APRiCOT-P: Study of Apricoxib With Gemcitabine and Erlotinib to Treat Advanced Pancreatic Cancer

• Sponsor: Tragara Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00709826
• Collaborator: (none)
• Enrollment: 109
• Locations: 39
• Arms: 2
• Duration (Months): 33
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will compare the anti-tumor efficacy of apricoxib and gemcitabine/erlotinib with placebo and gemcitabine/erlotinib in patients with advanced pancreatic cancer.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer; Metastatic Pancreatic Cancer	Drug: gemcitabine; Drug: placebo; Drug: Erlotinib; Drug: apricoxib	Phase 2

Detailed Description

This study will compare the anti-tumor efficacy of apricoxib and gemcitabine/erlotinib with placebo and gemcitabine/erlotinib as measured by progression-free survival to test the hypothesis that down regulation of COX-2 and EGFR pathways in patients with up-regulated COX-2 expression in tumors will have a clinical benefit compared with Gemcitabine/Erlotinib only.

Study Design

• Study Type: Interventional
• Actual Enrollment: 109 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: APRiCOT-P (Apricoxib in Combination Oncology Treatment - Pancreas): Phase 2 Study of the Efficacy and Safety of Apricoxib in Combination With Gemcitabine and Erlotinib in the Treatment of Patients With Advanced Pancreatic Cancer
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: apricoxib + gemcitabine + erlotinib 400mg apricoxib + 1000mg/m2 gemcitabine + 100mg erlotinib	Drug: gemcitabine; Gemcitabine: per package insert.; Other Names: Gemcitabine - Gemzar ; Drug: Erlotinib; Erlotinib - per package insert.; Other Names: Erlotinib - Tarceva ; Drug: apricoxib; apricoxib: 100mg tablets, given orally; Other Names: No other names
Placebo Comparator: placebo + gemcitabine + erlotinib placebo + 1000mg/m2 gemcitabine + 100mg erlotinib	Drug: gemcitabine; Gemcitabine: per package insert.; Other Names: Gemcitabine - Gemzar ; Drug: placebo; placebo: 100 mg tablets, 400 mg/day; Other Names: No other names ; Drug: Erlotinib; Erlotinib - per package insert.; Other Names: Erlotinib - Tarceva

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival [Randomization then every other cycle]

   Progression is defined, using RECIST, as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline.

Secondary Outcome Measures

1. Overall Survival [Randomization then every other cycle]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Histologically or cytologically confirmed adenocarcinoma of the pancreas that is locally advanced or metastatic.

2. Life expectancy greater than or equal to 3 months.

3. Patients must have measurable disease by RECIST.

4. ECOG PS of 0, 1, or 2.

5. Negative serum pregnancy test at the time of first dose for women of childbearing potential.

Exclusion Criteria:

1. Previous chemotherapy as primary treatment for locally advanced or metastatic pancreatic cancer(stage 3 T3 and T4, and all stage 4).

2. RT within 2 weeks or chemotherapy within 3 weeks or noncytotoxic investigational agents within 4 weeks of initiating study treatment.

3. Evidence of New York Heart Association class III or greater cardiac disease.

4. History of myocardial infarction, stroke, ventricular arrhythmia.

5. Symptomatic central nervous system metastases.

6. Pregnant or nursing women.

7. Hypersensitivity or intolerance to apricoxib, erlotinib, gemcitabine, sulfonamides, aspirin, or other non-steroidal anti-inflammatory drugs (NSAIDs).

8. History of upper gastrointestinal bleeding, ulceration or perforation. History of lower GI bleeding, ulceration, or perforation within 12 months.

