Ignite Creation Date:
2024-05-05 @ 12:02 PM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00211952
Status:
SUSPENDED
Last Update Posted:
2005-09-21
First Post:
2005-09-13
Brief Title:
Adjuvant Celecoxib in Completely Resected pN1-2 NSCLC Patients
Sponsor:
Medical University of Gdansk
Organization:
Medical University of Gdansk
Study Overview
Official Title:
A Randomized Double Blind Placebo Controlled Phase III Trial Evaluating the Role of Adjuvant Celecoxib in Completely Resected High-Risk pN1-2 Non-Small Cell Lung Cancer NSCLC Patients
Status:
SUSPENDED
Status Verified Date:
2005-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 intrapulmonaryhilar 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
Detailed Description:
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 intrapulmonaryhilar 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 ie 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
7 Medication
Trtgroups Drug Form Route Dose interval Dosing No of patients
1 Celecoxib tablets po 400 mg 12 h 271
2 Placebo tablets po 400 mg 12 h 271
To assess the influence of celecoxib on relapse-free survival in completely resected patients with poor prognosis indicated by metastatic involvement of intrapulmonaryhilar 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 ie 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
7 Medication
Trtgroups Drug Form Route Dose interval Dosing No of patients
1 Celecoxib tablets po 400 mg 12 h 271
2 Placebo tablets po 400 mg 12 h 271
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None