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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Stage IB Pancreatic Cancer AJCC v8, Resectable Pancreatic Ductal Adenocarcinoma, Stage 0 Pancreatic Cancer AJCC v8, Stage I Pancreatic Cancer AJCC v8, Stage IA Pancreatic Cancer AJCC v8, Stage II Pancreatic Cancer AJCC v8, Stage IIA Pancreatic Cancer AJCC v8, Stage IIB Pancreatic Cancer AJCC v8

Intervention / Treatment
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* Drug: Pyrvinium Pamoate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (pyrvinium pamoate)<br>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<br>* Given PO<br>* Other names: 3546-41-6;|

What is the study measuring?
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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 |