Pyrvinium Pamoate for Pancreatic Cancer

Overseen By Harish Lavu, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Thomas Jefferson University

Must not be taking: Anticancer therapies

Disqualifiers: Pregnancy, Chronic bowel conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 days

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing pyrvinium pamoate, a medication that may slow down the growth of pancreatic cancer. It targets patients whose cancer cannot be removed by surgery. The goal is to see if this treatment can help these patients live longer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on ongoing anticancer therapies or have received them within three weeks before starting the trial.

What makes pyrvinium pamoate unique as a drug for pancreatic cancer?

Pyrvinium pamoate is unique because it is originally an anti-parasitic drug that has shown potential in treating pancreatic cancer by targeting cancer cell metabolism, specifically inhibiting mitochondrial respiration and protein responses under low glucose conditions, which is different from traditional chemotherapy approaches. ^{1 2 3 4 5}

Research Team

Harish Lavu, MD

Principal Investigator

Thomas Jefferson University

Eligibility Criteria

This trial is for patients with pancreatic ductal adenocarcinoma that can't be surgically removed. Participants must not be on recent anticancer therapy, agree to use contraception, and have a life expectancy over 3 months with good performance status. Excluded are pregnant or breastfeeding individuals, those with chronic bowel conditions, kidney or liver function impairment.

Inclusion Criteria

Willing to comply with all study procedures and be available for the duration of the study

I haven't started neoadjuvant therapy or finished it at least 3 weeks before starting PP therapy.

I agree to use birth control during and for 30 days after the study.

Exclusion Criteria

My kidney function is impaired.

I am not currently on cancer treatment and haven't been for the last 3 weeks.

I have a long-term bowel condition like IBD.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pyrvinium pamoate orally once daily for 3 days, followed by standard of care surgery

3 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pyrvinium Pamoate

Trial Overview The study tests the safety and optimal dosage of Pyrvinium Pamoate (PP) in treating non-resectable pancreatic cancer. It aims to determine if PP can slow tumor growth and extend patient survival.

Participant Groups

Group I: Treatment (pyrvinium pamoate) Experimental Treatment 1 Intervention

Patients receive pyrvinium pamoate PO QD for 3 days in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery.

Pyrvinium Pamoate is already approved in United States for the following indications:

Approved in United States as Pyrvinium pamoate for:

• Anthelmintic for pinworms

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

Findings from Research

A phase I clinical trial is currently evaluating the safety and tolerability of pyrvinium pamoate (PP) in patients with pancreatic ductal adenocarcinoma (PDAC), with doses starting at 5 mg/kg and potentially increasing to 20 mg/kg before surgery.

The trial aims to assess not only the safety of PP but also its pharmacokinetic and pharmacodynamic profiles, which could support its use alongside chemotherapy in treating pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Ponzini, FM., Schultz, CW., Leiby, BE., et al.[2023]

Pyrvinium pamoate (PP) effectively inhibits the proliferation of B cell acute lymphoblastic leukemia (ALL) cells while sparing normal immune cells, indicating its potential as a targeted anti-leukemic treatment.

PP's mechanism of action involves inhibiting mitochondrial oxidative phosphorylation, and it can be successfully delivered using a nanoparticle system to enhance targeting in the hypoxic bone tumor microenvironment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pyrvinium Pamoate Use in a B cell Acute Lymphoblastic Leukemia Model of the Bone Tumor Microenvironment. Nair, RR., Piktel, D., Hathaway, QA., et al.[2022]

Pyrvinium pamoate (PP) shows promising anti-cancer effects, particularly against pancreatic cancer cells, by selectively targeting and killing cancer cells during glucose starvation and hypoxic conditions, as demonstrated in mouse models.

PP works by disrupting mitochondrial respiration, specifically inhibiting the NADH-fumarate reductase system and complex I of the electron transport chain, which leads to reduced ATP production and impaired cancer cell proliferation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reprofiling a classical anthelmintic, pyrvinium pamoate, as an anti-cancer drug targeting mitochondrial respiration. Ishii, I., Harada, Y., Kasahara, T.[2021]

Pyrvinium pamoate shows significant anti-tumor effects against myeloid leukemia by inducing an integrated stress response (ISR) and modulating mitochondrial function, as demonstrated in human AML cell lines and xenograft models.

The study revealed that pyrvinium triggers pathways related to endoplasmic reticulum stress and metabolic reprogramming, leading to reduced tumor growth in both standard and cabozantinib-resistant leukemia cell lines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deciphering the Role of Pyrvinium Pamoate in the Generation of Integrated Stress Response and Modulation of Mitochondrial Function in Myeloid Leukemia Cells through Transcriptome Analysis. Fu, YH., Tseng, CY., Lu, JW., et al.[2021]

Pyrvinium pamoate (PP) effectively inhibits the growth of human myeloma and erythroleukemia cells by targeting mitochondrial respiratory complex I and disrupting ATP production, which is crucial for cell proliferation.

PP also reduces phosphorylation of the STAT3 protein, a key factor in cancer cell survival, and shows a synergistic effect when combined with dexamethasone, suggesting its potential as an anticancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pyrvinium pamoate inhibits proliferation of myeloma/erythroleukemia cells by suppressing mitochondrial respiratory complex I and STAT3. Harada, Y., Ishii, I., Hatake, K., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

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. [2023]

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

Pyrvinium Pamoate Use in a B cell Acute Lymphoblastic Leukemia Model of the Bone Tumor Microenvironment. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Reprofiling a classical anthelmintic, pyrvinium pamoate, as an anti-cancer drug targeting mitochondrial respiration. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Deciphering the Role of Pyrvinium Pamoate in the Generation of Integrated Stress Response and Modulation of Mitochondrial Function in Myeloid Leukemia Cells through Transcriptome Analysis. [2021]

5. Ireland pubmed.ncbi.nlm.nih.gov

Pyrvinium pamoate inhibits proliferation of myeloma/erythroleukemia cells by suppressing mitochondrial respiratory complex I and STAT3. [2019]