0822GCC: Phase 2 Study of Efficacy and Safety of Apricoxib/Placebo With Docetaxel or Pemetrexed in Non-Small Cell Lung Cancer

• Sponsor: University of Maryland, Baltimore (Other)
• Overall Status: Completed
• CT.gov ID: NCT00771953
• Collaborator: Tragara Pharmaceuticals, Inc. (Industry)
• Enrollment: 109
• Locations: 12
• Arms: 2
• Duration (Months): 73
• Patients Per Site: 9.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective is to determine the anti-tumor activity of the combination of apricoxib

• either docetaxel (AP/DC) or pemetrexed (AP/PE) compared with placebo + either docetaxel (P/DC) or pemetrexed (P/PE) as measured by progression free survival in patients with Stage IIIb (pleural effusion)or Stage IV non-small cell lung cancer (NSCLC).

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer; Non Small Cell Lung Cancer	Drug: apricoxib; Drug: Placebo; Drug: Docetaxel or Pemetrexed	Phase 2

Detailed Description

Patients diagnosed with advanced non-small cell lung cancer that has not responded to platinum-based chemotherapy are eligible to particvpate in this study.

Current standard treatments for this type of lung cancer are generally not effective in preventing the cancer from growing. The purpose of this study is to see if adding the drug apricoxib to standard chemotherapy is effective in treting NSCLC. Apricoxib is an investigational drug. Investigational means that it is not approved by the Food and Drug Administration (FDA). Laboratory studies suggest that apricoxib may be useful in the treatment of cancer . This is seen particularly when it is combined with chemotherapy drugs. However, this has not been proven in humans.

Laboratory evidence indicates that apricoxib may benefit patients whose disease over-produces a substance called COX-2. COX-2 can be detected in the urine as a substance called PGE-M (prostaglandin E metabolite). It is thought that patients who have a PGE-M level in the urine that decreases by at least half after taking apricoxib may benefit more than patients whose urine PGE-M decreases by less than half after apricoxib.

This study evaluated whether adding apricoxib to standard chemotherapy treatment will improve outcomes in patients with non-small cell lung cancer whose urine PGE-M decreases at least 50% after taking apricoxib. Apricoxib or placebo was added to either docetaxel or pemetrexed treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 109 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 0822GCC Randomized, Double-Blind, Placebo-Controlled Multicenter Phase 2 Study of the Efficacy and Safety of Apricoxib in Combination With Either Docetaxel or Pemetrexed in Non-Small Cell Lung Cancer Patients
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Apricoxib Apricoxib 400mg once a day	Drug: apricoxib; Oral apricoxib tablets will be provided as white or off-white film-coated tablets available in 100mg strength to be taken every day; Drug: Docetaxel or Pemetrexed; Docetaxel 75mg/m2 or Pemetrexed 500mg/m2 given as an IV infusion every 21 days. TheTreating physician will determine chemotherapy drug as per his usual practice.
Placebo Comparator: Placebo Placebo once a day	Drug: Placebo; Oral placebo tablets will be provided as white or off-white film-coated tablets to be taken every day; Drug: Docetaxel or Pemetrexed; Docetaxel 75mg/m2 or Pemetrexed 500mg/m2 given as an IV infusion every 21 days. TheTreating physician will determine chemotherapy drug as per his usual practice.

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival [From the date of randomization until the first date that recurrent or progressive disease is objectively documented.]

   For determining progression-free survival, progression was determined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). Progression was defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

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 non-small cell lung cancer (NSCLC), including stage IIIb (pleural effusion) (histology or cytology acceptable).

• Documented progression after 1 prior platinum-based chemotherapy. No more than one prior chemotherapy regimen is permitted. Patients may have also received erlotinib (before, after or concurrently with platinum based therapy).

• Measurable disease by RECIST criteria

• Age at least 18 years.

• ECOG performance status of 0-2.

• Required Laboratory Values (within 28 days before randomization) :

• Hb ≥ 9.0gm/dL; transfusions permitted

• ANC ≥ 1500/mm3

• Platelets ≥ 100,000/mm3

• INR ≤ 1.5

• Serum creatinine (Cr) within normal limits for laboratory OR Creatinine clearance greater than or equal to 45 ml/min. 24 hour measured CCr is also acceptable (calculated by the Cockcroft and Gault equation).

