Montreal Database and Biorepository of Cancer Patients Treated With Immune Checkpoint Inhibitors for the Study of Immune-related Adverse Events
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 1,000
- 试验地点
- 1
- 主要终点
- Incidence of immune-related adverse events
研究概览
简要总结
Immune checkpoint inhibitors (ICI) are among the most promising approaches to fighting cancer. However, a substantial percentage of patients experience off-target adverse effects in the form of mild to severe inflammation in different organs, commonly called immune-related adverse events (irAEs). irAEs can lead to treatment discontinuation, or can be life-threatening in extreme cases. The causes of irAEs are largely unknown and there are no reliable predictive biomarkers. The Montreal Immune-Related Adverse Events (MIRAE) study collects clinical information and biospecimens (blood, tissue, stool) from cancer patients treated with ICI to facilitate research on the identification of predictive biomarkers of irAEs, their causes, and the design of effective management strategies.
详细描述
Background:
During cancer development and progression, cancer cells evolve to evade natural anti-tumor immunity. One major pathway of immune evasion involves the engagement of co-inhibitory receptors present on the surface of T cells that modulate their activation status, and therefore their ability to directly or indirectly kill tumor cells. These receptors are known as immune checkpoint inhibitors (ICI). Blockade of ICI using antibodies leads to prolonged T cell activation and unleashes the anti-tumor activity of T cells. ICI treatment for cancer has led to unprecedented advances in cancer treatment by prolonging survival of patients with previously refractory cancers. Among these ICI, CTLA-4, PD-1 and PDL-1 inhibitors have been shown to be effective cancer immunotherapies, and many other ICIs are now in pre-clinical and clinical development.
Although ICI cancer therapy is overall well tolerated, off-target immune reactions targeting healthy cells or tissues called immune-related adverse events (irAEs) develop in a substantial percentage of patients limiting the use of ICI therapy. irAEs target range from mild to severe and fatal. Currently, there are no reliable predictive biomarkers for the wide spectrum of irAEs and their clinical management in severe cases involves discontinuation of ICI therapy.
The Montreal Immune-Related Adverse Events (MIRAE) study is a biobank that collects human biological specimens (e.g., tissue, blood, plasma, PBMCs, saliva, stool) and the associated clinical information from cancer patients treated with ICI with the purpose of promoting research to identify clinical and biological predictors and mechanisms of irAEs, evaluate the effects of immunomodulatory treatment of irAEs on tumor biology, and investigate treatment strategies to minimize irAEs.
Objectives:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •>= 18 years of age
- •cancer patients treated with ICI therapy (e.g., anti-CTLA-4, anti-PD-1, anti-PD-L1, and combinations)
- •patients with primary autoimmune or autoinflammatory diseases that resemble immune-related adverse events (irAEs)
- •healthy volunteers with non-inflammatory disorders, and without any history of cancer
排除标准
- •Participants not able to provide informed consent
结局指标
主要结局
Incidence of immune-related adverse events
时间窗: Up to 5 years
Biomarkers of irAE
时间窗: Up to 5 years
次要结局
未报告次要终点
研究者
Marie Hudson, MD
Marie Hudson, MD MPH FRCPC Principal Investigator, Rheumatologist, Division of Rheumatology and Department of Medicine, Jewish General Hospital and McGill University
Sir Mortimer B. Davis - Jewish General Hospital