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

Trial Summary

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.

How is the drug Azeliragon different from other treatments for pancreatic cancer?

Azeliragon is unique because it targets the receptor for advanced glycation end-products (RAGE), which is involved in inflammation and cancer progression, offering a novel approach compared to standard chemotherapy options like gemcitabine. ^{1 2 3 4 5}

What is the purpose of this trial?

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.

Research Team

Andrew Hendifar, MD

Principal Investigator

Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. United States 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. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Pancreatic cancer: from state-of-the-art treatments to promising novel therapies. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Therapeutic evaluation of monoclonal antibody-maytansinoid conjugate as a model of RON-targeted drug delivery for pancreatic cancer treatment. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Activation of GLP-1 receptor enhances the chemosensitivity of pancreatic cancer cells. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

A review of systemic therapy for advanced pancreatic cancer. [2007]