A Randomized Phase III Double Blind Trial Evaluating Selective COX-2 Inhibition in COX-2 Expressing Advanced Non-Small Cell Lung Cancer
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 313
- 试验地点
- 398
- 主要终点
- Progression-free Survival
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pemetrexed disodium and celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving gemcitabine hydrochloride or pemetrexed disodium together with carboplatin is more effective with or without celecoxib in treating non-small cell lung cancer.
PURPOSE: This randomized phase III trial is studying gemcitabine hydrochloride, pemetrexed disodium, and carboplatin to compare how well they work when given together with celecoxib or a placebo in treating patients with advanced non-small cell lung cancer.
详细描述
OBJECTIVES:
Primary
- To confirm the beneficial effect of gemcitabine hydrochloride or pemetrexed disodium in combination with carboplatin with or without celecoxib in patients with advanced non-small cell lung cancer that expresses COX-2.
Secondary
- To describe the response rate in patients treated with these regimens.
- To describe the distribution of progression-free survival (PFS) and overall survival of patients treated with these regimens.
- To compare the PFS of patients with COX-2 index ≥ 2 (adjusting for CYP2C9 genotype and celecoxib trough concentrations as covariates) treated with these regimens.
- To correlate urinary PGE-M level with COX-2 expression, COX-2 inhibition, and outcome.
- To evaluate the association between the -765G/C polymorphism in PTGS2 and COX-2 expression in non-small cell lung cancer specimens.
- To characterize a trough plasma celecoxib concentration which will be used as a measure of patient adherence to study treatment and which may be used in future studies for correlations with genotype and pharmacodynamic outcomes.
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 (Participant, Investigator)
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive gemcitabine hydrochloride* IV on days 1 and 8 OR pemetrexed disodium* IV on day 1. Patients also receive carboplatin IV on day 1 and oral celecoxib twice daily on days 1-21.
干预措施: carboplatin (Drug)
Arm I
Patients receive gemcitabine hydrochloride* IV on days 1 and 8 OR pemetrexed disodium* IV on day 1. Patients also receive carboplatin IV on day 1 and oral celecoxib twice daily on days 1-21.
干预措施: celecoxib (Drug)
Arm I
Patients receive gemcitabine hydrochloride* IV on days 1 and 8 OR pemetrexed disodium* IV on day 1. Patients also receive carboplatin IV on day 1 and oral celecoxib twice daily on days 1-21.
干预措施: gemcitabine hydrochloride (Drug)
Arm I
Patients receive gemcitabine hydrochloride* IV on days 1 and 8 OR pemetrexed disodium* IV on day 1. Patients also receive carboplatin IV on day 1 and oral celecoxib twice daily on days 1-21.
干预措施: pemetrexed disodium (Drug)
Arm II
Patients receive gemcitabine hydrochloride* OR pemetrexed disodium* and carboplatin as in arm I. Patients also receive oral placebo twice daily on days 1-21.
干预措施: carboplatin (Drug)
Arm II
Patients receive gemcitabine hydrochloride* OR pemetrexed disodium* and carboplatin as in arm I. Patients also receive oral placebo twice daily on days 1-21.
干预措施: gemcitabine hydrochloride (Drug)
Arm II
Patients receive gemcitabine hydrochloride* OR pemetrexed disodium* and carboplatin as in arm I. Patients also receive oral placebo twice daily on days 1-21.
干预措施: pemetrexed disodium (Drug)
Arm II
Patients receive gemcitabine hydrochloride* OR pemetrexed disodium* and carboplatin as in arm I. Patients also receive oral placebo twice daily on days 1-21.
干预措施: placebo (Other)
结局指标
主要结局
Progression-free Survival
时间窗: Time between randomization and disease relapse or death from any cause, assessed up to 5 years
Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
次要结局
- Overall Survival(Time between randomization and death from any cause, assessed up to 5 years)
- Response Rate(Up to 5 years)
- Incidence of Toxicities as Assessed by NCI CTCAE v. 4.0(Up to 5 years)
- Prognostic Value of Urinary Prostaglandin Metabolites (PGE-M) Levels for Worse PFS for Patients Who Had Baseline Urinary PGE-M Above/Below the First Quartile (Q1)(Up to 5 years)
- Prognostic Value of Urinary Prostaglandin Metabolites (PGE-M) Levels for Worse PFS for Patients Who Had Baseline Urinary PGE-M Above/Below the Median Quartile (Q2)(Up to 5 years)
- Prognostic Value of Urinary Prostaglandin Metabolites (PGE-M) Levels for Worse PFS for Patients Who Had Baseline Urinary PGE-M Above/Below the Third Quartile (Q3)(Up to 5 years)