9. Previous anti-EGFR kinase therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Clinical Research Center	Tucson	Arizona	United States	85715
2	Comprehensive Blood and Cancer Center	Bakersfield	California	United States	93309
3	Southbay Oncology Hematology Partners	Campbell	California	United States	95008
4	Bay Area Cancer Research Group, LLC	Concord	California	United States	94523
5	Bay Area Cancer Research Group, LLC	Pleasant Hill	California	United States	94523
6	North America Research Institute	San Dimas	California	United States	91773
7	Front Range Cancer Specialists	Ft. Collins	Colorado	United States	80528
8	Oncology Associates of Bridgeport	Trumball	Connecticut	United States	06611
9	Hematology Oncology Associates	Lake Worth	Florida	United States	33461
10	Hematology Oncology Associates of Treasure Coast	Port St. Lucie	Florida	United States	34952
11	The Queen's Medical Center Cancer Center	Honolulu	Hawaii	United States	96813
12	Rush-Copley Medical Center	Aurora	Illinois	United States	60504
13	Alexian Brothers Medical Hospital Network	Elk Grove Village	Illinois	United States	60007
14	Investigative Clinical Research of Indiana, LLC	Indianapolis	Indiana	United States	46260
15	Medical Consultants, PC	Muncie	Indiana	United States	47303
16	University of Iowa Hospitals	Iowa City	Iowa	United States	52242
17	Owsley Brown Frazier Cancer Center	Louisville	Kentucky	United States	40245
18	Jayne Gurtler, MD	Metairie	Louisiana	United States	70006
19	Franklin Square Hospital Center/Harry and Jeanette Weinberg Cancer Institute at Franklin Square	Baltimore	Maryland	United States	21237
20	SJMH Cancer Center	Ann Arbor	Michigan	United States	48106
21	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
22	Warren Hospital	Phillipsburg	New Jersey	United States	08865
23	San Juan Oncology Associates	Farmington	New Mexico	United States	87401
24	Bronx River Medical Associates, P.C.	Bronx	New York	United States	10467
25	Cancer Care of WNC, PA	Asheville	North Carolina	United States	28801
26	Southeastern Medical Oncology Center	Goldsboro	North Carolina	United States	27534
27	Southeastern Medical Oncology Center	Wilson	North Carolina	United States	27893
28	Samaritan Hematology * Oncology	Corvallis	Oregon	United States	97330
29	Eastern Regional Medical Center	Philadelphia	Pennsylvania	United States	19124
30	Associates in Hematology-Oncology PC	Upland	Pennsylvania	United States	19013
31	Berks Hematology-Oncology Associates, Ltd	West Reading	Pennsylvania	United States	19612
32	Charleston Hematology Oncology Associates	Charleston	South Carolina	United States	29414
33	JTV Cancer Care Institute	Rapid City	South Dakota	United States	57701
34	The Jones Clinic	Germantown	Tennessee	United States	38138
35	Tennessee Cancer Specialists	Knoxville	Tennessee	United States	37920
36	Coastal Bend Cancer Center	Corpus Christi	Texas	United States	78463
37	The Center for Cancer and Blood Disorders	Fort Worth	Texas	United States	76104
38	The Methodist Hospital	Houston	Texas	United States	77030
39	Cascade Cancer Center	Kirkland	Washington	United States	98304

Sponsors and Collaborators

• Tragara Pharmaceuticals, Inc.

Investigators

• Study Director: Tracy Parrott, Tragara Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tragara Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT00709826
• Other Study ID Numbers: TP2001-203; APRiCOT-P
• First Posted: Jul 3, 2008
• Last Update Posted: Nov 7, 2012
• Last Verified: Oct 1, 2012

• Additional relevant MeSH terms: Pancreatic Neoplasms; Gemcitabine; Erlotinib Hydrochloride

Study Results

Participant Flow

Recruitment Details	Study opened to accrual in August 2008. Enrollment closed on November 2010. One hundred and nine patients were randomized. Patients were recruited from clinical oncology practices.

Arm/Group Title	Apricoxib/Gemcitabine/Erlotinib	Placebo/Gemcitabine/Erlotinib
Arm/Group Description	Patients randomized to receive apricoxib + gemcitabine + erlotinib.	Patients randomized to receive placebo + gemcitabine + erlotinib.
Period Title: Overall Study
STARTED	70	39
COMPLETED	68	38
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Apricoxib/Gemcitabine/Erlotinib	Placebo/Gemcitabine/Erlotinib	Total
Arm/Group Description	Patients randomized to receive apricoxib + gemcitabine + erlotinib.	Patients randomized to receive placebo + gemcitabine + erlotinib.	Total of all reporting groups
Overall Participants	70	39	109
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	38 54.3%	17 43.6%	55 50.5%
>=65 years	32 45.7%	22 56.4%	54 49.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63 (64.2)	67 (66)	64 (64.8)
Sex: Female, Male (Count of Participants)
Female	41 58.6%	22 56.4%	63 57.8%
Male	29 41.4%	17 43.6%	46 42.2%
Region of Enrollment (participants) [Number]
United States	70 100%	39 100%	109 100%

Outcome Measures

1. Secondary Outcome

Title	Overall Survival
Time Frame	Randomization then every other cycle

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Apricoxib/Gemcitabine/Erlotinib	Placebo/Gemcitabine/Erlotinib
Arm/Group Description	Patients randomized to receive apricoxib + gemcitabine + erlotinib.	Patients randomized to receive placebo + gemcitabine + erlotinib.
Measure Participants	70	39
Median (95% Confidence Interval) [Months]	5.0	4.8

2. Primary Outcome

Title	Progression Free Survival
Description	Progression is defined, using RECIST, as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline.
Time Frame	Randomization then every other cycle

Outcome Measure Data

Analysis Population Description

A 1-sided log rank test was used to achieve 80% power at an α=0.20 significance level to detect a difference of 0.16 between the proportions of patients who were progression free in AP/EG (0.35) and P/EG (0.19) after 9 months; an overall sample size of approximately 110 patients (73 in AP/EG and 37 in P/EG) was randomized in a 2:1 ratio.

