Azeliragon for Refractory Pancreatic Cancer

Recruiting at 5 trial locations

Overseen By Stephen Marcus, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Cantex Pharmaceuticals

Must not be taking: CYP 2C8 inhibitors

Disqualifiers: Life expectancy < 3 months, uncontrolled infections, serious medical or psychiatric illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called azeliragon for individuals with metastatic pancreatic cancer unresponsive to other treatments. The trial aims to determine azeliragon's safety and potential effectiveness in treating this challenging condition. Participants will receive varying doses to identify the safest and most effective one. Suitable candidates have advanced pancreatic cancer and have previously undergone treatments like Gemcitabine/Abraxane or FOLFIRINOX. This trial offers a new approach for those whose standard treatments have failed. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot take CYP 2C8 inhibitors while participating. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that azeliragon is likely to be safe for humans?

Research has shown that azeliragon has been tested in over 2,000 patients with Alzheimer's disease, demonstrating promising safety results. It was generally well-tolerated and did not cause major side effects in those studies. Additionally, the FDA has granted azeliragon "orphan drug designation" for treating pancreatic cancer, indicating early evidence of potential safety and efficacy. While specific safety results for pancreatic cancer are not detailed, the extensive safety data from Alzheimer's studies suggest it is likely safe for use in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Azeliragon for refractory pancreatic cancer because it offers a unique approach compared to standard treatments like chemotherapy and targeted therapies. Azeliragon targets the RAGE (Receptor for Advanced Glycation End-products) pathway, which plays a role in inflammation and cancer progression, offering a novel mechanism of action. This oral medication has the potential to improve outcomes by specifically targeting pathways not addressed by existing therapies, providing new hope for patients with limited treatment options.

What evidence suggests that azeliragon might be an effective treatment for pancreatic cancer?

Research suggests that azeliragon, the investigational treatment in this trial, might help treat pancreatic cancer by blocking signals that promote cancer growth. It shows promise as a cancer-fighting drug by influencing the immune system. Azeliragon aims to assist when other treatments fail, addressing a major challenge in treating pancreatic cancer. Studies have also found that it can enhance the effectiveness of radiation therapy against pancreatic cancer cells. Additionally, the FDA has granted it orphan drug status for pancreatic cancer, highlighting its potential in this difficult-to-treat disease. ^{1 2 6 7 8}

Who Is on the Research Team?

Andrew Hendifar, MD

Principal Investigator

Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with advanced or metastatic pancreatic cancer that can't be cured by surgery. They must have tried Gemcitabine/Abraxane or FOLFIRINOX treatments and recovered from previous chemo effects, except hair loss. Participants need normal blood counts and organ function, not be pregnant or breastfeeding, willing to use contraception, and able to swallow pills.

Inclusion Criteria

Your blood tests show that you have enough white blood cells, platelets, and hemoglobin.

I have been treated with Gemcitabine/Abraxane or FOLFIRINOX.

My liver and kidney functions are within the required ranges for the study.

Exclusion Criteria

I am willing to use effective birth control during and 6 months after the trial.

I have a stomach or intestine condition that affects my swallowing or digestion.

Patient has a life expectancy, per investigator assessment, of less than 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive azeliragon with dose escalation across 5 groups, starting with a loading dose followed by a maintenance dose

8 weeks

Weekly visits for dose escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Azeliragon

Trial Overview The study tests Azeliragon's safety and potential effectiveness in patients whose metastatic pancreatic cancer didn't respond to first-line or second-line treatments. It's an open-label trial where everyone knows they're getting the drug; there’s no placebo group.

How Is the Trial Designed?

Group I: Treatment Group Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Cantex Pharmaceuticals

Lead Sponsor

Trials

14

Recruited

390+

Published Research Related to This Trial

The anti-RON antibody Zt/g4-DM1 effectively targets pancreatic cancer cells that overexpress the RON receptor, leading to significant cell death and reduced viability in vitro, indicating its potential as a targeted therapy.

In preclinical models, Zt/g4-DM1 demonstrated strong efficacy against pancreatic cancer xenografts, especially when combined with gemcitabine, suggesting it could enhance treatment outcomes for patients with this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic evaluation of monoclonal antibody-maytansinoid conjugate as a model of RON-targeted drug delivery for pancreatic cancer treatment. Yao, HP., Feng, L., Zhou, JW., et al.[2020]

The study demonstrated that 90Y-TSP-A01, a radioimmunotherapy targeting the transferrin receptor, resulted in nearly complete tumor regression in MIAPaCa-2 pancreatic cancer models, indicating its potential efficacy as a treatment.

