A Study to Determine if the Drug, Pyrvinium Pamoate, is Safe and Tolerable in Patients With Pancreatic Cancer

A Phase I Dose Escalation Study Using Pyrvinium Pamoate Targeting HuR in Pancreatic Ductal Adenocarcinoma

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 by surgery (resectable). Pyrvinium pamoate may slow down tumor growth and help patients live longer.

Study Overview

• Status: Recruiting
• Conditions: Stage II Pancreatic Cancer AJCC v8; Stage 0 Pancreatic Cancer AJCC v8; Stage I Pancreatic Cancer AJCC v8; Stage IA Pancreatic Cancer AJCC v8; Stage IB Pancreatic Cancer AJCC v8; Stage IIA Pancreatic Cancer AJCC v8; Stage IIB Pancreatic Cancer AJCC v8; Resectable Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Drug: Pyrvinium Pamoate

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the safety and tolerability of pyrvinium pamoate (PP), dosed orally, in patients with pancreatic ductal adenocarcinoma (PDAC) that are surgical candidates.

SECONDARY OBJECTIVE:

I. Assessment of PP's pharmacokinetic and pharmacodynamic (PK/PD) profile and bioavailability in humans.

OUTLINE: This is a dose-escalation study.

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

After completion of study treatment, patients are followed up for 30 days and then every week for up to 4 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Harish Lavu, MD; Phone Number: 215-955-9402; Email: harish.lavu@jefferson.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University
      • Contact: Harish Lavu, MD; Phone Number: 215-955-9402; Email: harish.lavu@jefferson.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with a diagnosis of pancreatic ductal adenocarcinoma (PDAC) suspected preoperatively who are deemed to be surgical candidates by the Thomas Jefferson University surgery department. Patients will be assessed by the pancreatic surgeons in the pancreatic surgery clinic, and if they are found to have resectable disease, they can be considered for this study
• Patients must not be on neoadjuvant therapy, or have received their last neoadjuvant treatment greater than or equal to within three weeks of starting PP therapy
• Provide signed and dated informed consent form
• Willing to comply with all study procedures and be available for the duration of the study
• Patients must have an estimated life expectancy of > 3 months, and Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

• All patients regardless of age or gender must agree to observe proper contraceptive methods as to avoid becoming pregnant or causing pregnancy for the duration of the study (30 days after last dose of drug)

  • Males will practice safe sex methods (i.e. condoms)
  • Women of child bearing potential will practice safe sex methods (i.e. condoms, birth control), if a female on the study is of child-bearing age, they will have to take a urine human chorionic gonadotropin (HCG) (pregnancy) test prior to enrolling on the study

Exclusion Criteria:

• Patients with ongoing anticancer therapies, or those who will have received an anticancer therapeutic <3 weeks prior to the first dose of PP
• Any condition that precludes pancreatic surgical resection at the time of the study
• Pregnancy or currently breastfeeding
• Known allergic reactions to components of the study product(s): pyrvinium pamoate/ pyrvinium embonate (Molevac)
• Patients with chronic bowel conditions (such as inflammatory bowel disease (IBD))
• Kidney function impairment (serum creatine > 1.5 x ULN or creatine clearance </= 60 ml/1.73m^2 fr patients with creatine levels > 1.5 x ULN).

• Patients with liver function impairment: Alkaline phosphatase, ALT and AST above three folds the normal limit (see normal ranges); Total Bilirubin level > 3mg/dl; Albumin < 3g/dl

  * Alkaline phosphatase:

  • 0-9 years (yr): 83-280 IU/L at 37 degrees Celsius
  • 10-14 yr: 91-400
  • 15-17 yr: 37-240
  • 18-49 yr: 29-92
  • 50-74 yr: 25-120
  • 75-97 yr: 29-160
  • 98-99 yr: 29-120
  • > 99 yr: 29-160

• Patients with liver function impairment outside of the below ranges

  * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]):

  ** Male (M): 1-45 IU/L at 37 degrees Celsius

  ** Female (F): 1-30

• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]):

  • M: 7-42 IU/L at 37 degrees Celsius
  • F: 7-35

• Patients with liver function impairment outside of the below ranges

  * Albumin:

  • 0-1 yr: 2.6-4.4
  • 1-15 yr: 3.0-4.7
  • 16-99 yr: 3.2-4.9

• Patients with liver function impairment outside of the below ranges

  * Bilirubin, total:

  ** 0.1-0.9 mg/dL

• Patients with liver function impairment outside of the below ranges * Protein, total:

  • 0-1 yr: 4.6-7.2 g/dL
  • 1-15 yr: 5.7-8.2
  • 16-99 yr: 6.0-8.5

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (pyrvinium pamoate); 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.	Drug: Pyrvinium Pamoate; Given PO; Other Names: 3546-41-6

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose limited toxicity (DLT)	Considered any grade 3 or higher adverse event due to the drug itself or delay of surgery. Research coordinator will call patient every day to monitor for DLTs.	Up to 30 days from last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Profile of pyrvinium pamoate (PP)	Will be assessed using liquid chromatography followed by mass spectrometry (LC/MS).	At Start of Treatment
Profile of pyrvinium pamoate (PP)	Will be assessed using liquid chromatography followed by mass spectrometry (LC/MS).	Completion of treatment
Bioavailability of PP	Will be assessed using liquid chromatography followed by mass spectrometry (LC/MS).	Up to 4 weeks
Fatty tissue accumulation of PP	Will be assessed using liquid chromatography followed by mass spectrometry (LC/MS).	Up to 4 weeks

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Investigators: Principal Investigator: Harish Lavu, MD, Thomas Jefferson University

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2021
• Primary Completion (Estimated): April 29, 2024
• Study Completion (Estimated): April 29, 2024

Study Registration Dates

• First Submitted: July 6, 2021
• First Submitted That Met QC Criteria: September 21, 2021
• First Posted (Actual): September 24, 2021

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Adenocarcinoma; Pancreatic Neoplasms; Anti-Infective Agents; Antiparasitic Agents; Anthelmintics; Pyrvinium
• Other Study ID Numbers: 20F.041

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No