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
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19107
- Thomas Jefferson University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
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)
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.
|
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Incidence of dose limited toxicity (DLT)
Time Frame: Up to 30 days from last dose
|
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.
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Up to 30 days from last dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Profile of pyrvinium pamoate (PP)
Time Frame: At Start of Treatment
|
Will be assessed using liquid chromatography followed by mass spectrometry (LC/MS).
|
At Start of Treatment
|
|
Profile of pyrvinium pamoate (PP)
Time Frame: Completion of treatment
|
Will be assessed using liquid chromatography followed by mass spectrometry (LC/MS).
|
Completion of treatment
|
|
Bioavailability of PP
Time Frame: Up to 4 weeks
|
Will be assessed using liquid chromatography followed by mass spectrometry (LC/MS).
|
Up to 4 weeks
|
|
Fatty tissue accumulation of PP
Time Frame: Up to 4 weeks
|
Will be assessed using liquid chromatography followed by mass spectrometry (LC/MS).
|
Up to 4 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Harish Lavu, MD, Thomas Jefferson University
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 20F.041
- JT 14689 (Other Identifier: JeffTrial Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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