Clinical trial NCT03149523: Exhaustive Genetic and Immunological Characterization of Colon, Kidney and Liver Tumors
Official title: Exhaustive Genetic and Immunological Characterization of Colon, Kidney and Liver Tumors to Define Potential Targets of Targeted and/or Immunomodulatory Therapies
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Colorectal Adenocarcinoma
Hepatic Carcinoma
Kidney Adenocarcinoma
Keywords: exhaustive genetic and immunological analyses
targeted therapies
colon cancer
kidney cancer
liver cancer
immunological tumor microenvironment
tumor microenvironment heterogeneity
Lead sponsor: European Georges Pompidou Hospital
Sponsor class: OTHER
Collaborators: name: Assistance Publique - Hôpitaux de Paris
First posted: 2017-05-11
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with colorectal, kidney or liver cancers.

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* Patients receiving neoadjuvant therapy are not eligible

Primary outcomes:
measure: Sequencing of the exome and tumor RNA
timeFrame: Day of surgery
Secondary outcomes:
measure: HLA (human leukocyte antigen) typing
timeFrame: Day of surgery
measure: Immunophenotyping of intratumoral lymphocytes
timeFrame: Day of surgery
measure: Densities of lymphocytes T CD8 (cluster of differentiation 8)
timeFrame: Day of surgery
measure: Densities of macrophages M2 (CD68, CD163)
timeFrame: Day of surgery
measure: Densities of fibroblasts (SMA)
timeFrame: Day of surgery
measure: Quantification of lymphoid structures in immune infiltrate : DC-Lamp (Dendritic cell-lysosomal associated membrane protein)/CD3
timeFrame: Day of surgery
measure: Quantification of lymphoid structures in immune infiltrate : CD20/CD3
timeFrame: Day of surgery
measure: Expression profile of immune and stromal metagenes
timeFrame: Day of surgery
measure: Quantification of lymphocytes T CD4 (activated/inhibited)
timeFrame: Inclusion and 4 weeks after surgery
measure: Quantification of lymphocytes T CD8 (activated/inhibited)
timeFrame: Inclusion and 4 weeks after surgery
measure: Treg profile
timeFrame: Inclusion and 4 weeks after surgery
measure: MHC (major histocompatibility complex) peptide binding : Elispot
timeFrame: Inclusion and 4 weeks after surgery
measure: Cytokine assay : Luminex
timeFrame: Inclusion and 4 weeks after surgery
measure: Angiogenesis markers assay
timeFrame: Inclusion and 4 weeks after surgery
measure: Complement components assay
timeFrame: Inclusion and 4 weeks after surgery
measure: Transcriptomic profile of urinary RNAs
timeFrame: Inclusion
Other outcomes:
Locations:
city: Bondy
country: France
facility: AP-HP Jean Verdier Hospital
city: Paris
country: France
facility: AP-HP Cochin Hospital
city: Paris
country: France
facility: AP-HP European Georges Pompidou Hospital
Study officials:
References: