Exhaustive Genetic and Immunological Characterization of Colon, Kidney and Liver Tumors
- Conditions
- Kidney AdenocarcinomaHepatic CarcinomaColorectal Adenocarcinoma
- Registration Number
- NCT03149523
- Lead Sponsor
- European Georges Pompidou Hospital
- Brief Summary
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).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 150
- 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
- Patients receiving neoadjuvant therapy are not eligible
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Sequencing of the exome and tumor RNA Day of surgery Molecular classification of tumors
- Secondary Outcome Measures
Name Time Method Quantification of lymphocytes T CD8 (activated/inhibited) Inclusion and 4 weeks after surgery Immunologic characteristic of circulating cells
Treg profile Inclusion and 4 weeks after surgery Immunologic characteristic of circulating cells
Cytokine assay : Luminex Inclusion and 4 weeks after surgery Immunologic characteristic of circulating cells
Immunophenotyping of intratumoral lymphocytes Day of surgery Immunologic characteristic of tumors
Densities of lymphocytes T CD8 (cluster of differentiation 8) Day of surgery Immunologic characteristic of tumors
Densities of macrophages M2 (CD68, CD163) Day of surgery Immunologic characteristic of tumors
Complement components assay Inclusion and 4 weeks after surgery Immunologic characteristic of circulating cells
MHC (major histocompatibility complex) peptide binding : Elispot Inclusion and 4 weeks after surgery Immunologic characteristic of circulating cells
Quantification of lymphoid structures in immune infiltrate : DC-Lamp (Dendritic cell-lysosomal associated membrane protein)/CD3 Day of surgery Immunologic characteristic of tumors
Expression profile of immune and stromal metagenes Day of surgery Immunologic characteristic of tumors
Densities of fibroblasts (SMA) Day of surgery Immunologic characteristic of tumors
Quantification of lymphocytes T CD4 (activated/inhibited) Inclusion and 4 weeks after surgery Immunologic characteristic of circulating cells
Angiogenesis markers assay Inclusion and 4 weeks after surgery Immunologic characteristic of circulating cells
HLA (human leukocyte antigen) typing Day of surgery Prediction of neoantigens implicated in the intratumoral immune response
Quantification of lymphoid structures in immune infiltrate : CD20/CD3 Day of surgery Immunologic characteristic of tumors
Transcriptomic profile of urinary RNAs Inclusion Expression profile of immune gene in urine
Trial Locations
- Locations (3)
AP-HP European Georges Pompidou Hospital
🇫🇷Paris, France
AP-HP Jean Verdier Hospital
🇫🇷Bondy, France
AP-HP Cochin Hospital
🇫🇷Paris, France