• SGOT and SGPT < 2 X the ULN; if liver metastases are present then must be < 5 X the ULN

• Bilirubin ≤ Institutional ULN

• Albumin ≥ or equal to 2.5 mg/dl

• May have been treated with anti-EGFR kinase therapy in addition to a platinum based therapy or concurrently with platinum therapy.

• Provide written informed consent and HIPAA authorization and agree to abide by the study restrictions and return for the required assessments.

• Women of child-bearing potential must have negative pregnancy test (serum B-HCG) with a sensitivity of at least 50 mIU/L within 7 days prior to the initiation of treatment and must have used effective contraception (recommended to be two reliable forms of contraception used simultaneously) or must have been sexually abstinent for at least 4 weeks prior to the negative pregnancy test through entry in the study.

• Female patients and male patients with female partners of child-bearing potential must agree to sexual abstinence or to practice effective contraception (recommended to be two reliable forms of contraception used simultaneously). At least one non-hormonal method strongly recommended. Male patients with female sexual partners who are pregnant, or of childbearing potential must agree to use condoms during and for at least 1 month after the last dose of apricoxib.

Exclusion Criteria:

• Pregnant or breast feeding

• Known hypersensitivity to apricoxib, docetaxel, other drugs formulated with polysorbate 80, pemetrexed, sulfonamides, aspirin, or other NSAIDs.

• Radiation therapy within 2 weeks or chemotherapy within 3 weeks or non-cytotoxic investigational agents within 3 weeks of initiating study treatment or patients who have not recovered from adverse effects due to agents administered > 3 weeks prior to initiating study treatment. Screening for urinary PGE-M suppression may begin during this time period.

• Evidence of New York Heart Association class III or greater cardiac disease. History of myocardial infarction, stroke, ventricular arrhythmia, or symptomatic conduction abnormality within 12 months.

• Concurrent severe or uncontrolled medical disease that could compromise the safety of the patient or compromise the ability of the patient to complete the study.

• Known HIV infection or AIDS. Testing not required.

• Symptomatic central nervous system metastases; the patient must be stable after radiotherapy for ≥ 2 weeks. Patients must be off all steroid or antiseizure medications for this indication for ≥ 2 weeks. Patients with CNS metastases that are untreated are eligible if there is no evidence of midline shift, requirement for steroids or antiseizure medications or neurologic symptoms.

• History of upper GI bleeding, ulceration, or perforation within the past 5 years.

• Concurrent use of COX-2 inhibitors or other NSAIDs for 2 days prior to the first dose of study treatment and during study, including aspirin for 7 days prior to the first dose of study treatment and during study.

• Previous COX-2 inhibitor therapy for this diagnosis.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
2	Mercy Research Institute	Miami	Florida	United States	33133
3	University of Miami	Miami	Florida	United States	33136
4	Rush University Medical Center	Chicago	Illinois	United States	60612
5	University of Maryland Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
6	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
7	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87106
8	Weill Medical Cornell University	New York	New York	United States	10065
9	Stony Brook Cancer Center (SUNY)	Stony Brook	New York	United States	11794
10	Providence Portland Medical Center	Portland	Oregon	United States	97213
11	Abramson Cancer Center of Uof Pennsylvania	Philadelphia	Pennsylvania	United States	19104
12	West Virginia University Clinical Trials Research Unit	Morgantown	West Virginia	United States	26506

