effect of Azeliragon Combined With Stereotactic Radiation Therapy in Patients With Brain Metastases

A Phase I/II Study to Assess Safety and Preliminary Evidence of a Therapeutic Effect of Azeliragon Combined With Stereotactic Radiation Therapy in Patients With Brain Metastases

A DLT of the azeliragon and corticosteroid regimen is defined as any central nervous system (CNS)-specific Grade ≥ 2 toxicity requiring corticosteroid treatment or any Grade ≥ 3 events that are not clearly due to the underlying disease or extraneous causes. DLTs will be considered up to four weeks after SRS.

Participants are evaluated for treatment-related adverse events (AEs). The total count of treatment-related AEs for all participants and those specifically in the central nervous system will be calculated. CNS treatment-related adverse events will be reported as percent of total treatment-related AEs.

Response and progression will be evaluated using the Response Assessment in Neuro-Oncology (RANO) criteria for brain metastasis (RANO-BM). The percent of patients with a complete response (CR) or partial response (PR) will be categorized individually and then together will be used to compare to the historical comparator of 24% with SRS alone.

Response and progression will be evaluated using RANO-BM. The percent of patients with CR, PR, or stable disease (SD) will be calculated.

Response and progression will be evaluated using RANO-BM. The percent of patients with CR, PR, or SD will be calculated.

Local failure will be defined using the following criteria: For lesions measuring more than 5 mm in the baseline (volumetric) scan: At least 50% increase in the product of the two largest perpendicular diameters (compared to the smallest product measured for the same lesion). For lesions measuring 5 mm or less in the baseline (volumetric) scan: At least 100% increase in the product of the two largest perpendicular diameters (compared to the smallest product measured for the same lesion). Radiation necrosis will not be considered tumor progression.

Lesion-specific tumor control rate is defined as the percent of lesions that do not meet criteria for local failure as defined above.

The following tests are included:

* Hopkins Verbal Learning Test (HVLT)
* Controlled Oral Word Association Test (COWAT)
* Trail Making Test Part A
* Trail Making Test Part B
* Grooved Pegboard

HVLT raw scores are derived for Total Recall, Delayed Recall, and Retention (% retained). COWAT is measured by summing the number of acceptable words produced for three separate letters during one minute each. The trail making tests are measured by the time they take to complete. The grooved pegboard is scored by the amount of time it takes to place the pegs correctly in the pegboard. Higher scores on HVLT and COWAT and faster times on the trail making and pegboard indicate better neurocognitive function. All tests are then standardized based on published norms and transformed so that higher values represent improved cognition.

The endpoint is defined as a decline of greater than 1 standard deviation from baseline on at least 1 of the 5 neurocognitive tests.

PROs will be assessed using the MD Anderson Symptom Inventory for brain tumors (MDASI-BT), a validated assessment in people with brain metastases. It is a 28-item questionnaire that includes 13 symptom severity items, 6 symptom interference items, and 9 brain-tumor specific symptom items. Experience of each item "in the last 24 hours" is rated on a 10-point Likert scale where a higher score indicates worse outcomes.

Ratings are averaged into several subscale scores: mean core symptom severity, mean brain tumor symptom severity, and mean interference. The change score from baseline to 24 months will be calculated by subtracting the 12-month overall score from the baseline overall score. Positive values indicate improved outcomes and negative values indicate worse outcomes.

European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 consists of 30 items and measures an individual's functioning and symptoms for all cancer types. Questions are grouped into 5 multi-item functional scales; 3 multi-item symptom scales; a 2-item global health status scale; 5 single items assessing additional symptoms commonly reported by cancer patients, and 1 item on the financial impact of the disease.

Raw QLQ-C30 scores are transformed to standardized scores (0 to 100); a higher score represents a better level of functioning or a worse level of symptoms. A Summary Score is calculated from the mean of 13 of the 15 scales (excluding Global Quality of Life and Financial Impact scales). The symptom scales are reversed to obtain uniform direction of all scales.

The change score from baseline to 24 months will be calculated by subtracting the 24-month score from the baseline score. Negative values indicate improved QOL.

EORTC QLQ-BN 20 consists of 20 items and measures the functioning and symptoms of patients with intracranial malignant disease. Questions can be grouped into 3 multi-item functional scales (visual disorder, motor dysfunction, communication deficit), 7 single items (headaches, seizures, drowsiness, itchy skin, hair loss, weakness of legs and bladder control) and 1 multi-item scale on future uncertainty.

Scoring is on a scale of 0 to 80, with higher scores indicating worse symptoms. The change score from baseline to 24 months will be calculated by subtracting the 24-month score from the baseline score. Positive values indicate improved symptoms.

Miami Cancer Institute

Cantex Pharmaceuticals Inc.

Baptist Health South Florida

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

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

Stephen G Marcus, MD

Jenna Bourdeau

Paul Ferguson

Anais Vega

Mary Martin, RN

Prakash Chinnaiyan, MD

Jiayi Huang, M.D.

Tamika Wong

John Boockvar, MD

Oleta Korah, RN

Neurooncology CoordinationStaff

Jonathan Yang, MD

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.

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.

Azeliragon in MGMT Unmethylated Glioblastoma

A Phase II Study to Assess Safety and Preliminary Evidence of a Therapeutic Effect of Azeliragon in Patients With MGMT Unmethylated Glioblastoma

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

Overall survival (OS) of newly diagnosed unmethylated GBM after RT and azeliragon

To evaluate overall response rate and duration of response as per RANO criteria

Change in requirement of dexamethasone after RT

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Effect of Azeliragon in Patients Refractory to First-Line Metastatic Pancreatic Cancer	NCT05766748	Metastatic Panc...	Azeliragon	18 Years - 80 Years	Cantex Pharmaceuticals
Study of Effect of Azeliragon in Patients Refractory to First-Line Metastatic Pancreatic Cancer	NCT05766748	Metastatic Panc...	Azeliragon	18 Years - 80 Years	Cantex Pharmaceuticals
Effect of Azeliragon Combined With Stereotactic Radiation Therapy in Patients With Brain Metastases	NCT05789589	Cancer Metastasis Metastatic Canc... Brain Metastase... Brain Metastase...	Azeliragon Stereotactic ra... Corticosteroid	18 Years -	Baptist Health South Florida
Azeliragon in MGMT Unmethylated Glioblastoma	NCT05986851	Glioblastoma	Azeliragon	18 Years -	Cantex Pharmaceuticals
Effect of Azeliragon Combined With Stereotactic Radiation Therapy in Patients With Brain Metastases	NCT05789589	Cancer Metastasis Metastatic Canc... Brain Metastase... Brain Metastase...	Azeliragon Stereotactic ra... Corticosteroid	18 Years -	Baptist Health South Florida

Spots Global Cancer Trial Database for azeliragon

Every month we try and update this database with for azeliragon cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for azeliragon

Every month we try and update this database with for azeliragon cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for azeliragon cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.