Adjuvant Celecoxib in Completely Resected pN1-2 NSCLC Patients
The aim of the study is to assess the influence of celecoxib on relapse-free survival in completely resected patients with poor prognosis indicated by metastatic involvement of intrapulmonary/hilar (pN1) or ipsilateral mediastinal (pN2) lymph nodes. Celecoxib, a selective oral COX-2 inhibitor, was found to exert significant anti-proliferative activity against a variety of tumor cell lines in vitro, including NSCLC. COX-2 is frequently up-regulated in NSCLC cell lines and archival tumor samples. Its high expression was also correlated with poor prognosis of the patients. A clinical trial addressing the role of celecoxib as adjuvant treatment in radically operated patients with high risk of relapse is warranted.
1. Rationale and objectives
To assess the influence of celecoxib on relapse-free survival in completely resected patients with poor prognosis indicated by metastatic involvement of intrapulmonary/hilar (pN1) or ipsilateral mediastinal (pN2) lymph nodes. Celecoxib, a selective oral COX-2 inhibitor, was found to exert significant anti-proliferative activity against a variety of tumor cell lines in vitro, including NSCLC. COX-2 is frequently up-regulated in NSCLC cell lines and archival tumor samples. Its high expression was also correlated with poor prognosis of the patients. Proposed mechanisms of action of selective COX-2 inhibitors include inhibition of angiogenesis, inhibition of matrix metalloproteinase-2 expression and induction of apoptosis. A clinical trial addressing the role of celecoxib as adjuvant treatment in radically operated patients with high risk of relapse is warranted.
2. Study design
A multicenter, international, randomized, double-blind, placebo controlled phase III clinical trial
3. Primary endpoint
The primary endpoint will be relapse-free survival (time to local or distant relapse) during the study.
4. Other endpoints
Secondary end-points will include:
- overall survival (time to death of any cause)
- the safety of the long-term administration of celecoxib
5. Statistical methods
The primary objective, i.e. relapse-free survival (RFS), will be recorded as time from randomization to date of local or distant relapse (date of radiological imaging demonstrating relapse or date of histological confirmation of relapse or date of relapse on clinical examination, if above data are not available) or death of any cause, whichever occurs first. Patients alive without relapse at the end of their follow-up will be considered censored observations.
The study aims at the verification of the null hypothesis Ho : RFS in the control group = RFS in the treated group vs. the alternative HA : RFS in the control group ≠RFS in the treated group Primary and secondary efficacy analyses will be performed using intention-to-treat principle.
The distribution of RFS and OS in the compared treatment arms will be summarized graphically using the Kaplan-Meier method and compared by the log-rank test. The result of the test will be assessed using the 5% significance level (two-sided).
The effect of the treatment on the distribution of RFS and OS will be evaluated by the score test based on the Cox proportional hazards model, which will include stratification and other relevant clinical factors as covariates.
The proportion of patients experiencing any AE, any serious AE, and specific types of AEs and proportion of withdrawals will be compared between the treatment arms using the chi-square test at the 5% significance level (two-sided).
6. Translational research A research project evaluating immunohistochemical expression of COX-2, VEGF and CD34 as a marker of vascular density will be performed. These parameters will be analyzed in a central laboratory by two independent pathologists involved in angiogenesis research. Immunohistochemical methods will be carefully validated before commencement of translational research part of the study.
The study centers will be requested to provide post-operative tissue samples (paraffin-embedded blocks or 5 unstained slides) from the primary tumor.
Trt.groups Drug Form Route Dose interval Dosing No. of patients
1. Celecoxib tablets p.o. 400 mg 12 h 271
2. Placebo tablets p.o. 400 mg 12 h 271
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Non-Small Cell Lung Cancer
Medical University of Gdansk
Medical University of Gdansk
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT00211952
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Malignant neoplasm arising from the epithelium of the BRONCHI. It represents a large group of epithelial lung malignancies which can be divided into two clinical groups: SMALL CELL LUNG CANCER and NON-SMALL-CELL LUNG CARCINOMA.
Small Cell Lung Carcinoma
A form of highly malignant lung cancer that is composed of small ovoid cells (SMALL CELL CARCINOMA).
Carcinoma, Non-small-cell Lung
A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.
Tumor Suppressor Protein P53
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
Tumors or cancer of the LUNG.
The purpose of this study is to investigate the effect of the adminstration of celecoxib, a cox2-inhibitor in patients with stage II-III non small cell lung cancer receiving radical radio...
The primary purpose of the study is to investigate if daily treatment with celecoxib, an inhibitor of cyclooxygenase-2, can prolong survival in patients with advanced non-small cell lung c...
RATIONALE: Celecoxib may slow the growth of cancer by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing...
RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Celecoxib may slow the growth of cancer by stopping blood flow to the tumor...
This phase II trial is studying how well giving erlotinib together with celecoxib works in treating patients with recurrent stage IIIB or stage IV non-small cell lung cancer. Erlotinib and...
Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor with antitumor and antiangiogenic activities. To investigate the effects of celecoxib on nasopharyngeal carcinoma (NPC), HNE-1 cells were tr...
BACKGROUND: Tumor suppressor in lung cancer-1 (TSLC1) belongs to immunoglobulin superfamily of cell adhesion molecule and differentially expressed in adenocarcinoma of the lung (4.1B)belongs to NF2/ER...
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.
PURPOSE Cyclooxygenase-2 (COX-2) protein expression in patients with non-small-cell lung cancer (NSCLC) may be not only a prognostic marker but also predictive for COX-2 inhibition. We hypothesized th...
BRAF mutations have been found to be a driver mutation and maybe a therapy target in patients with non-small cell lung cancer. This article reviews the current understanding of BRAF gene, its structur...
Cisplatin is a chemotherapeutic drug widely used for the treatment of gastric cancer. The benefit of including COX-2-selective inhibitors in cisplatin-based regimens on anti-cancer effect remains unce...