Sponsors and Collaborators

• University of Maryland, Baltimore
• Tragara Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Martin J Edelman, University of Maryland Greenebaum Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• Edelman MJ, Watson D, Wang X, Morrison C, Kratzke RA, Jewell S, Hodgson L, Mauer AM, Gajra A, Masters GA, Bedor M, Vokes EE, Green MJ. Eicosanoid modulation in advanced lung cancer: cyclooxygenase-2 expression is a positive predictive factor for celecoxib + chemotherapy--Cancer and Leukemia Group B Trial 30203. J Clin Oncol. 2008 Feb 20;26(6):848-55. doi: 10.1200/JCO.2007.13.8081.
• Gitlitz BJ, et al. Apricot-l: Results of a biomarker-based phase II randomized placebocontrolled study of apricoxib in combination with erlotinib in non-small cell lung cancer (NSCLC) patients. Journal of Clinical Oncology 29: 2011 (suppl; abstr 7528)
• Groen HJ, Sietsma H, Vincent A, Hochstenbag MM, van Putten JW, van den Berg A, Dalesio O, Biesma B, Smit HJ, Termeer A, Hiltermann TJ, van den Borne BE, Schramel FM. Randomized, placebo-controlled phase III study of docetaxel plus carboplatin with celecoxib and cyclooxygenase-2 expression as a biomarker for patients with advanced non-small-cell lung cancer: the NVALT-4 study. J Clin Oncol. 2011 Nov 10;29(32):4320-6. doi: 10.1200/JCO.2011.35.5214. Epub 2011 Oct 11.
• Markowitz SD. Aspirin and colon cancer--targeting prevention? N Engl J Med. 2007 May 24;356(21):2195-8.
• Murphey LJ, Williams MK, Sanchez SC, Byrne LM, Csiki I, Oates JA, Johnson DH, Morrow JD. Quantification of the major urinary metabolite of PGE2 by a liquid chromatographic/mass spectrometric assay: determination of cyclooxygenase-specific PGE2 synthesis in healthy humans and those with lung cancer. Anal Biochem. 2004 Nov 15;334(2):266-75.
• Rao PN, Grover RK. Apricoxib, a COX-2 inhibitor for the potential treatment of pain and cancer. IDrugs. 2009 Nov;12(11):711-22.
• Reckamp KL, Krysan K, Morrow JD, Milne GL, Newman RA, Tucker C, Elashoff RM, Dubinett SM, Figlin RA. A phase I trial to determine the optimal biological dose of celecoxib when combined with erlotinib in advanced non-small cell lung cancer. Clin Cancer Res. 2006 Jun 1;12(11 Pt 1):3381-8.

• Responsible Party: University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT00771953
• Other Study ID Numbers: HP-00043076; 0822GCC; UMGCC 0822
• First Posted: Oct 15, 2008
• Last Update Posted: Oct 30, 2019
• Last Verified: Oct 1, 2019

• Keywords provided by University of Maryland, Baltimore: apricoxib; docetaxel; pemetrexed; Stage IIIb or Stage IV
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Docetaxel; Pemetrexed

Study Results

Participant Flow

Recruitment Details	University Medical Centers and Hospital Based Oncology Programs recruited participants from November 2011 through August 2011
Pre-assignment Detail	110 patients started a 5 day run in period with 400mg apricoxib. 7 did not complete due to AEs, and 23 did not have at least 50% drop in PGE-M (randomization requirement). Of the remaining 80, 2 withdrew, 2 were ineligible by physician discretion, 1 died and 3 had progressive disease. Thus, 72 patients were randomized.

Arm/Group Title	Apricoxib Plus Docetaxel or Pemetrexed	Placebo Plus Docetaxel or Pemetrexed
Arm/Group Description	Apricoxib 400mg qd and either docetaxel 75mg/m2 or pemetrexed 500mg/m2 q21 days	Placebo and either docetaxel 75mg/m2 or pemetrexed 500mg/m2 q21 days
Period Title: Overall Study
STARTED	36	36
COMPLETED	26	26
NOT COMPLETED	10	10

Baseline Characteristics

Arm/Group Title	Apricoxib Plus Docetaxel or Pemetrexed	Placebo Plus Docetaxel or Pemetrexed	Total
Arm/Group Description	Apricoxib 400mg qd and either docetaxel 75mg/m2 or pemetrexed 500mg/m2 q21 days	Placebo and either docetaxel 75mg/m2 or pemetrexed 500mg/m2 q21 days	Total of all reporting groups
Overall Participants	36	36	72
Age, Customized (years) [Median (Full Range) ]
Median (Full Range) [years]	62	66	64
Sex: Female, Male (Count of Participants)
Female	16 44.4%	16 44.4%	32 44.4%
Male	20 55.6%	20 55.6%	40 55.6%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival
Description	For determining progression-free survival, progression was determined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). Progression was defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	From the date of randomization until the first date that recurrent or progressive disease is objectively documented.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Apricoxib Plus Docetaxel	Placebo Plus Docetaxel	Apricoxib Plus Pemetrexed	Placebo Plus Pemetrexed
Arm/Group Description	Apricoxib 400mg qd plus docetaxel 75mg/m2 q21 days	Placebo plus docetaxel 75mg/m2 q21 days	Apricoxib 400mg qd plus pemetrexed 500mg/m2 q21 days	Placebo plus pemetrexed 500mg/m2 q21 days
Measure Participants	17	20	19	16
Median (95% Confidence Interval) [days]	75	97	103	98

