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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pyrvinium pamoate, a potential cancer treatment, to determine the optimal dose and identify side effects for treating pancreatic ductal adenocarcinoma, a type of pancreatic cancer that cannot be surgically removed. The goal is to assess whether this treatment can slow tumor growth and extend patient survival. Patients with operable pancreatic cancer, who have not recently undergone certain cancer treatments, may be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that pyrvinium pamoate is likely to be safe for humans?

Research shows that pyrvinium pamoate is undergoing tests for safety and patient tolerance in pancreatic cancer cases. The FDA has already approved this drug for other uses, suggesting potential safety. Studies have found that pyrvinium pamoate can target and stop cancer cells. However, researchers are still gathering detailed safety information specifically for pancreatic cancer patients.

As a phase 1 trial, the main goal is to determine safe dosage levels and observe any side effects. Although some safety data exists from its use in other conditions, researchers are closely monitoring its effects on pancreatic cancer patients to ensure safety. Participants in these trials contribute valuable information about the treatment's safety and effectiveness for this specific type of cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pancreatic cancer?

Pyrvinium Pamoate is unique because it targets pancreatic cancer cells differently than most existing treatments. While standard therapies like chemotherapy typically attack rapidly dividing cells, Pyrvinium Pamoate disrupts the cancer cells' energy production, essentially starving them. This novel mechanism has researchers excited because it could potentially overcome resistance to traditional treatments and work faster, with results in just a few days. Plus, it's taken orally, which might be more convenient and less invasive for patients compared to conventional methods.

What evidence suggests that pyrvinium pamoate might be an effective treatment for pancreatic cancer?

Research has shown that pyrvinium pamoate, the treatment under study in this trial, may help combat pancreatic cancer. It targets the mitochondria, the energy centers of cells, particularly when nutrients are scarce, potentially slowing cancer cell growth. Lab tests in cells and animals suggest it could be a potent anti-cancer treatment. Although research in humans continues, these early results are promising for its potential use against pancreatic cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Harish Lavu, MD

Principal Investigator

Thomas Jefferson University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 (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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10582846/

Repurposing the FDA-approved anthelmintic pyrvinium ... 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05055323

A Study to Determine if the Drug, Pyrvinium Pamoate, is ... This phase I trial studies the side effects and best dose of pyrvinium pamoate for the treatment of pancreatic ductal adenocarcinoma that cannot be removed ...

3. aacrjournals.org aacrjournals.org/mct/article/doi/10.1158/1535-7163.MCT-20-0652/673497/p/The-FDA-Approved-Anthelmintic-Pyrvinium-Pamoate

The FDA-Approved Anthelmintic Pyrvinium Pamoate Inhibits ... The FDA-Approved Anthelmintic Pyrvinium Pamoate Inhibits Pancreatic Cancer Cells in Nutrient-Depleted Conditions by Targeting the Mitochondria Available.

4. mdpi.com mdpi.com/2227-9059/10/12/3249

Pyrvinium Pamoate: Past, Present, and Future as an Anti- ... Over the past two decades, increasing evidence has emerged showing pyrvinium to be a strong anti-cancer molecule in various human cancers in vitro and in vivo.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8859979/

The FDA approved anthelmintic Pyrvinium Pamoate inhibits ... The FDA approved anthelmintic Pyrvinium Pamoate inhibits pancreatic cancer cells in nutrient depleted conditions by targeting the mitochondria.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37848297/

study protocol for a phase I clinical trial in early-stage ... 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 ...

7. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05055323/a-study-to-determine-if-the-drug-pyrvinium-pamoate-is-safe-and-tolerable-in-patients-with-pancreatic-cancer

A Study to Determine if the Drug, Pyrvinium Pamoate, is ... This phase I trial studies the side effects and best dose of pyrvinium pamoate for the treatment of pancreatic ductal adenocarcinoma that ...