A Retrospective Study of Clinical Outcomes and Liver-related Toxicity of Patients With Lung Cancer Treated With Immune-checkpoint Inhibitors
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 500
- 试验地点
- 3
- 主要终点
- Number of participants with immune-mediated hepatitis
研究概览
简要总结
Immune-checkpoint inhibitors have recently become available as a new therapy for a variety of cancers. This drugs function by boosting the anti-cancer immune response, but unfortunately, may cause off-target, non-specific immune activation, resulting in liver and gut toxicity. In order to understand the development of liver immune-related adverse events we aim to collect full clinicopathological data from patients with advanced lung cancer treated with immune-checkpoint inhibitors at Blacktown, Westmead and Nepean Hospitals. Patients treated with standard chemotherapy will be used as a control group.
This study aims to establish clinical risk factors that can predict the occurrence of liver immune-related adverse events in patients with advanced lung cancer treated with immune-checkpoint inhibitors. Such predictors may assist in the stratification of patients based on their risk for development liver toxicity as a result of immunotherapy, allowing early cessation/modification of treatment prior to the development of severe adverse reactions. In addition, this retrospective study will aim to determine the significance of pre-existing liver damage on the development of liver adverse events as well as establish a timeline defining the development of adverse events in the liver.
详细描述
BACKGROUND AND RATIONALE.
Lung cancer is the most common cause of cancer-related mortality worldwide. This year alone 12,817 new lung cancer cases were registered in Australia, the mortality rate of which being 46% within 5 years. Chemotherapy is still considered the first-line treatment, however recent clinical trials have established that with treatment monoclonal antibodies known as immune-checkpoint inhibitors shows higher efficacy in terms of overall survival and progression-free survival. Despite higher efficacy, immune-checkpoint inhibitors can cause a number of immune-related adverse events which may force patients to cease treatment. Among these side effects, liver toxicity occurs rapidly and is asymptomatic in the early stages. These facts underscore the necessity of stratifying patients based on their risk of developing liver toxicity. We aim to predict liver toxicity early on in therapy using data collected from routine clinical testing.
STUDY AIMS / OBJECTIVES.
This retrospective study aims to answer following research questions:
- Does pre-existing liver fibrosis/cirrhosis influence the development of liver immune-related adverse events?
- What is the first time-point and subsequent timeline of liver immune-related adverse events occurrence and progression?
- What clinical markers predict immunotherapy related toxicity?
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Advanced lung cancer (stage IV)
- •Treatment - immune-checkpoint inhibitors or chemotherapy
- •Data is fully available for the whole period of observation
排除标准
- •Radiologically reported liver metastases
- •Concurrent treatment with both therapeutic regimes
结局指标
主要结局
Number of participants with immune-mediated hepatitis
时间窗: Week 6-12 from treatment commencement
Baseline risk factors significantly correlated with hepatic immune-related adverse events
时间窗: Week 0
Blood test results, BMI, FibroScan data will be correlated with the development of liver toxicity
次要结局
- Number of participants with non-hepatic immune-related adverse events(Week 3-32 from treatment commencement)
- Baseline risk factors significantly correlated with non-hepatic immune-related adverse events(Week 0)
研究者
Golo Ahlenstiel
Professor of Medicine
Western Sydney Local Health District