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

Phase 2

Terminated

Conditions: Pancreas Neoplasms

Interventions: Drug: COX-2 Inhibitor 6-8 weeks prior to surgery
Drug: COX-2 Inhibitor for 6 months prior to follow-up EUS or ERCP

Registration Number: NCT00198081

Lead Sponsor: Indiana University School of Medicine

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 8

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Surgical Candidate	COX-2 Inhibitor 6-8 weeks prior to surgery	COX-2 Inhibitor 6-8 weeks prior to surgery
Medical Candidate	COX-2 Inhibitor for 6 months prior to follow-up EUS or ERCP	COX-2 Inhibitor for 6 months prior to follow-up EUS or ERCP

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Clinical Changes in IPMN Progression.	Baseline, 6 months, 1 year	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.