Evaluation of Apricoxib (Selective Cyclooxygenase 2 Inhibition) in Modulating T Regulatory Cells of Patients With Early Stage Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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The primary objective for this trial is to determine the biological ability of apricoxib to decrease T reg cells in the peripheral blood and tumor infiltrating lymphocytes in subjects compared to those who have not in subjects with early stage Non-small Cell Lung Cancer (NSCLC). The secondary objectives are to determine the efficacy of apricoxib to inhibit CD4+CD25+ T reg and FOXP3 function and exploration of COX-2 dependent biomarkers of apoptosis resistance, angiogenesis, invasion, and immunity.

Official Title
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Evaluation of Apricoxib (Selective Cyclooxygenase 2 Inhibition) in Modulating T Regulatory Cells of Patients With Early Stage Non-small Cell Lung Cancer

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Apricoxib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults over the age of 18 capable of giving informed consent. Radiographic findings suspicious for primary lung cancer or pathologically confirmed NSCLC which is surgically resectable and radiographically early stage (stage I and II). ECOG performance status of 0, 1, or 2 (see Appendix A). Ineligible for or refuse preoperative chemotherapy or chemoradiation therapy Normal renal function (defined as serum creatinine ≤ 2 mg/dl or creatinine clearance ≥ 60 ml/min/1.73m2). Normal liver function (defined as total bilirubin ≤ 1.5 x ULN, SGOT & SGPT ≤ 2.5 xULN). Negative pregnancy test prior to initiation of treatment and adequate contraception throughout treatment. Preoperative pulmonary function test (PFT) with FEV1 and D LCO ≥ 60% or predicted postoperative FEV1 and DLCO ≥ 40% based on quantitative lung perfusion scan Must be able to come off anticoagulants and have normal coagulation studies (PTT < 40 seconds and INR < 1.4) prior to planned surgery. For subjects on COX-2 inhibitors or other NSAIDS prior to study initiation, cessation of the drug for 1 week prior to Apricoxib administration is required for study enrollment. Exclusion Criteria: Radiation therapy, chemotherapy, non-cytotoxic investigational agents, or corticosteroids within 4 weeks of initiating treatment. Comorbid disease or a medical condition that would impair the ability of the subject to receive or comply with the study protocol. Hypersensitivity to apricoxib, sulfonamides, aspirin, or other NSAIDS or to any reagents used in the study. Previous history of gastrointestinal ulceration, bleeding, or perforation. Required concurrent use of COX-2 inhibitors or other NSAIDS during Apricoxib administration. Chronic or concurrent use of steroids (topical steroids are acceptable if medically indicated). Pregnant or nursing women. Evidence of NYHA class III or greater cardiac disease. History of myocardial infarction, stroke, ventricular arrhythmia, or symptomatic conduction abnormality within 12 months of initiating treatment. History of heart surgery for coronary artery disease. Known HIV infection or AIDS.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apricoxib<br>As part of the trial, forty eligible subjects will be randomly assigned to receive Apricoxib 400 mg orally once daily or no drug intervention for a 7 day period (Days 0-6) prior to surgical resection of the lung tumor but between the two surgeries. | Drug: Apricoxib<br>* As part of the trial, forty eligible subjects will be randomly assigned to receive Apricoxib 400 mg orally once daily or no drug intervention for a 7 day period (Days 0-6) prior to surgical resection of the lung tumor but between the two surgeries.<br>|
| Other: No drug intervention<br> | Drug: Apricoxib<br>* As part of the trial, forty eligible subjects will be randomly assigned to receive Apricoxib 400 mg orally once daily or no drug intervention for a 7 day period (Days 0-6) prior to surgical resection of the lung tumor but between the two surgeries.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare Level of CD4+CD25high T Lymphocyte Regulatory Cells in Peripheral Blood Lymphocytes and Tumor Infiltrating Lymphocytes From Surgical Resection Specimens of Subjects With Early Stage NSCLC Who Have Received Apricoxib to Those Who Have Not | As part of the trial, forty eligible subjects will be randomly assigned to receive Apricoxib 400 mg orally once daily or no drug intervention for a 7 day period (Days 0-6) prior to surgical resection of the lung tumor but between the two surgeries. Peripheral blood and urine will be obtained on Days 0 and 7 from both groups (prior to surgical incision). Bronchoalveolar lavage (BAL) and lymph node tissue will be obtained on Days 0 and 7. TIL will be obtained from surgical resection specimens of the primary lung tumor only on Day 7 | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Apricoxib on Levels of CD4+CD25+ T Regulatory Cells in Peripheral Blood.Also,Biomarkers of Apoptosis Resistance,Angiogenesis,Invasion and Immunity Will be Tested in the Lab to Check How Effective Apricoxib is in Inhibiting These Proteins. | Peripheral blood from patients with NSCLC has been reported to have an increase in the percentages of CD4+CD25+ T reg cells.In contrast <10% of the PBLs of normal donors have this phenotype. As such, CD4+CD25+ cells will be assessed in addition to FOXP3 levels in PBL. In addition, exploration of COX-2 dependent biomarkers of apoptosis resistance, angiogenesis, invasion, and immunity will be studied. COX-2, FOXP3, IL-10, IL-12, MDC, CXCR4 and survivin will be analyzed in plasma. | 7 days |