Exhaustive Genetic and Immunological Characterization of Colon, Kidney and Liver Tumors to Define Potential Targets of Targeted and/or Immunomodulatory Therapies
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 150
- 试验地点
- 3
- 主要终点
- Sequencing of the exome and tumor RNA
研究概览
简要总结
Over the last 10 years, technological advances in molecular biology enabled a more accurate genomic characterization of tumors. For each tumor location, this led to the identification of subgroups with similar molecular characteristics. This identification allowed the development of targeted therapies and thus to improve the patient prognosis. This molecular characterization has also revealed the tumor heterogeneity. It may be the cause of treatment resistance and therefore of relapses. Additionally, tumor cells are in constant dialogue with their microenvironment composed of different immune or non immune cells. This microenvironment is now targeted in cancer treatment.
To date, there are few studies that combine a deep genomic characterization of both tumor and tumor microenvironment of the patient. Combining the two types of studies on the same tumor should help to define new therapeutic targets and should allow a combination of targeted and immunomodulatory therapies. To this end, our project is to conduct an exhaustive integrated exploratory analysis at genomic, transcriptomic and immunological levels of 3 tumor types (in colon, kidney and liver cancer).
详细描述
The design consists in recruiting 50 patients per tumor location (colon, kidney, liver). For colorectal and kidney cancers, a prospective enrollment will be done for patients who have consented to the study. A retrospective enrollment will be done for patients with liver cancer only and who have consented to a national biological resource center form with genetic study approval.
The tumor samples will be taken during surgery. Blood and tumors samples will be taken as part of the treatment.
In case of a accidental germline discovery a management by a genetic consulting will be proposed.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •for colorectal cancer group : patient with stage III colon carcinoma
- •for kidney cancer group : patient with primary clear cell carcinoma more than 4 cm
- •for liver cancer group : patient with advanced hepatocellular carcinoma : biopsy or resected BCLC (Barcelona Clinic Liver Cancer) stage B or C
- •patients who have consented to the study
排除标准
- •Patients receiving neoadjuvant therapy are not eligible
结局指标
主要结局
Sequencing of the exome and tumor RNA
时间窗: Day of surgery
Molecular classification of tumors
次要结局
- Quantification of lymphocytes T CD8 (activated/inhibited)(Inclusion and 4 weeks after surgery)
- Treg profile(Inclusion and 4 weeks after surgery)
- Immunophenotyping of intratumoral lymphocytes(Day of surgery)
- Densities of lymphocytes T CD8 (cluster of differentiation 8)(Day of surgery)
- Densities of macrophages M2 (CD68, CD163)(Day of surgery)
- Complement components assay(Inclusion and 4 weeks after surgery)
- Quantification of lymphoid structures in immune infiltrate : DC-Lamp (Dendritic cell-lysosomal associated membrane protein)/CD3(Day of surgery)
- Expression profile of immune and stromal metagenes(Day of surgery)
- MHC (major histocompatibility complex) peptide binding : Elispot(Inclusion and 4 weeks after surgery)
- Cytokine assay : Luminex(Inclusion and 4 weeks after surgery)
- Densities of fibroblasts (SMA)(Day of surgery)
- Quantification of lymphocytes T CD4 (activated/inhibited)(Inclusion and 4 weeks after surgery)
- Angiogenesis markers assay(Inclusion and 4 weeks after surgery)
- HLA (human leukocyte antigen) typing(Day of surgery)
- Quantification of lymphoid structures in immune infiltrate : CD20/CD3(Day of surgery)
- Transcriptomic profile of urinary RNAs(Inclusion)
研究者
Pierre Laurent-Puig
MD, PhD
European Georges Pompidou Hospital