LIquid BIopsies in Patients Presenting Non-small Cell Lung Cancer

Carcinoma, Non-Small-Cell Lung Clinical Trial

— LIBIL  

Official title:

Liquid Biopsies in Patients With Advanced Non-small Cell Lung Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02511288
• Other study ID #: ET15-076 LIBIL
• Status: Recruiting
• Start date: July 2015
• Est. completion date: December 2026

Study information

• Verified date: October 2021
• Source: Centre Leon Berard
• Contact: Pierre Saintigny, MD, PhD
• Email: pierre.saintigny[@]lyon.unicancer.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this project is to characterize the genetic profile of patients with advanced stage IIIB/IV non-small cell lung cancer (NSCLC) using liquid biopsies

Description:

Lung cancers are the first cause of death by cancer in the world. The majority of these patients are diagnosed at a late stage, non-eligible to a curative treatment. Due to tumoral genomic identification, it has been possible to classify NSCLC in molecular subtypes according to molecular abnormalities detection called "drivers" which can be targeted using an appropriate treatment. This change modifies the standard treatments from the very first line of treatment particularly for patients having an EGFR mutation or an ALK or ROS1 rearrangement, with a significant benefit of progression free survival. The French NCI (INCa) recommends to identify genomic alterations of a genes panel including EGFR, KRAS, BRAF, HER2, ALK and ROS1 as well as mutations in MET exon 14. However, all the patients who benefit from a targeted therapy develop resistance after a mean duration of 10-12 months after starting the treatment. In case of progression, the tumour genetic analysis through new biopsies, enables to identify these mechanisms and then to determine if the patient can benefit or not from a third generation molecule active on these mechanisms, and to have a better understanding of the disease evolution.

The detection of these alterations is routinely performed using tissular biopsies but in 10 to 20% of the cases, it is not possible.

The detection of these molecular abnormalities in the plasma, called " liquid biopsy " is a valuable non-invasive complementary approach for these patients. It is presently used in routine for detecting the EGFR mutations at diagnosis as well as for searching EGFR T790M mutation for resistant patients.

The liquid biopsies enable to detect circulating tumoral DNA.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 900
• Est. completion date: December 2026
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

COHORT 1

Inclusion Criteria:

• Patients with histologically confirmed advanced non-small-cell lung carcinoma (stage IIIB/IV) regardless of the mutation status

• Inclusion at the time of diagnostic

• Realization of tumor biopsy at the institution (Centre Léon Bérard) or outside the institution with an available histopathological report

• Age = 18 years

• Covered by a health insurance

• Signed consent

Exclusion Criteria:

• Patients treated before their liquid biopsy

COHORT 2 Inclusion criteria

• Patients with histologically confirmed advanced non-small-cell lung carcinoma (stage IIIB/IV) with one of the following molecular anomalies: Epidermal Growth Factor Receptor (EGFR), B-Raf proto oncogene (BRAF) or Human Epidermal Growth Factor Receptor-2 (HER2) mutations, Anaplatsic Lymphoma Kinase (ALK) or ROS porto-oncogene 1 (ROS1) translocation, Mesenchymal-epithelial transition factor (MET) amplification, RET rearrangement.

• Inclusion at the time of diagnosis

• Realization of tumor biopsy at the institution (Centre Léon Bérard) or outside the institution with an available histopathological report

• Age = 18 years

• Covered by a health insurance

• Signed consent

COHORT 3 Inclusion criteria

• Patients with histologically confirmed advanced non-small-cell lung carcinoma (stage IIIB/IV) whatever the mutational or PD-L1 status.

• Inclusion at the time of immunotherapy treatment initiation (1st or 2nd line)

• Realization of tumor biopsy at the institution (Centre Léon Bérard) or outside the institution with an available histopathological report

• Age = 18 years

• Covered by a health insurance

• Signed consent

Exclusion criteria

• Initiation of immunotherpy before their liquid biopsy

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Locations

Country	Name	City	State
France	Centre Hospitalier Annecy Genevois	Annecy
France	CH Fleyriat	Bourg-en-Bresse
France	Hôpital Louis Pradel	Bron
France	CHU Grenoble Alpes	Grenoble
France	Centre Léon Bérard	Lyon
France	CHRU de Saint-Etienne	Saint-Priest-en-Jarez
France	Institut de Cancérologie Lucien Neuwirth	Saint-Priest-en-Jarez
France	Hôpital Nord Ouest	Villefranche-sur-Saône

Sponsors (1)

Lead Sponsor	Collaborator
Centre Leon Berard

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of the genetic profile in advanced or metastatic NSCLC patients using liquid biopsies (circulating tumoral DNA)	Technique: ddPCR + targeted NGF, whole exome sequencing	5 years
Secondary	Identification of genetic biomarkers (or molecular profiles) having a potential predictive value in the treatments response	Techniques: ddPCR + targeted NGF, whole exome sequencing	5 years
Secondary	Detection of the ALK and ROS1 genes translocations in the circulating DNA	Techniques: ddPCR + targeted NGF, whole exome sequencing	5 years
Secondary	Evaluation of the liquid biopsies role in the tumoral monitoring	Correlation between mutated allelic fractions or expression's modification with the treatment response. Techniques: ddPCR + targeted NGF, whole exome sequencing	5 years
Secondary	Evaluation of genomic and transcriptomic factors detectable in the plasma, associated to the immunotherapy response	Correlation between transcriptomic and genomic factors and response to immunotherapy. Techniques: ddPCR + targeted NGF, whole exome sequencing	5 years
Secondary	Evaluation of the spatial and temporal tumor heterogeneity under targeted therapy treatment	Techniques: ddPCR + targeted NGF, whole exome sequencing	5 years
Secondary	Evaluation of the miRNAs' expression in plasma as an epigenetic factor associated to treatments response	Correlation between miRNAS expression in plasma and treatment's efficacy. Techniques: miRNAs profiling using HTG technology	5 years
Secondary	Circulating tumoral cells isolation and analysis to determine the role of non-genomic and/or phenotypic factors in the treatments response.	Single cell isolation technology	5 years
Secondary	Evaluation of the resistance mechanisms to targeted therapies	Technique: ddPCR + targeted NGF, whole exome sequencing	5 years