A Randomized Phase II Study of Irinotecan/Cisplatin With or Without Simvastatin in Chemo-naive Patients With Extensive Disease-small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 入组人数
- 192
- 试验地点
- 1
- 主要终点
- 1-year survival rate
研究概览
简要总结
The purpose of this study is to compare the efficacy of Simvastatin and Irinotecan/Cisplatin chemotherapy with Irinotecan/Cisplatin chemotherapy alone in Extensive disease-small cell lung cancer.
详细描述
Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have been used to treat hypercholesterolemia. Besides the lipid lowering effects, they also act as anti-inflammatory and anti-cancer agents. Recently the investigators demonstrated a synergistic cytotoxicity between Simvastatin and Irinotecan in human lung cancer cells. Simvastatin enhances Irinotecan-induced apoptosis by inhibition of proteasome activity. All of these additional actions may counteract harmful effects of smoking-induced chronic inflammation. These properties together with a high safety profile have made Statins more attractive drug for small cell lung cancer (SCLC), the highly smoking-related cancer.
Given the promising preclinical anti-tumor and anti-inflammatory effects of Simvastatin in SCLC, recently the investigators conducted a phase II study of Simvastatin and Irinotecan/Cisplatin (IP) chemotherapy in chemo-naïve- patients with Extensive disease-small cell lung cancer (ED-SCLC). The 1-year survival rate was 39.3%. The median overall survival (OS) and progression free survival (PFS) was 11.0 months and 6.1 months, respectively. Overall relative risk (RR) was 75%. The most common toxicity was neutropenia (67%). The efficacy was significantly associated with smoking-status. Compared with never-smokers, ever-smokers had higher RR (40% v 78%, P=0.01) and longer PFS (2.5 months v 6.4 months, P=0.018) and showed a trend toward improved OS (9.0 months v 11.2 months, P=0.095). The effect of smoking on survival was apparent when subdividing ever smokers according to pack-years (PY). Ever-smokers who smoked > 65 PY showed significantly longer OS compared to ever-smokers who smoked <= 65 PY or never-smokers (20.6 months v 10.6 months v 9.0 months, log-rank P=0.032). In multivariate analysis, PY > 65 was predictive for longer survival (hazard ratio) HR=0.377 [95% CI (confidence interval), 0.157-0.905]). These findings suggest that the addition of Simvastatin to Irinotecan and Cisplatin improved efficacy in ever-smokers with ED-SCLC. The survival benefit of this combination seems apparent in heavy-smokers.
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
- None
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
- •Histologically confirmed SCLC
- •Extensive - stage disease, defined as disease extending beyond one hemithorax or involving contralateral mediastinal, hilar or supraclavicular lymph nodes, and/ or pleural effusion
- •ever smoker( have smoked> 100 cigarettes in entire lifetime
- •No prior chemotherapy, immunotherapy, or radiotherapy
- •Measurable disease according to RECIST 1.1
- •Patient compliance that allow adequate follow - up
- •Adequate hematologic , hepatic and renal function.
- •Written informed consent that is consistent with International Conference on Harmonization (ICH) - Good Clinical Practice (GCP) guidelines
- •Males of females at least 18 years of age
- •If female : childbearing potential either terminated by surgery, radiation, or menopause or attenuated by use of an approved contraceptive method(intrauterine device, birth control pills, or barrier device)during for 3 months after trial. If male, use of an approved contraceptive method during the study and 3 months afterwards. Females with childbearing potential must have a urine negative hCG test within 7 days prior to the study enrollment.
- •No concomitant prescriptions including cyclosporin A, valproic acid, phenobarbital, phenytoin, ketoconazole.
- •Patients with brain metastasis are allowed unless there were clinically significant neurological symptoms or signs.
排除标准
- •Inability to comply with protocol or study procedures.
- •A serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study.
- •A serious cardiac condition, such as myocardial infarction with 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV.
- •Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
- •Concurrent administration of any other antitumor therapy.
- •Pregnant or Breast-feeding.
- •Taking simvastatin or Any contraindications for therapy with simvastatin
研究组 & 干预措施
Control arm
IP chemotherapy arm
干预措施: IP chemotherapy (Drug)
Treatment arm
IP chemotherapy plus simvastatin arm
干预措施: IP chemotherapy plus simvastatin (Drug)
结局指标
主要结局
1-year survival rate
时间窗: every 8 weeks
Survival time will be calculated from the date of study treatment start to the date of death.( or date last seen ) Follow - up visits are conducted every 8 weeks to obtain meaningful data on time- to event variables. Assessment will continue until death or 12 months after treatment.
次要结局
- Tumor Response rate(every 2 cycles or 6 weeks)
- Progression free survival(every 2 cycles or 6 weeks.)
- Toxicity profile(every 3 weeks)
研究者
Ji-youn Han
Head, lung cancer center
National Cancer Center, Korea