Study of Effect of Azeliragon in Patients Refractory to Prior Treatment of 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 Prior Treatment of Metastatic Pancreatic Cancer

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

Study Overview

• Status: Recruiting
• Conditions: Metastatic Pancreatic Cancer
• Intervention / Treatment: Drug: Azeliragon

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Stephen Marcus, MD; Phone Number: 954-315-3660; Email: smarcus@cantex.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
      • Contact: Andrew Hendifar, MD; Phone Number: 310-423-2217; Email: Andrew.Hendifar@cshs.org
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Recruiting
      • Boca Raton Regional Hospital, Lynn Cancer Institute
      • Contact: Warren Brenner, MD; Phone Number: 561-955-6400; Email: wbrenner@baptisthealth.net
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Recruiting
      • Williamette Valley Cancer Institute and Research Center
      • Contact: Marc Uemura, MD; Phone Number: 541-683-5001; Email: marc.uemura@usoncology.com
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Recruiting
      • AHN Cancer Institute - Allegheny General Hospital
      • Contact: Nathan Bahary, MD; Phone Number: 412-359-6391; Email: nathan.bahary@ahn.org
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Recruiting
      • Prisma Health - Upstate
      • Contact: Ki Chung, MD; Phone Number: 864-455-3600; Email: ki.chung@prismahealth.org
  • Texas
    • Tyler, Texas, United States, 75702
      • Recruiting
      • Texas Oncology - Northeast Texas
      • Contact: Donald Richards, MD; Phone Number: 903-579-9800; Email: donald.richards@usoncology.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient must have histologically confirmed locally advanced or metastatic adenocarcinoma of the pancreas for which potential curative measures, such as resection of an isolated metastasis, are not available.
2. Patient should have previously been treated with a Gemcitabine/Abraxane or FOLFIRINOX- based regimen.
3. Toxicity from prior chemotherapy other than alopecia has recovered to Grade ≤ 1 (CTCAE 1.0) or are at baseline (such as stable G2 neuropathy).
4. Male or non-pregnant and non-lactating female and ≥ 18 to ≤ 80 years of age.
5. 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

6. Patient has the following blood chemistry levels at Screening (obtained ≤ 14 days prior to enrollment) and at Baseline-Day 0:

   • AST (SGOT), ALT (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.
   • Estimated creatinine clearance of > 60 mL/min (per Cockroft-Gault formula)
7. Patient has ECOG performance status of ≤ 2
8. Patient has been informed about the nature of the study, and has agreed to participate in the study, and signed the Informed Consent Form prior to participation in any study-related activities.

Exclusion Criteria:

1. Patient has a life expectancy, per investigator assessment, of less than 3 months.
2. Patient has experienced an increase of ECOG to > 2 between Screening and the time of first dose with study drug.
3. Patient has active, uncontrolled bacterial, or fungal infection(s) requiring systemic therapy.
4. Patients receiving CYP 2C8 inhibitors noted in Section 5.3 of the protocol.
5. 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.
6. Patient is unwilling or unable to comply with study procedures, including, but not limited to self-administration of oral medication.
7. Patients with a gastrointestinal condition that could interfere with swallowing or absorption.
8. 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.
9. Patients with concurrent participation in another interventional clinical trial or use of another investigational agent within 14 days of starting study drug. Patients who are participating in non-interventional clinical trials (e.g., quality of life, imaging, observational, follow-up studies, etc.) are eligible, regardless of the timing of participation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment Group; Azeliragon will be orally administered to 5 groups of 6 subjects, with escalation of dosing occurring with each subsequent group. Dose Level 1 is a loading dose of 15mg once daily for 6 days, followed by a dose of 5mg once daily for the rest of the study. Dose Level 2 is a loading dose of 15mg twice daily for 6 days, followed by a dose of 10mg once daily for the rest of the study. Dose Level 3 is a loading dose of 30mg twice daily for 6 days, followed by a dose of 20mg once daily for the rest of the study. Dose Level 4 is a loading dose of 30mg twice daily for 6 days, followed by a dose of 15mg twice daily for the rest of the study. Dose Level 5 is a loading dose of 30mg twice daily for 6 days, followed by a dose of 25mg twice daily for the rest 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.

Drug: Azeliragon; Azeliragon is an orally administered inhibitor of Receptor for Advanced Glycation Endproducts (RAGE) which is formulated as a 5mg hard gelatin capsule.; Other Names: TTP488

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended Phase 2 Dose	Assessment of the recommended phase 2 dose (RP2D) of azeliragon in patients with metastatic pancreatic cancer.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AE and SAE Frequency	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.	8 weeks
Pain after treatment initiation	Pain as determined by Brief Pain Assessment at 2, 4, 6 and 8 weeks after initiation of treatment.	8 weeks
Average daily opioid consumption.	Change in average daily total opioid consumption (in mg of morphine equivalent doses) at Weeks 2, 4, 6, and 8.	8 weeks
Plasma CA19-9 levels	Change in plasma CA19-9 levels.	8 weeks
Disease Control	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.	8 weeks
Overall survival	Measurement of time from first dose of azeliragon until death from any cause.	8 weeks
Change in Eastern Cooperative Oncology Group (ECOG) status.	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.	8 weeks
Serum albumin	Change from baseline in serum albumin concentration.	8 weeks
Body Weight	Change from baseline in body weight.	8 weeks

Collaborators and Investigators

• Sponsor: Cantex Pharmaceuticals
• Investigators: Principal Investigator: Andrew Hendifar, MD, Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: February 24, 2023
• First Submitted That Met QC Criteria: March 10, 2023
• First Posted (Actual): March 13, 2023

Study Record Updates

• Last Update Posted (Actual): June 14, 2024
• Last Update Submitted That Met QC Criteria: June 13, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: azeliragon
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: CAN-201 MPC

Drug and device information, study documents

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