Repurposing the FDA-approved anthelmintic pyrvinium pamoate for pancreatic cancer treatment: study protocol for a phase I clinical trial in early-stage pancreatic ductal adenocarcinoma.

Authors

• Francesca M Ponzini
• Christopher W Schultz
• Benjamin E Leiby
• Shawnna Cannaday
• T Yeo
• James Posey
• Wilbur B Bowne
• Charles Yeo
• Jonathan R Brody
• Harish Lavu
• Avinoam Nevler

Publication/Presentation Date

10-17-2023

Abstract

BACKGROUND: Recent reports of the utilisation of pyrvinium pamoate (PP), an FDA-approved anti-helminth, have shown that it inhibits pancreatic ductal adenocarcinoma (PDAC) cell growth and proliferation in-vitro and in-vivo in preclinical models. Here, we report about an ongoing phase I open-label, single-arm, dose escalation clinical trial to determine the safety and tolerability of PP in PDAC surgical candidates.

METHODS AND ANALYSIS: In a 3+3 dose design, PP is initiated 3 days prior to surgery. The first three patients will be treated with the initial dose of PP at 5 mg/kg orally for 3 days prior to surgery. Dose doubling will be continued to a reach a maximum of 20 mg/kg orally for 3 days, if the previous two dosages (5 mg/kg and 10 mg/kg) were tolerated. Dose-limiting toxicity grade≥3 is used as the primary endpoint. The pharmacokinetic and pharmacodynamic (PK/PD) profile of PP and bioavailability in humans will be used as the secondary objective. Each participant will be monitored weekly for a total of 30 days from the final dose of PP for any side effects. The purpose of this clinical trial is to examine whether PP is safe and tolerable in patients with pancreatic cancer, as well as assess the drug's PK/PD profile in plasma and fatty tissue. Potential implications include the utilisation of PP in a synergistic manner with chemotherapeutics for the treatment of pancreatic cancer.

ETHICS AND DISSEMINATION: This study was approved by the Thomas Jefferson Institutional Review Board. The protocol number for this study is 20F.041 (Version 3.1 as of 27 October 2021). The data collected and analysed from this study will be used to present at local and national conferences, as well as, written into peer-reviewed manuscript publications.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT05055323.

Volume

13

Issue

10

First Page

073839

Last Page

073839

ISSN

2044-6055

Published In/Presented At

Ponzini, F. M., Schultz, C. W., Leiby, B. E., Cannaday, S., Yeo, T., Posey, J., Bowne, W. B., Yeo, C., Brody, J. R., Lavu, H., & Nevler, A. (2023). Repurposing the FDA-approved anthelmintic pyrvinium pamoate for pancreatic cancer treatment: study protocol for a phase I clinical trial in early-stage pancreatic ductal adenocarcinoma. BMJ open, 13(10), e073839. https://doi.org/10.1136/bmjopen-2023-073839

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

37848297

Department(s)

Administration and Leadership

Document Type

Article