Adjuvant Celecoxib in Completely Resected pN1-2 NSCLC Patients

NCT ID: NCT00211952

Last Updated: 2005-09-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Clinical Phase

PHASE3

Total Enrollment

542 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-03-31

Brief Summary

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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.

Detailed Description

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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.
7. Medication

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

Conditions

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Non-Small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Interventions

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celecoxib

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Eligibility criteria:

* Completely resected (R0), histologically confirmed NSCLC with pathological T1-T3 category and pathological proof of N1 or N2 disease
* Adequate pre-surgical disease assessment (chest CT and upper abdominal CT - mandatory; mediastinoscopy or PET mandatory if clinical N2 is suspected on chest CT; other examinations according to signs and symptoms to exclude metastatic disease)
* Adequate lymph node sampling
* Randomization between 14 and 42 days after surgery
* Adequate post-surgical recovery
* Age \> 18 years
* WHO Performance Status 0 or 1
* Adequate liver and renal function (ALT \< 1.5 ULN, bilirubin within normal limits, creatinine \< 1.5 ULN) and adequate haematology (haemoglobin \>11g/dL, WBC\>2.000/L, PLT\>100.000/L)
* Written informed consent
* No previous treatment with chemotherapy
* No histological diagnosis of SCLC or mixed NSCLC/SCLC type
* No apparent involvement of mediastinal lymph nodes at preoperative staging (cN2)
* No evidence of metastatic disease (M1)
* Stable medical conditions (e.g. no myocardial infarction within 12 months, unstable angina, active psychiatric disorder)
* No active infection
* No history of malignancy other than basal-cell skin cancer or in situ cervical cancer
* No history of severe renal or liver insufficiency
* No history of a recent gastrointestinal bleeding or active ulcer disease or extensive gastro-intestinal surgery that may affect the drug absorption
* No participation in any investigational study within 30 days prior to enrollment
* No pregnancy or lactation or inadequate contraception
* No known hypersensitivity to celecoxib, other COX-2 inhibitors or aspirin (aspirin triad)
* No chronic use of NSAID's (selective inhibitors of COX-2 and non- selective COX inhibitors), acetylsalicylic acid (aspirin) nor oral steroids \>14 days during one month prior to surgery nor anticipated chronic use of the above drugs during the study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Central and Eastern European Oncology Group

OTHER

Sponsor Role collaborator

Stowarzyszenie Ludzi Wyleczonych z Raka Płuca

UNKNOWN

Sponsor Role collaborator

Pharmacia

INDUSTRY

Sponsor Role collaborator

Medical University of Gdansk

OTHER

Sponsor Role lead

Principal Investigators

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Jacek Jassem, Professor

Role: PRINCIPAL_INVESTIGATOR

Medical University of Gdansk

Locations

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Medical University of Gdansk

Gdansk, , Poland

Site Status

Countries

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Poland

Other Identifiers

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0102 PLCSG

Identifier Type: -

Identifier Source: org_study_id