BIOREN (Predictive BIOmarkers in Metastatic RENal Cancer) - A Translational Study on Immunotherapy for Metastatic Renal Cancer
试验速览
- 阶段
- 不适用
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Evaluation of Tregs function on peripheral blood/neoplastic tissue from mRCC patients undergoing nivolumab treatment
研究概览
简要总结
The BIOREN project aims are to characterize the genetic background of renal cell carcinomas and their immune environment, to try and identify biomarkers of response and to better understand the mechanisms of resistance to nivolumab in renal cancer.
详细描述
Around 338,000 new cases of renal cell carcinoma (RCC) are diagnosed worldwide per year (1). RCC is one of the most immune responsive human cancers. For a long time the only available treatment were high-dose IL-2 and IFN-α with only a few patients achieving durable responses. Clinical trials conducted in the past 15 years have led to the approval of several anti-angiogenic treatments, mainly vascular endothelial growth factor receptor (VEGFR) inhibitors and mTOR inhibitors. Currently most patients receive first line anti-VEGF therapy.
Recently a better understanding of the mechanisms by which tumours evade the immune system has led to the development of checkpoint inhibitors, such as anti CTLA-4, anti-PD-1 and anti-PD-L1 antibodies that have been tested in various tumour types.
Recently, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved the human IgG4 anti-PD1 monoclonal antibody, nivolumab, for advanced/metastatic clear cell RCC (ccRCC) patients who have received prior antiangiogenic therapy. PD-1 is a key immune-checkpoint receptor (ICR) expressed by activated T cells, which mediates immunosuppression primarily in peripheral tissues, where T cells may encounter the immunosuppressive PD-1 ligands, PD-L1 (B7-H1) and PD-L2(B7-DC) on tumour cells, stromal cells or both.
Despite encouraging results, the clinical response to anti-PD1 is not as wide as expected and there are not any biomarkers 1) that are able to predict which patients will respond and 2) that predict response to nivolumab in patients with ccRCC.
BIOREN is a translational, prospective, observational 3-cohort study.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years-old.
- •Histology proven locally advanced (unresectable) or metastatic clear cell renal cell carcinoma (mccRCC).
- •Starting 2nd or 3rd line of treatment with nivolumab, everolimus, axitinib or cabozantinib as per summaries of product characteristics (SmPC) or 1st line treatment with sunitinib or pazopanib or receiving 2nd or 3rd line of treatment with nivolumab
- •Signed informed consent.
排除标准
- •Psychological, familial, sociological, geographical conditions that would limit compliance with study protocol requirements.
- •Pregnant or breastfeeding woman
结局指标
主要结局
Evaluation of Tregs function on peripheral blood/neoplastic tissue from mRCC patients undergoing nivolumab treatment
时间窗: Evolution of percentage of CD4+CD25+ CD127low FOXP3+ cells between inclusion and up to 24 months
Ex vivo effect of CXCR4 antagonists (PCT/IB2011/000120/ EP2528936B1/ US2013/0079292A1) and other Tregs targets antagonists (ICOS, CD39/CD73) or agonists (TLR7L) as putative anti-PD1 resistance mechanisms
次要结局
- Evaluation of NK function/cytotoxicity on peripheral blood/neoplastic tissue from mRCC patients undergoing nivolumab treatment(Evolution between inclusion and up to 24 months)
- Identification of response biomarkers(Up to 24 months)
- Exploration of the biological rationale for coupling CXCR4 antagonist with anti-PD-1 in in vivo models of renal cancer (mice models).(Up to 24 months)
- Identification of biomarkers of response(Evolution between inclusion and up to 24 months)