Arm/Group Title	Apricoxib/Gemcitabine/Erlotinib	Placebo/Gemcitabine/Erlotinib
Arm/Group Description	Patients randomized to receive apricoxib + gemcitabine + erlotinib.	Patients randomized to receive placebo + gemcitabine + erlotinib.
Measure Participants	70	39
Median (95% Confidence Interval) [Months]	3.0	2.8

Adverse Events

Time Frame	First dose of study drug to 30 days after last dose of study drug
Adverse Event Reporting Description	Only drug-related serious adverse events are listed.
Arm/Group Title	Apricoxib/Gemcitabine/Erlotinib		Placebo/Gemcitabine/Erlotinib
Arm/Group Description	Patients randomized to receive apricoxib + gemcitabine + erlotinib.		Patients randomized to receive placebo + gemcitabine + erlotinib.
All Cause Mortality
	Apricoxib/Gemcitabine/Erlotinib		Placebo/Gemcitabine/Erlotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Apricoxib/Gemcitabine/Erlotinib		Placebo/Gemcitabine/Erlotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/70 (22.9%)		5/39 (12.8%)
Blood and lymphatic system disorders
Anemia	1/70 (1.4%)	1	0/39 (0%)	0
Cardiac disorders
Myocardial infarction	0/70 (0%)	0	1/39 (2.6%)	1
Gastrointestinal disorders
Duodenal ulcer perforation	1/70 (1.4%)	1	0/39 (0%)	0
Gastrointestinal hemorrhage	5/70 (7.1%)	5	0/39 (0%)	0
Nausea	1/70 (1.4%)	1	0/39 (0%)	0
Esophagitis ulcerative	1/70 (1.4%)	1	0/39 (0%)	0
Ulcer	1/70 (1.4%)	1	0/39 (0%)	0
Vomiting	1/70 (1.4%)	1	1/39 (2.6%)	1
Infections and infestations
Pneumocystis jiroveci pneumonia	1/70 (1.4%)	1	0/39 (0%)	0
Sepsis	1/70 (1.4%)	1	0/39 (0%)	0
Investigations
International normalized ratio increased	1/70 (1.4%)	1	0/39 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/70 (1.4%)	1	0/39 (0%)	0
Failure to thrive	0/70 (0%)	0	1/39 (2.6%)	1
Nervous system disorders
Headache	0/70 (0%)	0	1/39 (2.6%)	1
Renal and urinary disorders
Renal failure	1/70 (1.4%)	1	0/39 (0%)	0
Renal failure acute	1/70 (1.4%)	1	0/39 (0%)	0
Vascular disorders
Cerebrovascular accident	1/70 (1.4%)	1	0/39 (0%)	0
Embolic stroke	0/70 (0%)	0	1/39 (2.6%)	1
Pulmonary embolism	1/70 (1.4%)	1	0/39 (0%)	0
Other (Not Including Serious) Adverse Events
	Apricoxib/Gemcitabine/Erlotinib		Placebo/Gemcitabine/Erlotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	70/70 (100%)		39/39 (100%)
Blood and lymphatic system disorders
Anemia	37/70 (52.9%)	37	18/39 (46.2%)	18
Thrombocytopenia	29/70 (41.4%)	29	14/39 (35.9%)	14
Neutropenia	21/70 (30%)	21	13/39 (33.3%)	13
Gastrointestinal disorders
Diarrhea	41/70 (58.6%)	41	17/39 (43.6%)	17
Nausea	41/70 (58.6%)	41	15/39 (38.5%)	15
Constipation	26/70 (37.1%)	26	7/39 (17.9%)	7
Vomiting	23/70 (32.9%)	23	12/39 (30.8%)	12
Abdominal pain	21/70 (30%)	21	6/39 (15.4%)	6
Mucosal inflammation	12/70 (17.1%)	12	4/39 (10.3%)	4
Abdominal distension	10/70 (14.3%)	10	3/39 (7.7%)	3
Dyspepsia	9/70 (12.9%)	9	1/39 (2.6%)	1
Gastrointestinal hemorrhage	8/70 (11.4%)	8	1/39 (2.6%)	1
Abdominal pain upper	7/70 (10%)	7	3/39 (7.7%)	3
Ascites	6/70 (8.6%)	6	1/39 (2.6%)	1
Flatulence	6/70 (8.6%)	6	0/39 (0%)	0
Stomatitis	5/70 (7.1%)	5	1/39 (2.6%)	1
Gastroesophageal reflux disease	4/70 (5.7%)	4	2/39 (5.1%)	2
General disorders
Fatigue	40/70 (57.1%)	40	24/39 (61.5%)	24
Dehydration	17/70 (24.3%)	17	6/39 (15.4%)	6
Asthenia	9/70 (12.9%)	9	6/39 (15.4%)	6
Chills	8/70 (11.4%)	8	4/39 (10.3%)	4
Pyrexia	5/70 (7.1%)	5	7/39 (17.9%)	7
Edema	4/70 (5.7%)	4	2/39 (5.1%)	2
Pain	4/70 (5.7%)	4	3/39 (7.7%)	3
Hepatobiliary disorders
Jaundice	6/70 (8.6%)	6	3/39 (7.7%)	3
Hyperbilirubinemia	4/70 (5.7%)	4	3/39 (7.7%)	3
Infections and infestations
Pneumonia	6/70 (8.6%)	6	2/39 (5.1%)	2
Cellulitis	5/70 (7.1%)	5	1/39 (2.6%)	1
Upper respiratory tract infection	5/70 (7.1%)	5	1/39 (2.6%)	1
Urinary tract infection	4/70 (5.7%)	4	7/39 (17.9%)	7
Investigations
Weight decreased	6/70 (8.6%)	6	4/39 (10.3%)	4
Alanine aminotransferase increased	5/70 (7.1%)	5	2/39 (5.1%)	2
Liver function test abnormal	5/70 (7.1%)	5	1/39 (2.6%)	1
Aspartate aminotransferase increased	4/70 (5.7%)	4	2/39 (5.1%)	2
Metabolism and nutrition disorders
Anorexia	18/70 (25.7%)	18	6/39 (15.4%)	6
Hypokalemia	10/70 (14.3%)	10	6/39 (15.4%)	6
Decreased appetite	4/70 (5.7%)	4	5/39 (12.8%)	5
Hypomagnesemia	2/70 (2.9%)	2	6/39 (15.4%)	6
Hyponatremia	2/70 (2.9%)	2	6/39 (15.4%)	6
Musculoskeletal and connective tissue disorders
Edema peripheral	21/70 (30%)	21	18/39 (46.2%)	18
Back pain	7/70 (10%)	7	3/39 (7.7%)	3
Nervous system disorders
Dizziness	10/70 (14.3%)	10	5/39 (12.8%)	5
Dysgeusia	5/70 (7.1%)	5	4/39 (10.3%)	4
Headache	5/70 (7.1%)	5	2/39 (5.1%)	2
Psychiatric disorders
Insomnia	11/70 (15.7%)	11	5/39 (12.8%)	5
Anxiety	7/70 (10%)	7	3/39 (7.7%)	3
Depression	5/70 (7.1%)	5	5/39 (12.8%)	5
Renal and urinary disorders
Renal failure	6/70 (8.6%)	6	0/39 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	22/70 (31.4%)	22	14/39 (35.9%)	14
Cough	8/70 (11.4%)	8	5/39 (12.8%)	5
Skin and subcutaneous tissue disorders
Rash	32/70 (45.7%)	32	20/39 (51.3%)	20
Dermatitis Acneiform	15/70 (21.4%)	15	2/39 (5.1%)	2
Night sweats	7/70 (10%)	7	1/39 (2.6%)	1
Alopecia	5/70 (7.1%)	5	4/39 (10.3%)	4
Dry skin	5/70 (7.1%)	5	2/39 (5.1%)	2
Pruritus	5/70 (7.1%)	5	6/39 (15.4%)	6
Erythema	4/70 (5.7%)	4	2/39 (5.1%)	2
Vascular disorders
Deep vein thrombosis	8/70 (11.4%)	8	5/39 (12.8%)	5
Epistaxis	7/70 (10%)	7	4/39 (10.3%)	4
Hypotension	7/70 (10%)	7	5/39 (12.8%)	5
Pulmonary embolism	4/70 (5.7%)	4	4/39 (10.3%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.