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Cited by 15Pancreatic and Hepatic Oncology ResearchPancreatitis Pathology and TreatmentCancer Treatment and Pharmacology

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

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Ponzini, Francesca M, Schultz, Christopher W, Leiby, Benjamin E, Cannaday, Shawnna, Yeo, T, Posey, James, Bowne, Wilbur B, Yeo, Charles +3 more·2023·BMJ Open
DOI 10.1136/bmjopen-2023-073839PMC PMC10582846
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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 .

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Cited by

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Authors
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.
Affiliations
  • Thomas Jefferson University (US)
  • National Institutes of Health (US)
  • Oregon Health & Science University (US)
Corresponding author
Nevler, Avinoam
ORCID
Venue
BMJ Open
Publisher
BMJ
Published
2023-10
Volume
13
Issue
10
Pages
e073839
ISSN
2044-6055 (ISSN-L)
DOI
10.1136/bmjopen-2023-073839
PMC
PMC10582846
OpenAlex
W4387702106
Cited by
15
References
1
Citations by year
2026: 5 · 2025: 3 · 2024: 7
FWCI
1.83
Type
journal article
Language
en
Open access
Licence
Locations
  • BMJ Open (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (acceptedVersion)
  • The Medicine Forum (submittedVersion, cc-by-nc)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
Keywords
pyrvinium pamoate, pancreatic ductal adenocarcinoma, drug repurposing, anthelmintics, dose escalation, safety and tolerability, pharmacokinetics, pharmacodynamics, premedication, early-stage pancreatic cancer, combination chemotherapy
MeSH terms
Adenocarcinoma, Anthelmintics, Humans, Pancreatic Neoplasms, Pyrvinium Compounds, Clinical Trials, Phase I as Topic, Carcinoma, Pancreatic Ductal, Drug Repositioning

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