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

• Sponsor: Indiana University School of Medicine (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00198081
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Arms: 2
• Duration (Months): 79
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pancreas Neoplasms	Drug: COX-2 Inhibitor 6-8 weeks prior to surgery; Drug: COX-2 Inhibitor for 6 months prior to follow-up EUS or ERCP	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase II Trial of Celecoxib in Patients With IPMN
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Surgical Candidate COX-2 Inhibitor 6-8 weeks prior to surgery	Drug: COX-2 Inhibitor 6-8 weeks prior to surgery; 400 mg BID 6-8 weeks prior to surgery; Other Names: Celecoxib
Experimental: Medical Candidate 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; 400 mg BID for 6 months prior to follow-up EUS or ERCP; Other Names: Celecoxib

Outcome Measures

Primary Outcome Measures

1. 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

2. 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

3. 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

4. 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

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University Hospital	Indianapolis	Indiana	United States	46202

Sponsors and Collaborators

• Indiana University School of Medicine

Investigators

• Principal Investigator: Christian M. Schmidt, MD, Indiana University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Indiana University School of Medicine
• ClinicalTrials.gov Identifier: NCT00198081
• Other Study ID Numbers: 0305-20
• First Posted: Sep 20, 2005
• Last Update Posted: Feb 29, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by Indiana University School of Medicine: celecoxib for pancreas lesions
• Additional relevant MeSH terms: Neoplasms; Pancreatic Neoplasms; Celecoxib; Cyclooxygenase 2 Inhibitors

Study Results

Participant Flow

Arm/Group Title	Surgical Candidate	Medical Candidate
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	5	0
COMPLETED	4	0
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Surgical Candidate	Medical Candidate	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	5	0	5
Age (participants) [Number]
<=18 years	0 0%	0 NaN
Between 18 and 65 years	2 40%	2 Infinity
>=65 years	3 60%	3 Infinity
Gender (participants) [Number]
Female	0 0%	0 NaN
Male	5 100%	5 Infinity
Ethnicity (NIH/OMB) (participants) [Number]
Hispanic or Latino	0 0%	0 NaN
Not Hispanic or Latino	5 100%	5 Infinity
Unknown or Not Reported	0 0%	0 NaN
Race (NIH/OMB) (participants) [Number]
American Indian or Alaska Native	0 0%	0 NaN
Asian	0 0%	0 NaN
Native Hawaiian or Other Pacific Islander	1 20%	1 Infinity
Black or African American	0 0%	0 NaN
White	4 80%	4 Infinity
More than one race	0 0%	0 NaN
Unknown or Not Reported	0 0%	0 NaN
Region of Enrollment (participants) [Number]
United States	5 100%	5 Infinity
IPMN type (participants) [Number]
Adenoma	1 20%	1 Infinity
Low grade	1 20%	1 Infinity
Invasive	1 20%	1 Infinity
Not Otherwise Specified	1 20%	1 Infinity
Unknown	1 20%	1 Infinity

Outcome Measures

1. Primary Outcome

Title	Concentration of PGE2 in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Surgical Candidate Baseline	Surgery Candidate Surgery	Surgical Candidate One Week	Surgical Candidate 4 Weeks	Surgical Candidate 6 Months
Arm/Group Description	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	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	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	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	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
Measure Participants	4	4	4	4	4
IPMN Adenoma-Part 1	11800	13300	12100	19600	24000
IPMN low-Part 2	21000	13400	4700	36300	16000
IPMN Invasive-Part 3	800	30000	15400	24800	3600
IPMN NOS-Part 4	10100	8700	9500	40300	7500

2. Secondary Outcome

Title	Number of Participants With Clinical Changes in IPMN Progression.
Description	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

Outcome Measure Data

Analysis Population Description

Data never collected for surgical arm; medical arm of study never initiated.