In contrast, while 90Y-TSP-A01 inhibited the growth of BxPC-3 tumors, it did not reduce their size, suggesting that further research is needed to enhance treatment effectiveness for more resistant pancreatic cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Efficacy of Radioimmunotherapy with 90Y-Labeled Fully Human Anti-Transferrin Receptor Monoclonal Antibody in Pancreatic Cancer Mouse Models. Sugyo, A., Tsuji, AB., Sudo, H., et al.[2018]

Liraglutide, a GLP-1 receptor agonist, enhances the sensitivity of gemcitabine-resistant pancreatic cancer cells to chemotherapy by promoting apoptosis and inhibiting cell growth, as shown in both in vitro and in vivo studies.

The study found that liraglutide increases the expression of GLP-1R and PKA in resistant cancer cells, and its effects can be reversed by blocking these pathways, indicating a specific mechanism of action that could benefit patients with pancreatic cancer and diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activation of GLP-1 receptor enhances the chemosensitivity of pancreatic cancer cells. Zhao, HJ., Jiang, X., Hu, LJ., et al.[2022]

Pancreatic cancer remains one of the deadliest cancers, with survival rates not improving significantly over the past 25 years, and over 80% of patients experience disease relapse after surgical resection.

Current treatments like FOLFIRINOX and nab-paclitaxel plus gemcitabine offer only modest survival benefits, highlighting the urgent need for new therapeutic strategies and biomarkers to better target treatment for pancreatic cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic cancer: from state-of-the-art treatments to promising novel therapies. Garrido-Laguna, I., Hidalgo, M.[2022]

Gemcitabine remains the standard treatment for advanced pancreatic cancer, but combination therapies with other chemotherapeutic agents have shown improved response rates without significantly extending survival, based on recent phase III trials.

Research is ongoing into novel therapies that target specific molecular pathways in pancreatic cancer cells, suggesting that future treatments may combine traditional chemotherapy with these new targeted approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of systemic therapy for advanced pancreatic cancer. El-Rayes, BF., Philip, PA.[2007]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11718873/

The RAGE Inhibitor TTP488 (Azeliragon) Demonstrates ... These findings suggest that Azeliragon, by inhibiting RAGE-mediated signaling and modulating immune response, may serve as an effective anti-cancer agent in ...

2. onclive.com onclive.com/view/fda-grants-orphan-drug-designation-to-azeliragon-for-pancreatic-cancer

FDA Grants Orphan Drug Designation to Azeliragon for ... The FDA has granted orphan drug designation to azeliragon (TTP488) as a potential therapeutic option for patients with pancreatic cancer.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39796649/

The RAGE Inhibitor TTP488 (Azeliragon) Demonstrates Anti ... Azeliragon, by inhibiting RAGE-mediated signaling and modulating immune response, may serve as an effective anti-cancer agent in pancreatic cancer.

4. mmehb.scholasticahq.com mmehb.scholasticahq.com/api/v1/articles/141486-the-rage-inhibitor-ttp488-azeliragon-demonstrates-anti-tumor-activity-and-enhances-the-efficacy-of-radiation-therapy-in-pancreatic-cancer.pdf

The RAGE Inhibitor TTP488 (Azeliragon) Demonstrates ... Introduction: Pancreatic cancer has a poor prognosis, with a 5-year survival rate below. 10%, and is projected to become the 2nd leading cause of ...

5. semanticscholar.org semanticscholar.org/paper/Overcoming-therapy-resistance-in-pancreatic-cancer%3A-Espona-Fiedler-Patthey/85b2f7691ae43e6e13d6128c36f42f5dee9970ba

[PDF] Overcoming therapy resistance in pancreatic cancer The RAGE Inhibitor TTP488 (Azeliragon) Demonstrates Anti-Tumor Activity and Enhances the Efficacy of Radiation Therapy in Pancreatic Cancer Cell Lines · K ...

6. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT05766748/

Trial | NCT05766748 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 ...

7. targetedonc.com targetedonc.com/view/fda-grants-orphan-drug-designation-to-azeliragon-for-patients-with-glioblastoma

FDA Grants Orphan Drug Designation to Azeliragon for ... In previous trials which evaluated azeliragon in over 2000 patients with Alzheimer's, clinical safety data were promising and showed the agent ...

8. researchgate.net researchgate.net/scientific-contributions/Stephen-Garrett-Marcus-2252947647

Stephen Garrett Marcus's research works | Cantex ... Azeliragon has extensive clinical safety data in patients ... azeliragon in patients refractory to first-line treatment of metastatic pancreatic cancer.