Use of Celecoxib in Patients With Intraductal Papillary Mucinous Neoplasms (IPMNs)

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to find out whether the drug celecoxib has beneficial effects on people with pre-cancerous lesions of the pancreas.

Detailed Description
-----------------
Efforts at finding a successful chemotherapy for pancreatic cancer have been disappointing. Some patients are at increased risk of pancreatic cancer or may have pre-malignant pancreatic lesions which predispose them to later pancreatic cancer development. In these individuals, chemopreventative measures may block future development of pancreatic cancer. Human tissue studies, cell culture and animal models of pancreatic cancer strongly suggests that cyclooxygenase-2 (COX-2) may be a successful target for chemoprevention. COX-2 is overexpressed in human pancreatic cancers. Elevated COX-2 expression correlates with progression of premalignant precursors of pancreatic cancer in development models of hamster pancreatic cancer. Human tissue studies confirm increases in COX-2 expression with progression of premalignant precursors called intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasms (PanINs). Moreover, COX-2 inhibitors appear to have chemopreventative efficacy in the PC-1 homograft model of hamster pancreatic cancer. Demographic studies have suggested COX-2 inhibitors may confer protection from pancreatic cancer. We propose to conduct a pilot/phase II trial to determine the chemopreventative effects of the COX-2 inhibitor celecoxib in patients with premalignant pancreatic lesions. Patients registered to the study will take celecoxib twice daily for 6-8 weeks prior to surgery (if patient decides to have surgery for his/her condition). If subject is not a surgical candidate or puts off surgical treatment, subject will take celecoxib for 6 months.

Official Title
-----------------
A Phase II Trial of Celecoxib in Patients With IPMN

Conditions
-----------------
Pancreas Neoplasms

Intervention / Treatment
-----------------
* Drug: COX-2 Inhibitor 6-8 weeks prior to surgery
* Drug: COX-2 Inhibitor for 6 months prior to follow-up EUS or ERCP


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinical diagnosis of IPMN ECOG Performance status of 0, 1, or 2 Adequate liver function, bilirubin < 1.5 times ULN, ALT or AST < 2.5 times ULN Adequate renal function: creatinine < 1.8 Must be at least 18 Exclusion Criteria: Use of COX-2 selective inhibitors within the last month More than occasional use of NSAIDS in last month (occasional use defined as up to twice weekly dosing) CA19-9 levels 1.5 times the ULN Active pancreatitis Taking sulphonylureas, fluconazole or lithium concomitantly

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Surgical Candidate<br>COX-2 Inhibitor 6-8 weeks prior to surgery | Drug: COX-2 Inhibitor 6-8 weeks prior to surgery<br>* 400 mg BID 6-8 weeks prior to surgery<br>* Other names: Celecoxib;|
| Experimental: Medical Candidate<br>COX-2 Inhibitor for 6 months prior to follow-up EUS or ERCP | Drug: COX-2 Inhibitor for 6 months prior to follow-up EUS or ERCP<br>* 400 mg BID for 6 months prior to follow-up EUS or ERCP<br>* Other names: Celecoxib;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | Measured by Elisa at participant level - only participant level data available; not summarized across group | Baseline, surgery, 1 wk, 4 wks, and 6 months | 
| Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | Measured by Elisa at participant level - only participant level data available; not summarized across group | Baseline, surgery, 1 wk, 4 wks, and 6 months | 
| Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | Measured by Elisa at participant level - only participant level data available; not summarized across group | Baseline, surgery, 1 wk, 4 wks, and 6 months | 
| Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | Measured by Elisa at participant level - only participant level data available; not summarized across group | Baseline, surgery, 1 wk, 4 wks, and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Changes in IPMN Progression. | Examine the short term effect of celecoxib on clinical progression of IPMN in the surgical arm; Examine the long term effect of celecoxib on clinical progression of IPMN in the medical arm. | Baseline, 6 months, 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
celecoxib for pancreas lesions