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
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, si...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2023-10-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/13/10/e073839.full |
| _version_ | 1827121664212598784 |
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| author | Benjamin E Leiby Charles Yeo James Posey Avinoam Nevler Harish Lavu T Yeo Francesca M Ponzini Christopher W Schultz Shawnna Cannaday Wilbur B Bowne Jonathan R Brody |
| author_facet | Benjamin E Leiby Charles Yeo James Posey Avinoam Nevler Harish Lavu T Yeo Francesca M Ponzini Christopher W Schultz Shawnna Cannaday Wilbur B Bowne Jonathan R Brody |
| author_sort | Benjamin E Leiby |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T10:46:14Z |
| format | Article |
| id | doaj.art-ae296dbfef724c018657b0a81258e828 |
| institution | Directory Open Access Journal |
| issn | 2044-6055 |
| language | English |
| last_indexed | 2025-03-20T13:56:44Z |
| publishDate | 2023-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj.art-ae296dbfef724c018657b0a81258e8282024-09-11T18:35:11ZengBMJ Publishing GroupBMJ Open2044-60552023-10-01131010.1136/bmjopen-2023-073839Repurposing the FDA-approved anthelmintic pyrvinium pamoate for pancreatic cancer treatment: study protocol for a phase I clinical trial in early-stage pancreatic ductal adenocarcinomaBenjamin E Leiby0Charles Yeo1James Posey2Avinoam Nevler3Harish Lavu4T Yeo5Francesca M Ponzini6Christopher W Schultz7Shawnna Cannaday8Wilbur B Bowne9Jonathan R Brody10Sidney Kimmel Medical College, Department of Pharmacology and Experimental Therapeutics, Division of Biostatistics, Thomas Jefferson University, Philadelphia, Pennsylvania, USADepartment of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USAJefferson Pancreatic, Biliary and Related Cancer Center, Sidney Kimmel Cancer Center, Philadelphia, Pennsylvania, USADepartment of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USAJefferson Pancreatic, Biliary and Related Cancer Center, Sidney Kimmel Cancer Center, Philadelphia, Pennsylvania, USADepartment of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USADepartment of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USACenter for Cancer Research, National Institutes of Health, Bethesda, Maryland, USADepartment of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USADepartment of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USABrenden Colson Center for Pancreatic Care; Departments of Surgery and Cell, Developmental & Cancer Biology, Oregon Health & Science University (OHSU), Portland, Oregon, USABackground 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.https://bmjopen.bmj.com/content/13/10/e073839.full |
| spellingShingle | Benjamin E Leiby Charles Yeo James Posey Avinoam Nevler Harish Lavu T Yeo Francesca M Ponzini Christopher W Schultz Shawnna Cannaday Wilbur B Bowne Jonathan R Brody 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://bmjopen.bmj.com/content/13/10/e073839.full |
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