Adverse Events

Arm/Group Title	Apricoxib Plus Docetaxel or Pemetrexed		Placebo Plus Docetaxel or Pemetrexed
Arm/Group Description	Apricoxib 400mg qd and either docetaxel 75mg/m2 or pemetrexed 500mg/m2 q21 days		Placebo and either docetaxel 75mg/m2 or pemetrexed 500mg/m2 q21 days
All Cause Mortality
	Apricoxib Plus Docetaxel or Pemetrexed		Placebo Plus Docetaxel or Pemetrexed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Apricoxib Plus Docetaxel or Pemetrexed		Placebo Plus Docetaxel or Pemetrexed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/36 (30.6%)		11/36 (30.6%)
Blood and lymphatic system disorders
Febrile neutropenia	0/36 (0%)	0	1/36 (2.8%)	1
Neutropenia	0/36 (0%)	0	2/36 (5.6%)	3
Granulocytopenia	1/36 (2.8%)	1	0/36 (0%)	0
Thrombosis	0/36 (0%)	0	2/36 (5.6%)	2
Cardiac disorders
Atrial flutter	1/36 (2.8%)	1	0/36 (0%)	0
Gastrointestinal disorders
Colonic perforation	1/36 (2.8%)	1	0/36 (0%)	0
General disorders
Abdominal pain	0/36 (0%)	0	2/36 (5.6%)	2
Chest pain	0/36 (0%)	0	1/36 (2.8%)	1
Coumadin toxicity	1/36 (2.8%)	1	0/36 (0%)	0
Dehydration	0/36 (0%)	0	1/36 (2.8%)	1
Headache	1/36 (2.8%)	1	1/36 (2.8%)	1
Hyperkalemia	1/36 (2.8%)	2	0/36 (0%)	0
Hypernatremia	0/36 (0%)	0	1/36 (2.8%)	1
Hyponatremia	0/36 (0%)	0	1/36 (2.8%)	1
Hypoxia	1/36 (2.8%)	1	1/36 (2.8%)	1
Hepatobiliary disorders
Creatinine increase	0/36 (0%)	0	1/36 (2.8%)	1
Hypoglycemia	1/36 (2.8%)	1	0/36 (0%)	0
Infections and infestations
Infection	1/36 (2.8%)	1	0/36 (0%)	0
Pneumonia	0/36 (0%)	0	1/36 (2.8%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Death	0/36 (0%)	0	1/36 (2.8%)	1
Nervous system disorders
Aseptic meningitis	1/36 (2.8%)	1	0/36 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchitis	1/36 (2.8%)	1	0/36 (0%)	0
CPOD exacerbation	1/36 (2.8%)	1	0/36 (0%)	0
Cough	0/36 (0%)	0	1/36 (2.8%)	1
Dyspnea	2/36 (5.6%)	2	0/36 (0%)	0
Pulmonary embolism	1/36 (2.8%)	1	0/36 (0%)	0
Other (Not Including Serious) Adverse Events
	Apricoxib Plus Docetaxel or Pemetrexed		Placebo Plus Docetaxel or Pemetrexed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/36 (33.3%)		11/36 (30.6%)
Blood and lymphatic system disorders
Leukopenia	3/36 (8.3%)	3	0/36 (0%)	0
Lymphopenia	1/36 (2.8%)	1	3/36 (8.3%)	3
Neutropenia	9/36 (25%)	9	9/36 (25%)	10
Lowered WBC count	2/36 (5.6%)	3	1/36 (2.8%)	1
General disorders
Hyponatremia	2/36 (5.6%)	3	0/36 (0%)	0

Limitations/Caveats

This study is limited by the relatively low numbers and the hetereogeneity between concurrent treatments (docetaxel vs. pemetrexed). However, in analyses stratified by docetaxel and pemetrexed, results for an affect of apricoxib were still null.

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.