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
试验速览
- 阶段
- 3 期
- 状态
- 暂停
- 入组人数
- 542
- 试验地点
- 1
- 主要终点
- time to progression
研究概览
简要总结
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.
详细描述
- 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
- Statistical methods
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- 未提供
结局指标
主要结局
time to progression
次要结局
- overall survival
- toxicity