Randomized Double-blinded Comparative Trial to Study the Add-on Activity of Combination Treatment of Nicotinamide on Progression Free Survival for EGFR Mutated Lung Cancer Terminal Stage Patients Being Treated With Gefitinib or Erlotinib
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Hazard ratio (PFS) of the nicotinamide arm to the placebo arm
研究概览
简要总结
Nicotinamide is an inhibitor of human sirtuins (HDAC III), and is found to re-activate epigenetically silenced tumor suppressors, RUNX3 (runt-related gene 3) and others, in cancer cells. Nicotinamide was found to be effective in several animal cancer models including lung, bladder, liver, etc. The purpose of this study is to determine whether nicotinamide is also effective in the treatment of human lung cancer.
详细描述
The standard therapy to the EGFR (epidermal growth factor receptor) mutation positive non-small-cell lung cancer patients who are not eligible to operation is to administer EGFR-TKIs (tyrosine kinase inhibitors, gefitinib or erlotinib). To determine the effectiveness of nicotinamide on lung cancer, nicotinamide or placebo tablet will be co-administered with gefitinib or erlotinib for two years until the event or censoring occurs. The stratified block randomization was designed with 3 covariates (EGFR mutation status, kind of EGFR-TKI, ECOG (Eastern Cooperative Oncology Group) performance status score variation). The size of lesions will be checked every other months by radiology. PD (progressive disease) will be assessed according to RECIST(Response Evaluation Criteria in Solid Tumors)1.1. After observing 36 events, an interim analysis of hazard ratio by Cox proportional hazard regression will be performed. The final analysis will be done by the same protocol after observation of 72 events. The significance level of the interim and final analysis were set to 0.0075 and 0.0209 respectively. Response rate, quality of life (measured by 10 questions at every visit), and overall survival will be analysed together. All other adverse reactions will be analysed and reported, if there.
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
- Triple (Participant, Care Provider, 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
- •Operation-impossible stage 4 non-small-cell lung carcinoma (NSCLC), or recurred terminal stage NSCLC after previous operation or radiation therapy
- •EGFR mutated (exon 19 deletion or L858R mutation)
- •Life expectation more than 3 months
- •More than 1 measurable lesions by RECIST 1.1 which were not exposed to radiation previously
- •ECOG (Eastern Cooperative Oncology Group ) performance status grade 0~2
- •Who signed the informed consent form
排除标准
- •Who had received chemotherapy or EGFR tyrosin kinase inhibitors previously, except whom had received operation at least 6 months ago and received supplementary chemotherapy
- •Who has metastasized brain lesion that needs operation or radiation therapy
- •Above grade 2, CTCAE (Common Toxicity Criteria for Adverse Effects) 4.0 criteria for blood, liver and kidney
- •Who does Not agree to contraception
- •Who has allergy to nicotinamide
研究组 & 干预措施
Nicotinamide
Nicotinamide with EGFR-TKI:
- gefitinib (250mg tab) or erlotinib (150mg tab) - per oral, once a day
- nicotinamide (500mg tab) - per oral, twice a day, until the event or censoring occurs
干预措施: Nicotinamide (Drug)
Placebo
Placebo tablet with EGFR-TKI:
- gefitinib (250mg tab) or erlotinib (150mg tab) - per oral, once a day
- placebo tablet - per oral, twice a day, until the event or censoring occurs
干预措施: Nicotinamide (Drug)
结局指标
主要结局
Hazard ratio (PFS) of the nicotinamide arm to the placebo arm
时间窗: two year
Cox regression analysis
次要结局
- Response rate(two year)
- Difference in quality of life between the nicotinamide arm and the placebo arm(two year)
- Overall survival(two year)
研究者
Il Yeong Park, Ph.D.
Professor
Chungbuk National University