Integrated Discovery of New Immuno-Molecular Actionable Biomarkers for Tumors With Immune-suppressed Environment
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 201
- 试验地点
- 1
- 主要终点
- Prognostic value of the tumor invasive biomarkers
研究概览
简要总结
The explosion of novel therapies targeting tumor mutations or immune molecules requests to define or better characterize the mutational profiles of tumors that are none or insufficiently explored so far. This is particularly the case for tumors arising in immune-suppressed individuals or environments which have been poorly, if any, analyzed so far with modern molecular methods. The goal of the translational research program, Ideation, is to define novel biomarkers such as the tumor mutational profiling and immunomutanome in such contexts and to compare the results obtained to those observed in immune competent individuals. In addition, this approach will allow to characterize novel key non-invasive diagnostic and prognostic biomarkers such as circulating tumoral DNA and cells. Altogether results will provide novel biomarkers to better adapt therapeutic strategies in these cancers, to monitor response to treatment as well as to define new molecular targets of potential therapeutic strategies.
详细描述
The main objective is to discover novel invasive and non-invasive immuno-molecular actionable biomarkers in rare but severe tumors arising in immune-suppressed compared for some tumors in immune-competent patients. Indeed, this tumors present a deficient immune environment, either due to the host acquired immune deficiency, i.e. transplantations or HIV infection, or because the diseased tissue belongs in an immune sanctuary as the brain. The primary hypothesis, in this context, is that these tumor mutational profiles and their changes during drug therapy must be influenced by the immune environment and response. This must lead to differences from similar tumors observed in immune-competent environments (immunocompetent individuals or tissues expressing immunity), responsible for: modification in the molecular targets for appropriate drugs ; alteration of tumor immunogenicity and of future immune-based therapies ; specific biomarkers for monitoring the response to drug therapy. The objectives of this program are to carry on invasive and non-invasive investigations in order to define the mutational profile of these free types of severe tumors, non-Hodgkin lymphoma (NHL), lung cancers and gliomas arising in hosts or tissues with altered immunity. These investigations will lead to : identify novel invasive and non-invasive biomarkers for predicting and evaluating efficacy of future personalized and immune-based therapies; compare tumors from immune-suppressed and immune-competent hosts; discover hot spots of tumoral mutations as mechanisms of tumors resistance, new molecular targets for future molecular and immune-bases therapeutic strategies; define the tumor immunomutanome as a score of neo-epitopes predicting: tumor immunogenicity, disease outcome and efficacy of immunotherapies; detect non-invasive tumoral biomarkers from liquid biopsies based on Circulating tumoral DNA and Circulating tumoral Cells to facilitate future diagnosis and monitoring of such tumors; identify biomarkers of tumor escape or resistance to treatments.
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.
- •Followed at Pitié-Salpêtrière hospital, Tenon hospital, Henri Mondor hospital, Saint-Louis hospital or intercommunal hospital center of Créteil
- •Histological diagnosis confirmed of:
- •Non-small cell lung cancer (adenocarcinoma, squamous cell, large cells) related to HIV, or
- •Immunocompetent non-small cell lung cancer (adenocarcinoma, squamous cell, large cells), or
- •Non-Hodgkin's lymphoma (NHL): HIV-related NHL, post-transplant lymphoproliferation (LPT) according to WHO (World Health Organization) 2016 classification, primary CNS (central nervous system) lymphoma (LPS), or
- •Primary CNS lymphoma
- •Immunocompetent NHL: diffuse large B cell lymphoma (ABC or GC)
- •Naïve cancer treatment (except for the specific case of gliomas with certain or possible activation of MAPK (Mitogen-activated protein kinases) and MMR (Mismatch Repair) inactivation).
- •Cancer undergoing surgery for excision or a large biopsy (pleural biopsy under video-thoracoscopy, mediastinoscopy, biopsy lymph node excision or cutaneous or cerebral metastasis).
- •For patients with NSCLC: hemoglobin level> 9 g / dL; for patients with NHL or glioma: hemoglobin > 7 g / dL.
- •Weight ≥ 48 kg.
- •Informed consent to participation signed before carrying out any specific procedure of the study.
- •Affiliation to the French social security system.
排除标准
- •Other cancer than those in the study:
- •For NHL after transplantation: marginal zone NHL, follicular NHL, mantle cell NHL, lymphoplasmocytic NHL (non-WHO lymphoma as LPT)
- •For HIV-related LPTs and NHLs: LPS
- •For LPT: tumor EBV status unknown
- •For immunocompetent NHL: other NHL than diffuse large B cell lymphoma
- •For lung cancers: small cell lung cancer
- •Absence of tumor material, blood or saliva samples taken before the start of chemotherapy (except for the specific case of gliomas with certain or possible activation of MAPK and MMR inactivation)
- •Major under guardianship or curatorship
结局指标
主要结局
Prognostic value of the tumor invasive biomarkers
时间窗: at Day 0
Analyze of the tumor biomarkers on frozen biopsy for the three types of cancer (NHL, lung cancer and glioma)
次要结局
- Prognostic value of the tumor non invasive biomarkers(at Day 0, Month 3 and Month 6)
- Determination of tumoral biomarkers(at Day 0)
- Prognostic value of the tumor non-invasive biomarkers(at Day 0, Month 3 and Month 6)