Azeliragon for Refractory Pancreatic Cancer
Recruiting in Palo Alto (17 mi)
+5 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
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
Trial Summary
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.
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.
12345Eligibility 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.
+5 more
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.
+6 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Treatment GroupExperimental Treatment1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Prisma Health - UpstateGreenville, SC
AHN Cancer Institute - Allegheny General HospitalPittsburgh, PA
Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer InstituteLos Angeles, CA
Boca Raton Regional Hospital, Lynn Cancer InstituteBoca Raton, FL
More Trial Locations
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Who Is Running the Clinical Trial?
Cantex PharmaceuticalsLead Sponsor
References
Evaluation of Efficacy of Radioimmunotherapy with 90Y-Labeled Fully Human Anti-Transferrin Receptor Monoclonal Antibody in Pancreatic Cancer Mouse Models. [2018]Pancreatic cancer is an aggressive tumor and the prognosis remains poor. Therefore, development of more effective therapy is needed. We previously reported that 89Zr-labeled TSP-A01, an antibody against transferrin receptor (TfR), is highly accumulated in a pancreatic cancer xenograft, but not in major normal organs. In the present study, we evaluated the efficacy of radioimmunotherapy (RIT) with 90Y-TSP-A01 in pancreatic cancer mouse models.
Pancreatic cancer: from state-of-the-art treatments to promising novel therapies. [2022]Pancreatic cancer is expected to be the second deadliest malignancy in the USA by 2020. The survival rates for patients with other gastrointestinal malignancies have increased consistently during the past 30 years; unfortunately, however, the outcomes of patients with pancreatic cancer have not changed significantly. Although surgery remains the only curative treatment for pancreatic cancer, therapeutic strategies based on initial resection have not substantially improved the survival of patients with resectable disease over the past 25 years; presently, more than 80% of patients suffer disease relapse after resection. Preclinical evidence that pancreatic cancer is a systemic disease suggests a possible benefit for early administration of systemic therapy in these patients. In locally advanced disease, the role of chemoradiotherapy is increasingly being questioned, particularly considering the results of the LAP-07 trial. Novel biomarkers are clearly needed to identify subsets of patients likely to benefit from chemoradiotherapy. In the metastatic setting, FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin), and nab-paclitaxel plus gemcitabine have yielded only modest improvements in survival. Thus, new treatments are urgently needed for patients with pancreatic cancer. Herein, we review the state-of-the-art of pancreatic cancer treatment, and the upcoming novel therapeutics that hold promise in this disease are also discussed.
Therapeutic evaluation of monoclonal antibody-maytansinoid conjugate as a model of RON-targeted drug delivery for pancreatic cancer treatment. [2020]Aberrant expression of the RON receptor tyrosine kinase, a member of the MET proto-oncogene family, contributes significantly to pancreatic cancer tumorigenesis and chemoresistance. Here we validate RON as a target for pancreatic cancer therapy using a novel anti-RON antibody Zt/g4-drug maytansinoid conjugates (Zt/g4-DM1) as a model for RON-targeted drug delivery to kill pancreatic cancer cells. In pancreatic cancer cell lines overexpressing RON, Zt/g4-DM1 rapidly induced receptor endocytosis, arrested cell cycle at G2/M phase, reduced cell viability, and subsequently caused massive cell death. These in vitro observations help to establish a correlation between the number of the cell surface RON receptors and the efficacy of Zt/g4-DM1 in reduction of cell viability. In mice, Zt/g4-DM1 pharmacokinetics in the linear dose range fitted into a two-compartment model with clearance in 0.21 ml/day/kg and terminal half-life at 6.05 days. These results helped to confirm a concentration-activity relationship for the BxPC-3 and other pancreatic cancer cell xenograft model with a tumoristatic dose at 3.02 mg/kg. Zt/g4-DM1 was effective in vivo against various xenograft PDAC growth but efficacy varied with individual cell lines. Combination of Zt/g4-DM1 with gemcitabine had a complete inhibition of xenograft pancreatic cancer growth. We conclude from these studies that increased RON expression in pancreatic cancer cells is a suitable targeting moiety for anti-RON ADC-directed drug delivery and anticancer therapy. Zt/g4-DM1 is highly effective alone or in combination with chemotherapeutics in inhibition of pancreatic cancer xenograft growth in preclinical models. These findings justify the use of humanized Zt/g4-DM1 for targeted pancreatic cancer therapy in the future.
Activation of GLP-1 receptor enhances the chemosensitivity of pancreatic cancer cells. [2022]This study aimed to determine whether and how the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide affects the chemoresistance and chemosensitivity of pancreatic cancer cells to gemcitabine in vitro and in vivo. The GLP-1R and protein kinase A (PKA) levels were compared between the human pancreatic cancer cell line PANC-1 and the gemcitabine-resistant cell line PANC-GR. The in vitro effects of liraglutide on the cell proliferation and apoptosis as well as the nuclear factor-kappa B NF-κB expression levels of PANC-GR cells were evaluated. In addition, a mouse xenograft model of human pancreatic cancer was established by s.c. injection of PANC-1 cells, and the effects of liraglutide on the chemosensitivity were evaluated in vitro and in vivo. In contrast to PANC-1 cells, PANC-GR cells exhibited lower expression levels of GLP-1R and PKA. Incubation with liraglutide dose dependently inhibited the growth, promoted the apoptosis, and increased the expression of GLP-1R and PKA of PANC-GR cells. Similar effects of liraglutide were observed in another human pancreatic cancer cell line MiaPaCa-2/MiaPaCa-2-GR. Either the GLP-1R antagonist Ex-9, the PKA inhibitor H89, or the NF-κB activator lipopolysaccharide (LPS) could abolish the antiproliferative and proapoptotic activities of liraglutide. Additionally, each of these agents could reverse the expression of NF-κB and ABCG2, which was decreased by liraglutide treatment. Furthermore, liraglutide treatment increased the chemosensitivity of pancreatic cancer cells to gemcitabine, as evidenced by in vitro and in vivo experiments. Thus, GLP-1R agonists are safe and beneficial for patients complicated with pancreatic cancer and diabetes, especially for gemcitabine-resistant pancreatic cancer.
A review of systemic therapy for advanced pancreatic cancer. [2007]Pancreatic cancer remains an important cause of cancer mortality with few long-term survivors. Improvement in the systemic therapy of pancreatic cancer is necessary to treat the frequently encountered metastatic disease. Several new chemotherapeutic agents with modest activity against pancreatic cancer have been identified over the past decade. Gemcitabine is currently the standard treatment for advanced pancreatic cancer. Combination chemotherapy trials incorporating gemcitabine, cisplatin, 5-fluorouracil, oxaliplatin, or irinotecan generally show improved outcomes in objective response rates but with little or no improvement in survival in phase III trials. Novel therapeutic strategies targeting dysregulated molecular pathways in pancreatic cancer cells are currently being explored. Future treatment regimens for pancreatic cancer will probably incorporate conventional cytotoxic drugs and novel targeted agents.