Correlation Between Tissue and Plasmatic EGFR in CBNPC With EGFR Mutation or Predictive Factor of EGFR Mutation

Study Overview
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Brief Summary
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Condorde main objective is to evaluate the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed on ctDNA after liquid biopsy. EGFR status will be assessed by real time PCR (rtPCR), digital PCR (dPCR) and Next Generation Sequencing (NGS) in patients with chemotherapy naive lung carcinoma.

Detailed Description
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Newest therapeutic breakthrough are often based on molecular analysis of tumoral tissue before treatment initiation or after emergence of resistance. Tumoral tissue is commonly obtained by biopsy. However, tumor biopsy is an invasive, scarcely repeatable and costly technics. Moreover, tumor samples, obtained by biopsy, doesn't represent tumor heterogeneity and cannot inform about tumor evolution over time. Recent improvement have been done in detection and characterization of blood circulating tumoral DNA (ctDNA). ctDNA reach regularly the blood stream after tumoral cell apoptosis or necrosis and could be extract and sequenced by some molecular biology technics such as real time PCR (rtPCR), digital PCR (dPCR) or next generation sequencing (NGS). Interesting, Several studies demonstrate that some genomic alterations of solid cancer can be characterized after sequencing of ctDNA. Other experiments pointed that ctDNA level could be linked to tumor stage and patient prognostic. These progress lead to the development of a new non invasive method for extraction of ctDNA called liquid biopsy (LB). LB could be useful for monitor tumoral genotype, assess tumor response to treatment and detect residual tumor cells after curative treatment. Moreover LB could be an essential method for study of tumor cells molecular alterations mechanisms during targeted cancer therapies, when clinical resistance occurs. Non-small cell lung cancer (NSCLC) is the most frequently diagnosticated type of lung cancer. Regular first line chemotherapy is based on the use of platinum salts. However, some mutations in the EGFR gene could add sensitivity of NSCLC to tyrosine kinase inhibitors such as gefitinib, erlotinib or afatinib. Consequently, the search for molecular mutations in genome of NSCLC cells is of prior interest for patients with clinically advanced NSCLC. Recently, some studies demonstrate that mutational EGFR status of NSCLC was sharply correlated between tumoral tissue, obtained by classical biopsy, and ctDNA, collected by liquid biopsy. These results provide promising data encouraging the use of LB for study of NSCLC ctDNA. However some experimentations are needed to ensure these data. For that reason, CONCORDE clinical trial will evaluate the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. EGFR status will be assessed by real time PCR (rtPCR), digital PCR (dPCR) and Next Generation Sequencing (NGS) in patients with chemotherapy naive lung carcinoma.

Official Title
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Correlation Between Tissue and Plasmatic EGFR in CBNPC With EGFR Mutation or Predictive Factor of EGFR Mutation

Conditions
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Nsclc

Intervention / Treatment
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* Procedure: Clinical exam
* Procedure: Liquid biopsy
* Procedure: Diagnostic exam
* Drug: 1st line treatment
* Procedure: tumor evaluation
* Biological: Biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years Metastatic lung carcinoma With: - EGFR gene mutation Or at least 2 predictive factors of addictive mutation (Women, non smocking or cessation > 3 years, Asiatic, lung adenocarcinoma) Eligible for 1st line treatment Performance status ≤ 3 Available tumor sample or tumor reachable for biopsy With informed and signed consent Affiliation to the National Social Security System Exclusion Criteria: Previous radiotherapy treatment in months preceding initials samples Pregnant or breastfeeding women Patient not able to give consent or unwilling to provide consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: study procedure<br>Clinical exam. Liquid biopsy. Diagnostic exam (biopsy and imagery). 1st line treatment. tumor evaluation. Biopsy | Procedure: Clinical exam<br>* Clinical exam is performed before treatment start<br>Procedure: Liquid biopsy<br>* Liquid biopsy will be performed at baseline and every 3 cycles of chemotherapy until progression disease<br>Procedure: Diagnostic exam<br>* Diagnostic exam (biopsy and imagery exam) will be performed at baseline if not previously done or incompletely done.<br>Drug: 1st line treatment<br>* 1st line chemotherapy (chemotherapy or EGFR targeted therapy) will be performed until progression disease.<br>* Other names: 1st line chemotherapy;Procedure: tumor evaluation<br>* Tumor evaluation will be performed every 3 cycles of chemotherapy<br>Biological: Biopsy<br>* Biopsy will be performed at the end of study, after progression disease, if a mutation of EGFR is detected in tumor DNA.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At diagnostic. NGS. | For patient with mutant EGFR. Evaluate, by next generation sequencing at diagnostic, the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At diagnostic. rtPCR. | For patient with mutant EGFR. Evaluate, by real time PCR at diagnostic, the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. | Baseline | 
| Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At diagnostic. dPCR. | For patient with mutant EGFR. Evaluate, by digital PCR at diagnostic, the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. | Baseline | 
| Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At disease progression. NGS. | For patient with mutant EGFR. Evaluate, by Next Generation Sequencing at disease progression, the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. | From Baseline to disease progression, up to 2 years | 
| Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At disease progression. rtPCR. | For patient with mutant EGFR. Evaluate, by rtPCR at disease progression, the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. | From Baseline to disease progression, up to 2 years | 
| Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At disease progression. dPCR. | For patient with mutant EGFR. Evaluate, by dPCR at disease progression, the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. | From Baseline to disease progression, up to 2 years | 
| Incidence of oncogenic mutation for patients with predictive factors | To evaluate the incidence of oncogenic mutations in populations with clinical predictive factors of these mutations. | From Baseline to disease progression, up to 2 years | 
| Predictive value of ctDNA during treatment with EGFR targeting therapy. | To assess the predictive value of mutant ctDNA during treatment with EGFR targeting therapy. | From Baseline to disease progression, up to 2 years | 
| Mutations on ctDNA and tumor biopsy. | To search for mutations leading to treatment resistance on ctDNA and tumor biopsy at proved disease progression | From Baseline to disease progression, up to 2 years |