Implementing Circulating Tumor DNA Analysis at Initial Diagnosis to Improve Management of Advanced NSCLC Patients

Study Overview
=================
Brief Summary
-----------------
Multicenter prospective cohort study aiming to evaluate the detection rate of EGFR gene mutation in patients with advanced NSCLC in a real-word clinical setting, based on liquid biopsy and tissue analyses.

Detailed Description
-----------------
This a multicenter prospective cohort study. This study will be proposed to newly diagnosed advanced NSCLC patients. For included patients, archived paraffin embedded tumor tissue will be used for sequencing ; and blood sample will be collected for research purpose (plasma DNA collection and sequencing). Both tissue and liquid biopsy samples will follow usual processes and will be sent to the Molecular Pathology laboratory of the Investigation center.

Official Title
-----------------
Implementing Circulating Tumor DNA Analysis at Initial Diagnosis to Improve Management of Advanced Non-small Cell Lung Cancer Patients (NSCLC)

Conditions
-----------------
Non Small Cell Lung Cancer, Advanced Solid Tumor

Intervention / Treatment
-----------------
* Diagnostic Test: EGFR gene mutation analysis on liquid biopsy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female patients aged ≥ 18 years at time of proposal study, Histologically confirmed non-small cell lung carcinoma, No previous treatment for NSCLC, Indication to EGFR status determination following HAS recommendation, Voluntary signed and dated written informed consent prior to any study specific procedure Patients with a social security in compliance with the French Law. Exclusion Criteria: Treatment for advanced NSCLC started before liquid biopsy sampling. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Interventional Model Description: This is a multicentric prospective cohort in which newly diagnosed advanced NSCLC patients will be included. For all patients, both tumor and liquid biopsy samples will be used for sequencing and detection of EGFR gene mutation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All patients<br>For all patients, blood sample will be collected at inclusion (liquid biopsy) for sequencing. As per standard management, for all of these patients, EGFR gene mutation will be also analyzed on archived tumor sample. | Diagnostic Test: EGFR gene mutation analysis on liquid biopsy<br>* Blood samples will be collected at inclusion for plasma DNA collection and analysis.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the detection rate of patients with an EGFR actionable alteration when using the combination of two diagnostic procedures which include liquid biopsy analysis (by droplet digital PCR or allele specific PCR) and tissue analysis | Resuls of each EGFR diagnostic procedure will be categorized as EGFR positive in case of the presence of an EGFR actionnable alteration ; as EGFR negative in case of the absence of an EGFR actionnable alteration ; or nor interpretable. A patient will be considered to have an EGFR actionable alteration if the mutation has been detected on the sequencing of tumor tissue OR if it has been detected on the liquid biopsy procedure | within 3 weeks after signature of informed consent | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The detection rate of patients with an EGFR actionable alteration based on the use of liquid biopsy analysis only | A patient will be considered to have an EGFR actionable alteration (EGFR+) detected by the liquid biopsy analysis if an EGFR actionable alteration is identified based on the liquid biopsy analysis | within 3 weeks after signature of informed consent | 
| The detection rate of patients with an EGFR actionable alteration based on tissue analysis only | A patient will be considered to have an EGFR actionable alteration (EGFR+) detected by tissue analysis if an EGFR actionable alteration is identified based on the sequencing of tumor tissue | within 3 weeks after signature of informed consent | 
| The concordance and discordance rates between the two procedures | Concordance is defined whenever results of both techniques are identical (i.e. EGFR+ for both techniques or EGFR- for both techniques). Discordance is defined whenever results of both techniques are different. | within 3 weeks after signature of informed consent | 
| The failure rate for each procedure and reasons of failure (insufficient DNA quantity, poor DNA quality, insufficient tissue quantity, poor tissue quality, analytical failure) | • Failure of a procedure (sequencing of tumor tissue or liquid biopsy) is defined whenever the procedure fails to provide an interpretable result (Reasons for failure will be collected, i.e. insufficient DNA quantity, poor DNA quality, insufficient DNA/tissue quantity, poor DNA/tissue quality, analytical failure) | within 3 weeks after signature of informed consent | 
| Delay to obtain sequencing results | The delay between the date of the signature of the informed consent and the date of availability of the results for each procedure | within 3 weeks after signature of informed consent | 
| Delay for treatment initiation | The delay between the date of sample collection and the date of treatment initiation | within 3 months after signature of informed consent | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
non-small cell lung cancer, EGFR detection, liquid biopsy