Exhaustive Genetic and Immunological Characterization of Colon, Kidney and Liver Tumors

Colorectal Adenocarcinoma Clinical Trial

— ExhauCRF  

Official title:

Exhaustive Genetic and Immunological Characterization of Colon, Kidney and Liver Tumors to Define Potential Targets of Targeted and/or Immunomodulatory Therapies

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03149523
• Other study ID #: CARPEM_ExhauCRF
• Status: Not yet recruiting
• Phase: N/A
• First received: May 9, 2017
• Last updated: May 16, 2017
• Start date: May 2017
• Est. completion date: April 2019

Study information

• Verified date: May 2017
• Source: European Georges Pompidou Hospital
• Contact: Pierre Laurent-Puig, MD, PhD
• Phone: 00331 42 86 20 81
• Email: pierre.laurent-puig[@]parisdescartes.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 150
• Est. completion date: April 2019
• Est. primary completion date: April 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma, Hepatocellular
• Carcinoma, Renal Cell
• Colorectal Adenocarcinoma
• Hepatic Carcinoma
• Kidney Adenocarcinoma
• Liver Neoplasms

Locations

Country	Name	City	State
France	AP-HP Jean Verdier Hospital	Bondy
France	AP-HP Cochin Hospital	Paris
France	AP-HP European Georges Pompidou Hospital	Paris

Sponsors (2)

Lead Sponsor	Collaborator
European Georges Pompidou Hospital	Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sequencing of the exome and tumor RNA	Molecular classification of tumors	Day of surgery
Secondary	HLA (human leukocyte antigen) typing	Prediction of neoantigens implicated in the intratumoral immune response	Day of surgery
Secondary	Immunophenotyping of intratumoral lymphocytes	Immunologic characteristic of tumors	Day of surgery
Secondary	Densities of lymphocytes T CD8 (cluster of differentiation 8)	Immunologic characteristic of tumors	Day of surgery
Secondary	Densities of macrophages M2 (CD68, CD163)	Immunologic characteristic of tumors	Day of surgery
Secondary	Densities of fibroblasts (SMA)	Immunologic characteristic of tumors	Day of surgery
Secondary	Quantification of lymphoid structures in immune infiltrate : DC-Lamp (Dendritic cell-lysosomal associated membrane protein)/CD3	Immunologic characteristic of tumors	Day of surgery
Secondary	Quantification of lymphoid structures in immune infiltrate : CD20/CD3	Immunologic characteristic of tumors	Day of surgery
Secondary	Expression profile of immune and stromal metagenes	Immunologic characteristic of tumors	Day of surgery
Secondary	Quantification of lymphocytes T CD4 (activated/inhibited)	Immunologic characteristic of circulating cells	Inclusion and 4 weeks after surgery
Secondary	Quantification of lymphocytes T CD8 (activated/inhibited)	Immunologic characteristic of circulating cells	Inclusion and 4 weeks after surgery
Secondary	Treg profile	Immunologic characteristic of circulating cells	Inclusion and 4 weeks after surgery
Secondary	MHC (major histocompatibility complex) peptide binding : Elispot	Immunologic characteristic of circulating cells	Inclusion and 4 weeks after surgery
Secondary	Cytokine assay : Luminex	Immunologic characteristic of circulating cells	Inclusion and 4 weeks after surgery
Secondary	Angiogenesis markers assay	Immunologic characteristic of circulating cells	Inclusion and 4 weeks after surgery
Secondary	Complement components assay	Immunologic characteristic of circulating cells	Inclusion and 4 weeks after surgery
Secondary	Transcriptomic profile of urinary RNAs	Expression profile of immune gene in urine	Inclusion