TP2001-201: APRiCOT-L: Study to Evaluate Efficacy and Safety of Apricoxib With Erlotinib in Patients With Non-small Cell Lung Cancer

• Sponsor: Tragara Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00652340
• Collaborator: (none)
• Enrollment: 120
• Locations: 47
• Arms: 2
• Duration (Months): 47
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will compare the anti-tumor efficacy of apricoxib and erlotinib with placebo and erlotinib as measured by time to disease progression to test the hypothesis that down regulation of COX-2 and EGFR pathways in patients with up-regulated COX-2 expression in tumor will have a clinical benefit compared with erlotinib alone.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Non Small Cell Lung Cancer	Drug: apricoxib/erlotinib; Drug: erlotinib/placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: APRiCOT-L (Apricoxib in Combination Oncology Treatment - Lung) A Randomized, Double-Blind, Placebo-Controlled Multicenter Phase 2 Study of the Efficacy and Safety of Apricoxib in Combination With Erlotinib in Non-Small Cell Lung Cancer Patients
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A	Drug: apricoxib/erlotinib; apricoxib: 100 mg tablets, 400mg/day erlotinib: per package insert
Placebo Comparator: B	Drug: erlotinib/placebo; erlotinib: per package insert placebo: 100 mg tablets, 400 mg/day

Outcome Measures

Primary Outcome Measures

1. Time to Disease Progression (TDP) [Baseline and every other cycle.]

Secondary Outcome Measures

1. Overall Survival [Randomization and every cycle]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Pathologically determined Stage IV NSCLC including Stage IIIb (pleural effusion)

• Failed at least one prior platinum-based chemotherapy for Stage IIIb or Stage IV NSCLC. Patients receiving platinum-based chemotherapy only given in an adjuvant setting are not eligible.

• Measurable disease by RECIST

• Greater than or equal to 18 years of age

• ECOG PS of 0 or 1

Exclusion Criteria:

• Radiation therapy within 2 weeks; chemotherapy within 3 weeks; non-cytotoxic investigational agents within 4 weeks of initiating study treatment

• Evidence of NYHA class III or greater cardiac disease

• History of MI, stroke, ventricular arrhythmia, or symptomatic conduction abnormality within 12 months

• Known HIV infection or AIDS

• Symptomatic CNS metastases

• Pregnant or nursing women

• Hypersensitivity or intolerance to erlotinib, sulfonamides, aspirin, or other NSAIDs.

• History of upper GI bleeding, ulceration, or perforation

• Prior history of COX-2 inhibitor therapy for the treatment of metastatic NSCLC

• Previous anti-EGFR kinase therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Tucson	Arizona	United States
2		Bakersfield	California	United States
3		Los Angeles	California	United States
4		Rancho Mirage	California	United States
5		San Diego	California	United States
6		San Dimas	California	United States
7		Stockton	California	United States
8		Norwich	Connecticut	United States
9		Lake North	Florida	United States
10		Lakeland	Florida	United States
11		Miami	Florida	United States
12		Savannah	Georgia	United States
13		Chicago	Illinois	United States
14		Kokomo	Indiana	United States
15		New Albany	Indiana	United States
16		Waterloo	Iowa	United States
17		Louisville	Kentucky	United States
18		New Orleans	Louisiana	United States
19		Ann Arbor	Michigan	United States
20		Jackson	Michigan	United States
21		Lansing	Michigan	United States
22		Livonia	Michigan	United States
23		Saginaw	Michigan	United States
24		St. Joseph	Michigan	United States
25		Robbinsdale	Minnesota	United States
26		St. Louis	Missouri	United States
27		Neptune	New Jersey	United States
28		Elmhurst	New York	United States
29		Stony Brook	New York	United States
30		Gastonia	North Carolina	United States
31		Wilmington	North Carolina	United States
32		Akron	Ohio	United States
33		Canton	Ohio	United States
34		Columbus	Ohio	United States
35		Jefferson City	Ohio	United States
36		Sylvania	Ohio	United States
37		Corvallis	Oregon	United States
38		Portland	Oregon	United States
39		Upland	Pennsylvania	United States
40		Charleston	South Carolina	United States
41		Arlington	Texas	United States
42		Galveston	Texas	United States
43		Newport News	Virginia	United States
44		Richmond	Virginia	United States
45		Tacoma	Washington	United States
46		Huntington	West Virginia	United States
47		Morgantown	West Virginia	United States

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: NCT00652340
• Other Study ID Numbers: TP2001-201; APRiCOT-L
• First Posted: Apr 3, 2008
• Last Update Posted: Apr 9, 2012
• Last Verified: Mar 1, 2012

• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Erlotinib Hydrochloride

Study Results

Participant Flow

Recruitment Details	The study opened to accural in April 2008. Enrollment closed in May 2010. One hundred seventy six patients were enrolled with 120 patients randomized. Patients were recruited from clinical oncology practices.
Pre-assignment Detail	Enrolled patients underwent a 5-day open label treatment with apricoxib to determine the maximum suppression of PGEM from a baseline measurment. PGEM was used as a biomarker of COX-2 activity in the tumor. Patients with at least a 50% decrease on day 5 from their baseline measurment were eligible to be randomized.

Arm/Group Title	Apricoxib/Erlotinib	Placebo/Erlotinib
Arm/Group Description	Patients randomized to receive apricoxib and erlotinib.	Patients randomized to receive placebo and erlotinib.
Period Title: Overall Study
STARTED	78	42
COMPLETED	74	39
NOT COMPLETED	4	3

Baseline Characteristics

Arm/Group Title	Apricoxib/Erlotinib	Placebo/Erlotinib	Total
Arm/Group Description	Patients randomized to receive apricoxib and erlotinib.	Patients randomized to receive placebo and erlotinib.	Total of all reporting groups
Overall Participants	78	42	120
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	46 59%	23 54.8%	69 57.5%
>=65 years	32 41%	19 45.2%	51 42.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.1 (10.78)	64.6 (11.16)	62.9 (10.94)
Sex: Female, Male (Count of Participants)
Female	36 46.2%	17 40.5%	53 44.2%
Male	42 53.8%	25 59.5%	67 55.8%
Region of Enrollment (participants) [Number]
United States	78 100%	42 100%	120 100%

Outcome Measures

1. Primary Outcome

Title	Time to Disease Progression (TDP)
Time Frame	Baseline and 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 0.13 between the proportions of patients who are progression free in AP/E (0.34) and P/E (0.21) after 5 months; an overall sample size of 115 patients (77 in AP/E and 38 in P/E) will be randomized in a 2:1 ratio in this study.

Arm/Group Title	Apricoxib/Erlotinib	Placebo/Erlotinib
Arm/Group Description	Patients randomized to receive apricoxib and erlotinib.	Patients randomized to receive placebo and erlotinib.
Measure Participants	78	42
Median (95% Confidence Interval) [months]	1.80	2.10

2. Secondary Outcome

Title	Overall Survival
Time Frame	Randomization and every cycle

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Apricoxib/Erlotinib	Placebo/Erlotinib
Arm/Group Description	Patients randomized to receive apricoxib and erlotinib.	Patients randomized to receive placebo and erlotinib.
Measure Participants	78	42
Median (95% Confidence Interval) [months]	5.90	5.60

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/Erlotinib		Placebo/Erlotinib
Arm/Group Description	Patients randomized to receive apricoxib and erlotinib.		Patients randomized to receive placebo and erlotinib.
All Cause Mortality
	Apricoxib/Erlotinib		Placebo/Erlotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Apricoxib/Erlotinib		Placebo/Erlotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/78 (16.7%)		4/42 (9.5%)
Blood and lymphatic system disorders
Anemia	1/78 (1.3%)	1	0/42 (0%)	0
Thrombocytopenia	0/78 (0%)	0	1/42 (2.4%)	1
Cardiac disorders
Acute myocardial infarction	1/78 (1.3%)	1	0/42 (0%)	0
Left ventricular dysfunction	1/78 (1.3%)	1	0/42 (0%)	0
Myocardial infarction	0/78 (0%)	0	1/42 (2.4%)	1
Gastrointestinal disorders
Diarrhea	2/78 (2.6%)	2	0/42 (0%)	0
Gastric ulcer perforation	1/78 (1.3%)	1	0/42 (0%)	0
Gastrointestinal hemorrhage	1/78 (1.3%)	1	1/42 (2.4%)	1
Intestinal perforation	1/78 (1.3%)	1	0/42 (0%)	0
Peritonitis	1/78 (1.3%)	1	0/42 (0%)	0
Investigations
Blood creatinine increased	1/78 (1.3%)	1	0/42 (0%)	0
Nervous system disorders
Cerebral infarction	1/78 (1.3%)	1	0/42 (0%)	0
Cerebrovascular accident	1/78 (1.3%)	1	0/42 (0%)	0
Renal and urinary disorders
Renal failure acute	1/78 (1.3%)	1	0/42 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumonia	0/78 (0%)	0	1/42 (2.4%)	1
Hemoptysis	0/78 (0%)	0	1/42 (2.4%)	1
Pulmonary fibrosis	1/78 (1.3%)	1	0/42 (0%)	0
Other (Not Including Serious) Adverse Events
	Apricoxib/Erlotinib		Placebo/Erlotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	77/78 (98.7%)		42/42 (100%)
Blood and lymphatic system disorders
Anemia	9/78 (11.5%)	9	2/42 (4.8%)	2
Cardiac disorders
Hypertension	5/78 (6.4%)	5	2/42 (4.8%)	2
Gastrointestinal disorders
Diarrhea	41/78 (52.6%)	41	25/42 (59.5%)	25
Nausea	27/78 (34.6%)	27	12/42 (28.6%)	12
Vomiting	16/78 (20.5%)	16	4/42 (9.5%)	4
Mucosal inflammation	15/78 (19.2%)	15	4/42 (9.5%)	4
Constipation	12/78 (15.4%)	12	5/42 (11.9%)	5
Dyspepsia	10/78 (12.8%)	10	6/42 (14.3%)	6
Abdominal pain	5/78 (6.4%)	5	5/42 (11.9%)	5
Dysgeusia	5/78 (6.4%)	5	3/42 (7.1%)	3
General disorders
fatigue	33/78 (42.3%)	33	12/42 (28.6%)	12
Anorexia	17/78 (21.8%)	17	15/42 (35.7%)	15
Weight decreased	9/78 (11.5%)	9	6/42 (14.3%)	6
Dehydration	7/78 (9%)	7	3/42 (7.1%)	3
Infections and infestations
Pneumonia	7/78 (9%)	7	4/42 (9.5%)	4
Investigations
Blood creatinine increased	9/78 (11.5%)	9	0/42 (0%)	0
Musculoskeletal and connective tissue disorders
Edema peripheral	8/78 (10.3%)	8	6/42 (14.3%)	6
Back pain	7/78 (9%)	7	5/42 (11.9%)	5
Nervous system disorders
Dizziness	10/78 (12.8%)	10	4/42 (9.5%)	4
Psychiatric disorders
Insomnia	11/78 (14.1%)	11	7/42 (16.7%)	7
Anxiety	7/78 (9%)	7	1/42 (2.4%)	1
Depression	6/78 (7.7%)	6	2/42 (4.8%)	2
Respiratory, thoracic and mediastinal disorders
Cough	18/78 (23.1%)	18	5/42 (11.9%)	5
Dyspnea	16/78 (20.5%)	16	11/42 (26.2%)	11
Wheezing	6/78 (7.7%)	6	1/42 (2.4%)	1
Hemoptysis	5/78 (6.4%)	5	2/42 (4.8%)	2
Skin and subcutaneous tissue disorders
Rash	42/78 (53.8%)	42	23/42 (54.8%)	23
Dry skin	20/78 (25.6%)	20	11/42 (26.2%)	11
Dermatitis acneiform	13/78 (16.7%)	13	11/42 (26.2%)	11
Pruritis	10/78 (12.8%)	10	9/42 (21.4%)	9
Epistaxis	7/78 (9%)	7	1/42 (2.4%)	1
Alopecia	6/78 (7.7%)	6	4/42 (9.5%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.