Clinical trial NCT03265496: Correlation Between Tissue and Plasmatic EGFR in CBNPC With EGFR Mutation or Predictive Factor of EGFR Mutation
Official title: Correlation Between Tissue and Plasmatic EGFR in CBNPC With EGFR Mutation or Predictive Factor of EGFR Mutation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Nsclc
Lead sponsor: Centre Oscar Lambret
Sponsor class: OTHER
Collaborators: name: University Hospital, Lille
First posted: 2017-08-29
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At diagnostic. NGS.
timeFrame: Baseline
Secondary outcomes:
measure: Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At diagnostic. rtPCR.
timeFrame: Baseline
measure: Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At diagnostic. dPCR.
timeFrame: Baseline
measure: Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At disease progression. NGS.
timeFrame: From Baseline to disease progression, up to 2 years
measure: Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At disease progression. rtPCR.
timeFrame: From Baseline to disease progression, up to 2 years
measure: Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At disease progression. dPCR.
timeFrame: From Baseline to disease progression, up to 2 years
measure: Incidence of oncogenic mutation for patients with predictive factors
timeFrame: From Baseline to disease progression, up to 2 years
measure: Predictive value of ctDNA during treatment with EGFR targeting therapy.
timeFrame: From Baseline to disease progression, up to 2 years
measure: Mutations on ctDNA and tumor biopsy.
timeFrame: From Baseline to disease progression, up to 2 years
Other outcomes:
measure: Mutation in ctDNA
timeFrame: From Baseline to disease progression, up to 2 years
measure: expression pattern of tumor grade and resistance
timeFrame: From Baseline to disease progression, up to 2 years
Locations:
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lille
country: France
facility: CHRU Lille
Study officials:
affiliation: Centre Oscar Lambret
name: Kotecki Nuria, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHRU LILLE
name: Cortot Alexis, Pr
role: PRINCIPAL_INVESTIGATOR
References: