Pancreas Neoplasms
Conditions
Keywords
celecoxib for pancreas lesions
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.
Interventions
DRUGCOX-2 Inhibitor 6-8 weeks prior to surgery
400 mg BID 6-8 weeks prior to surgery
DRUGCOX-2 Inhibitor for 6 months prior to follow-up EUS or ERCP
400 mg BID for 6 months prior to follow-up EUS or ERCP
Sponsors
Indiana University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Surgical Candidate COX-2 Inhibitor 6-8 weeks prior to surgery
COX-2 Inhibitor 6-8 weeks prior to surgery: 400 mg BID 6-8 weeks prior to surgery | 5 |
| 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: 400 mg BID for 6 months prior to follow-up EUS or ERCP | 0 |
| Total | 5 |
Baseline characteristics
| Characteristic | Surgical Candidate | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 participants | 0 participants |
| Age, Categorical >=65 years | 3 participants | 3 participants |
| Age, Categorical Between 18 and 65 years | 2 participants | 2 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 participants | 0 participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 participants | 5 participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 participants | 0 participants |
| Gender Female | 0 participants | 0 participants |
| Gender Male | 5 participants | 5 participants |
| IPMN type Adenoma | 1 participants | 1 participants |
| IPMN type Invasive | 1 participants | 1 participants |
| IPMN type Low grade | 1 participants | 1 participants |
| IPMN type Not Otherwise Specified | 1 participants | 1 participants |
| IPMN type Unknown | 1 participants | 1 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 participants | 0 participants |
| Race (NIH/OMB) Asian | 0 participants | 0 participants |
| Race (NIH/OMB) Black or African American | 0 participants | 0 participants |
| Race (NIH/OMB) More than one race | 0 participants | 0 participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 participants | 1 participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 participants | 0 participants |
| Race (NIH/OMB) White | 4 participants | 4 participants |
| Region of Enrollment United States | 5 participants | 5 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 5 | 0 / 0 |
| serious Total, serious adverse events | 2 / 5 | 0 / 0 |
Outcome results
Primary
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
Time frame: Baseline, surgery, 1 wk, 4 wks, and 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Surgical Candidate Baseline | Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Adenoma-Part 1 | 60 pg/ml |
| Surgical Candidate Baseline | Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN low-Part 2 | 170 pg/ml |
| Surgical Candidate Baseline | Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Invasive-Part 3 | 70 pg/ml |
| Surgical Candidate Baseline | Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN NOS-Part 4 | 100 pg/ml |
| Surgery Candidate Surgery | Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Adenoma-Part 1 | 70 pg/ml |
| Surgery Candidate Surgery | Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN NOS-Part 4 | 140 pg/ml |
| Surgery Candidate Surgery | Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN low-Part 2 | 90 pg/ml |
| Surgery Candidate Surgery | Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Invasive-Part 3 | 30 pg/ml |
| Surgical Candidate One Week | Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN NOS-Part 4 | 20 pg/ml |
| Surgical Candidate One Week | Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN low-Part 2 | 10 pg/ml |
| Surgical Candidate One Week | Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Invasive-Part 3 | 60 pg/ml |
| Surgical Candidate One Week | Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Adenoma-Part 1 | 70 pg/ml |
| Surgical Candidate 4 Weeks | Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Adenoma-Part 1 | 130 pg/ml |
| Surgical Candidate 4 Weeks | Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN low-Part 2 | 40 pg/ml |
| Surgical Candidate 4 Weeks | Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN NOS-Part 4 | 80 pg/ml |
| Surgical Candidate 4 Weeks | Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Invasive-Part 3 | 10 pg/ml |
| Surgical Candidate 6 Months | Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN NOS-Part 4 | 30 pg/ml |
| Surgical Candidate 6 Months | Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Invasive-Part 3 | 70 pg/ml |
| Surgical Candidate 6 Months | Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN low-Part 2 | 10 pg/ml |
| Surgical Candidate 6 Months | Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Adenoma-Part 1 | 100 pg/ml |
Primary
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
Time frame: Baseline, surgery, 1 wk, 4 wks, and 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Surgical Candidate Baseline | Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Invasive-Part 3 | 800 pg/ml |
| Surgical Candidate Baseline | Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Adenoma-Part 1 | 11800 pg/ml |
| Surgical Candidate Baseline | Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN low-Part 2 | 21000 pg/ml |
| Surgical Candidate Baseline | Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN NOS-Part 4 | 10100 pg/ml |
| Surgery Candidate Surgery | Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN low-Part 2 | 13400 pg/ml |
| Surgery Candidate Surgery | Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Adenoma-Part 1 | 13300 pg/ml |
| Surgery Candidate Surgery | Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN NOS-Part 4 | 8700 pg/ml |
| Surgery Candidate Surgery | Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Invasive-Part 3 | 30000 pg/ml |
| Surgical Candidate One Week | Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Adenoma-Part 1 | 12100 pg/ml |
| Surgical Candidate One Week | Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN NOS-Part 4 | 9500 pg/ml |
| Surgical Candidate One Week | Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN low-Part 2 | 4700 pg/ml |
| Surgical Candidate One Week | Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Invasive-Part 3 | 15400 pg/ml |
| Surgical Candidate 4 Weeks | Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Adenoma-Part 1 | 19600 pg/ml |
| Surgical Candidate 4 Weeks | Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN NOS-Part 4 | 40300 pg/ml |
| Surgical Candidate 4 Weeks | Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Invasive-Part 3 | 24800 pg/ml |
| Surgical Candidate 4 Weeks | Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN low-Part 2 | 36300 pg/ml |
| Surgical Candidate 6 Months | Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN NOS-Part 4 | 7500 pg/ml |
| Surgical Candidate 6 Months | Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Adenoma-Part 1 | 24000 pg/ml |
| Surgical Candidate 6 Months | Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN low-Part 2 | 16000 pg/ml |
| Surgical Candidate 6 Months | Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Invasive-Part 3 | 3600 pg/ml |
Primary
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
Time frame: Baseline, surgery, 1 wk, 4 wks, and 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Surgical Candidate Baseline | Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Adenoma-Part 1 | 20 pg/ml |
| Surgical Candidate Baseline | Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN NOS-Part 4 | 9 pg/ml |
| Surgical Candidate Baseline | Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Invasive-Part 3 | 2 pg/ml |
| Surgical Candidate Baseline | Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN low-Part 2 | 7 pg/ml |
| Surgery Candidate Surgery | Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN NOS-Part 4 | 3.4 pg/ml |
| Surgery Candidate Surgery | Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN low-Part 2 | 4.3 pg/ml |
| Surgery Candidate Surgery | Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Adenoma-Part 1 | 4 pg/ml |
| Surgery Candidate Surgery | Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Invasive-Part 3 | 3 pg/ml |
| Surgical Candidate One Week | Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Invasive-Part 3 | 11.8 pg/ml |
| Surgical Candidate One Week | Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Adenoma-Part 1 | 6.4 pg/ml |
| Surgical Candidate One Week | Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN NOS-Part 4 | 7.2 pg/ml |
| Surgical Candidate One Week | Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN low-Part 2 | 9.3 pg/ml |
| Surgical Candidate 4 Weeks | Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Invasive-Part 3 | 5.1 pg/ml |
| Surgical Candidate 4 Weeks | Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN low-Part 2 | 5.9 pg/ml |
| Surgical Candidate 4 Weeks | Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Adenoma-Part 1 | 5.4 pg/ml |
| Surgical Candidate 4 Weeks | Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN NOS-Part 4 | 4.3 pg/ml |
| Surgical Candidate 6 Months | Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN NOS-Part 4 | 1.8 pg/ml |
| Surgical Candidate 6 Months | Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Adenoma-Part 1 | 6.7 pg/ml |
| Surgical Candidate 6 Months | Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN low-Part 2 | 8.7 pg/ml |
| Surgical Candidate 6 Months | Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Invasive-Part 3 | 8.3 pg/ml |
Primary
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
Time frame: Baseline, surgery, 1 wk, 4 wks, and 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Surgical Candidate Baseline | Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Adenoma-Part 1 | 196 pg/ml |
| Surgical Candidate Baseline | Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN low-Part 2 | 257 pg/ml |
| Surgical Candidate Baseline | Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Invasive-Part 3 | 128 pg/ml |
| Surgical Candidate Baseline | Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN NOS-Part 4 | 131 pg/ml |
| Surgery Candidate Surgery | Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Adenoma-Part 1 | 177 pg/ml |
| Surgery Candidate Surgery | Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN NOS-Part 4 | 100 pg/ml |
| Surgery Candidate Surgery | Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN low-Part 2 | 201 pg/ml |
| Surgery Candidate Surgery | Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Invasive-Part 3 | NA pg/ml |
| Surgical Candidate One Week | Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN NOS-Part 4 | 184 pg/ml |
| Surgical Candidate One Week | Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN low-Part 2 | 153 pg/ml |
| Surgical Candidate One Week | Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Invasive-Part 3 | 850 pg/ml |
| Surgical Candidate One Week | Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Adenoma-Part 1 | 354 pg/ml |
| Surgical Candidate 4 Weeks | Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Adenoma-Part 1 | 431 pg/ml |
| Surgical Candidate 4 Weeks | Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN low-Part 2 | 594 pg/ml |
| Surgical Candidate 4 Weeks | Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN NOS-Part 4 | 417 pg/ml |
| Surgical Candidate 4 Weeks | Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Invasive-Part 3 | 453 pg/ml |
| Surgical Candidate 6 Months | Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN NOS-Part 4 | 88 pg/ml |
| Surgical Candidate 6 Months | Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Invasive-Part 3 | 184 pg/ml |
| Surgical Candidate 6 Months | Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN low-Part 2 | 366 pg/ml |
| Surgical Candidate 6 Months | Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months | IPMN Adenoma-Part 1 | 522 pg/ml |
Secondary
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.
Time frame: Baseline, 6 months, 1 year
Population: Data never collected for surgical arm; medical arm of study never initiated.