Arm/Group Title	Surgical Candidate	Medical Candidate
Arm/Group Description	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	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
Measure Participants	0	0

3. Primary Outcome

Title	Concentration of PGE2 in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Surgical Candidate Baseline	Surgery Candidate Surgery	Surgical Candidate One Week	Surgical Candidate 4 Weeks	Surgical Candidate 6 Months
Arm/Group Description	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	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	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	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	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
Measure Participants	4	4	4	4	4
IPMN Adenoma-Part 1	60	70	70	130	100
IPMN low-Part 2	170	90	10	40	10
IPMN Invasive-Part 3	70	30	60	10	70
IPMN NOS-Part 4	100	140	20	80	30

4. Primary Outcome

Title	Concentration of PGEM in Urine at Baseline, Surgery, 1 wk, 4wks, and 6 Months
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Surgical Candidate Baseline	Surgery Candidate Surgery	Surgical Candidate One Week	Surgical Candidate 4 Weeks	Surgical Candidate 6 Months
Arm/Group Description	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	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	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	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	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
Measure Participants	4	4	4	4	4
IPMN Adenoma-Part 1	196	177	354	431	522
IPMN low-Part 2	257	201	153	594	366
IPMN Invasive-Part 3	128	NA	850	453	184
IPMN NOS-Part 4	131	100	184	417	88

5. Primary Outcome

Title	Concentration of PGEM in Serum at Baseline, Surgery, 1 wk, 4wks, and 6 Months
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Surgical Candidate Baseline	Surgery Candidate Surgery	Surgical Candidate One Week	Surgical Candidate 4 Weeks	Surgical Candidate 6 Months
Arm/Group Description	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	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	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	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	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
Measure Participants	4	4	4	4	4
IPMN Adenoma-Part 1	20	4	6.4	5.4	6.7
IPMN low-Part 2	7	4.3	9.3	5.9	8.7
IPMN Invasive-Part 3	2	3	11.8	5.1	8.3
IPMN NOS-Part 4	9	3.4	7.2	4.3	1.8

Adverse Events

Time Frame	6 months
Arm/Group Title	Surgical Candidate		Medical Candidate
Arm/Group Description	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		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
All Cause Mortality
	Surgical Candidate		Medical Candidate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Surgical Candidate		Medical Candidate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40%)		0/0 (NaN)
Cardiac disorders
CARDIAC DISORDERS - OTHER, [CONGESTIVE HEART FAILURE]	1/5 (20%)	1	0/0 (NaN)	1
Nervous system disorders
NERVOUS SYSTEM DISORDERS - OTHER, [NEUROLEPTIC REACTION]	1/5 (20%)	1	0/0 (NaN)	1
Other (Not Including Serious) Adverse Events
	Surgical Candidate		Medical Candidate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		0/0 (NaN)
Cardiac disorders
EKG CHANGES	1/5 (20%)	1	0/0 (NaN)	1
PALPITATIONS	1/5 (20%)	1	0/0 (NaN)	1
ARRTHYTHMIA	1/5 (20%)	1	0/0 (NaN)	1
ATRIAL FIBRILLATION	1/5 (20%)	1	0/0 (NaN)	1
Gastrointestinal disorders
DIARRHEA	2/5 (40%)	2	0/0 (NaN)	2
PANCREATIC FISTULA	1/5 (20%)	1	0/0 (NaN)	1
PAIN	1/5 (20%)	1	0/0 (NaN)	1
General disorders
FATIGUE	2/5 (40%)	2	0/0 (NaN)	2
EDEMA: LIMB SWELLING OF THE ARMS AND/OR LEGS	1/5 (20%)	1	0/0 (NaN)	1
FLU-TYPE SYMPTOMS (INCLUDING BODY ACHES, FEVER, CHILLS, TIREDNESS,LOSS OF APPETITE, COUGH)	1/5 (20%)	1	0/0 (NaN)	1
Infections and infestations
TOOTH INFECTION	1/5 (20%)	1	0/0 (NaN)	1
Injury, poisoning and procedural complications
SEROMA	1/5 (20%)	1	0/0 (NaN)	1
Investigations
INR INCREASED	1/5 (20%)	1	0/0 (NaN)	1
PLATELET COUNT DECREASED	1/5 (20%)	1	0/0 (NaN)	1
Musculoskeletal and connective tissue disorders
ARTHRALGIA	1/5 (20%)	1	0/0 (NaN)	1
Respiratory, thoracic and mediastinal disorders
COUGH	2/5 (40%)	2	0/0 (NaN)	2
SORE THROAT	1/5 (20%)	1	0/0 (NaN)	1
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - OTHER, [RUNNY NOSE]	1/5 (20%)	1	0/0 (NaN)	1
Vascular disorders
HYPOTENSION	1/5 (20%)	1	0/0 (NaN)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.