Pyrvinium Pamoate for Pancreatic Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Thomas Jefferson University
Must not be taking: Anticancer therapies
Disqualifiers: Pregnancy, Chronic bowel conditions, others
No Placebo Group
Approved in 1 Jurisdiction
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.
12345Eligibility 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.
+5 more
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.
+5 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Treatment (pyrvinium pamoate)Experimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Thomas Jefferson UniversityPhiladelphia, PA
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Who Is Running the Clinical Trial?
Thomas Jefferson UniversityLead Sponsor
References
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]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.
Pyrvinium Pamoate Use in a B cell Acute Lymphoblastic Leukemia Model of the Bone Tumor Microenvironment. [2022]Pyrvinium pamoate (PP) is an anthelmintic drug that has been found to have anti-cancer activity in several cancer types. In the present study, we evaluated PP for potential anti-leukemic activity in B cell acute lymphoblastic leukemia (ALL) cell lines, in an effort to evaluate the repurposing potential of this drug in leukemia.
Reprofiling a classical anthelmintic, pyrvinium pamoate, as an anti-cancer drug targeting mitochondrial respiration. [2021]Pyrvinium pamoate (PP) is an FDA-approved classical anthelmintic, but is now attracting particular attention as an anti-cancer drug after recent findings of its potent cytotoxicity against various cancer cell lines only during glucose starvation, as well as its anti-tumor activity against hypovascular pancreatic cancer cells transplanted in mice. The molecular mechanisms by which PP promotes such preferential toxicity against cancer cells are currently under extensive investigation. PP suppressed the NADH-fumarate reductase system that mediates a reverse reaction of the mitochondrial electron-transport chain complex II in anaerobic organisms such as parasitic helminthes or mammalian cells under tumor microenvironment-mimicking hypoglycemic/hypoxic conditions, thereby inhibiting efficient ATP production. PP also inhibited the unfolded protein response induced by glucose starvation, thereby inhibiting the proliferation of pancreatic cancer cells. Even under normoglycemic/normoxic conditions, PP suppressed the mitochondrial electron-transport chain complex I and thereby STAT3, inhibiting the proliferation of myeloma/erythroleukemia cells. Here, we review accumulating knowledge on its working mechanisms and evaluate PP as a novel anti-cancer drug that targets mitochondrial respiration.
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]Pyrvinium pamoate, a widely-used anthelmintic agent, reportedly exhibits significant anti-tumor effects in several cancers. However, the efficacy and mechanisms of pyrvinium against myeloid leukemia remain unclear. The growth inhibitory effects of pyrvinium were tested in human AML cell lines. Transcriptome analysis of Molm13 myeloid leukemia cells suggested that pyrvinium pamoate could trigger an unfolded protein response (UPR)-like pathway, including responses to extracellular stimulus [p-value = 2.78 × 10-6] and to endoplasmic reticulum stress [p-value = 8.67 × 10-7], as well as elicit metabolic reprogramming, including sulfur compound catabolic processes [p-value = 2.58 × 10-8], and responses to a redox state [p-value = 5.80 × 10-5]; on the other hand, it could elicit a pyrvinium blunted protein folding function, including protein folding [p-value = 2.10 × 10-8] and an ATP metabolic process [p-value = 3.95 × 10-4]. Subsequently, pyrvinium was verified to induce an integrated stress response (ISR), demonstrated by activation of the eIF2α-ATF4 pathway and inhibition of mTORC1 signaling, in a dose- and time-dependent manner. Additionally, pyrvinium could co-localize with mitochondria and then decrease the mitochondrial basal oxidative consumption rate, ultimately dysregulating the mitochondrial function. Similar effects were observed in cabozantinib-resistant Molm13-XR cell lines. Furthermore, pyrvinium treatment retarded Molm13 and Molm13-XR xenograft tumor growth. Thus, we concluded that pyrvinium exerts anti-tumor activity, at least, via the modulation of the mitochondrial function and by triggering ISR.
Pyrvinium pamoate inhibits proliferation of myeloma/erythroleukemia cells by suppressing mitochondrial respiratory complex I and STAT3. [2019]Pyrvinium pamoate (PP), a classical anthelminthic, potently inhibited proliferation and STAT3 Tyr705 phosphorylation of human myeloma (U266B1 and PCM6)/erythroleukemia (HEL 92.1.7) cells. PCM6 cell proliferation was markedly impaired by STAT3 siRNA knockdown. PP inhibited ATP production/O(2) consumption in those three cells and mitochondrial respiratory complex (I+III, but not II+III) activity in mouse kidney mitochondrial fractions. PP inhibition of ATP production, STAT3 Tyr705 phosphorylation, and proliferation was absent in mitochondrial DNA-deficient HEL 92.1.7-ρ(0) cells. Moreover, PP acted synergistically with dexamethasone to inhibit PCM6 cell proliferation. In conclusion, we identified PP as a potential anticancer drug directed against mitochondrial respiratory complex I/STAT3.