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

This study has been terminated.
(Drug sponsor stopped drug manufacture due to toxicity issues from other studies)
Sponsor:
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01532362
First received: November 30, 2011
Last updated: June 26, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention
Non Small Cell Lung Cancer
Drug: Apricoxib

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Evaluation of Apricoxib (Selective Cyclooxygenase 2 Inhibition) in Modulating T Regulatory Cells of Patients With Early Stage Non-small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Jonsson Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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 [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • 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. [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    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.


Enrollment: 1
Study Start Date: November 2011
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Apricoxib
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
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.
No drug intervention Drug: Apricoxib
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01532362

Locations
United States, California
Jonsson Comprehensive Cancer Center
Los Angeles, California, United States, 90095
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Investigators
Principal Investigator: Jay M Lee, M.D. University of California, Los Angeles
  More Information

No publications provided

Responsible Party: Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01532362     History of Changes
Other Study ID Numbers: 11-002081
Study First Received: November 30, 2011
Last Updated: June 26, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on July 24, 2014