Clinical trial NCT02511288: LIquid BIopsies in Patients Presenting Non-small Cell Lung Cancer
Official title: Liquid Biopsies in Patients With Advanced Non-small Cell Lung Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Hematologic test
Liquid biopsy
Lead sponsor: Centre Leon Berard
Sponsor class: OTHER
First posted: 2015-07-30
Enrollment: 900
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with advanced NSCLC

Brief 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Identification of the genetic profile in advanced or metastatic NSCLC patients using liquid biopsies (circulating tumoral DNA)
timeFrame: 5 years
Secondary outcomes:
measure: Identification of genetic biomarkers (or molecular profiles) having a potential predictive value in the treatments response
timeFrame: 5 years
measure: Detection of the ALK and ROS1 genes translocations in the circulating DNA
timeFrame: 5 years
measure: Evaluation of the liquid biopsies role in the tumoral monitoring
timeFrame: 5 years
measure: Evaluation of genomic and transcriptomic factors detectable in the plasma, associated to the immunotherapy response
timeFrame: 5 years
measure: Evaluation of the spatial and temporal tumor heterogeneity under targeted therapy treatment
timeFrame: 5 years
measure: Evaluation of the miRNAs' expression in plasma as an epigenetic factor associated to treatments response
timeFrame: 5 years
measure: Circulating tumoral cells isolation and analysis to determine the role of non-genomic and/or phenotypic factors in the treatments response.
timeFrame: 5 years
measure: Evaluation of the resistance mechanisms to targeted therapies
timeFrame: 5 years
Other outcomes:
Locations:
city: Annecy
country: France
facility: Centre Hospitalier Annecy Genevois
city: Bourg-en-Bresse
country: France
facility: CH Fleyriat
city: Bron
country: France
facility: Hôpital Louis Pradel
city: Grenoble
country: France
facility: CHU Grenoble Alpes
city: Lyon
country: France
facility: Centre Léon Bérard
city: Saint-Priest-en-Jarez
country: France
facility: CHRU de Saint-Etienne
city: Saint-Priest-en-Jarez
country: France
facility: Institut de Cancérologie Lucien Neuwirth
city: Villefranche-sur-Saône
country: France
facility: Hôpital Nord Ouest
Study officials:
affiliation: pierre.saintigny@lyon.unicancer.fr
name: Pierre Saintigny, MD, PhD
role: STUDY_DIRECTOR
References: