Lung CancerCELTICSNCT04624373
Genotyping of Ebus-tbna Supernant Cell-free Dna in Nsclc
An observational study of Lung Cancer, run by University Hospital, Toulouse at 1 site in France.
Trial summary
The wide uptake of "liquid biopsy" diagnostics in the care of advanced cancer patients highlights the desire for improved access to tumor allowing accurate tumor genotyping (1). Genotyping of plasma cfDNA is now routine for detection of EGFR driver mutations at diagnosis of NSCLC, or for detection of the EGFR T790M… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Lung Cancer
- What is being tested?
- Molecular analysis of surnatant
- How many people
- 50 participants
- Where
- 1 siteFrance
- Study dates
- 1 Apr 2021to 31 Dec 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients will be recruited in our Department in Toulouse University Hospital, during appointment needed for information and planning of the EBUS-TBNA procedure.
Who may be able to join
- Age > 18 years-old
- Patients planned for an EBUS-TBNA for
- Suspicion of stage IV lung cancer (PET+ mediastinal node(s)) (Cohort 1)
- Stage IV NSCLC with an EGFR, BRAF, HER2, MET mutation or ALK, RET or ROS1 rearranged NSCLC and acquired resistance to targeted therapy (Cohort 2)
- Performance status 0-3
- Informed consent
Who cannot join
- Refusal to participate
- Patient under legal tutelage
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Nicolas Guibert
Toulouse
Nicolas Guibert, 5 67 77 81 60 ext. +33, guibert.n@chu-toulouse.fr
About this study
Official title: Molecular Analysis of the Surnantant of Echoguidated Bronchoscopic Cytopunctions in Lung Cancer
The wide uptake of "liquid biopsy" diagnostics in the care of advanced cancer patients highlights the desire for improved access to tumor allowing accurate tumor genotyping (1). Genotyping of plasma cfDNA is now routine for detection of EGFR driver mutations at diagnosis of NSCLC, or for detection of the EGFR T790M mutation after TKI resistance, and is an emerging approach for the detection of other drivers (HER2 or BRAF mutations, ALK or ROS1 fusions…) (2) or the estimation of tumor mutation burden (TMB) (3). However, the most sensitive plasma genotyping platforms still have a sensitivity of only 70%-80%, such that a negative result requires tissue biopsy confirmation.
Read the detailed description
The wide uptake of "liquid biopsy" diagnostics in the care of advanced cancer patients highlights the desire for improved access to tumor allowing accurate tumor genotyping (1). Genotyping of plasma cfDNA is now routine for detection of EGFR driver mutations at diagnosis of NSCLC, or for detection of the EGFR T790M mutation after TKI resistance, and is an emerging approach for the detection of other drivers (HER2 or BRAF mutations, ALK or ROS1 fusions…) (2) or the estimation of tumor mutation burden (TMB) (3). However, the most sensitive plasma genotyping platforms still have a sensitivity of only 70%-80%, such that a negative result requires tissue biopsy confirmation. This poses a clinical challenge because negative plasma genotyping is correlated with more limited metastatic spread and lower tumor burden, such that biopsy of these patients may be even more challenging. Because invasive biopsy remains an integral part of the diagnostic strategy, methods are needed for maximizing the yield from these biopsy procedures.
There is a current paradox between the need for large amounts of tissue for multiplex analysis of an increasing number of targetable drivers and markers of response to immune therapy (PD-L1, TMB) and the development of minimally invasive biopsy procedures that results in limited specimens. Up to 25% of patients are thus treated without knowledge of the molecular profile of their tumor (4). In particular, 20% of endobronchial ultrasonography transbronchial needle aspiration (EBUS-TBNA) are rejected from genotyping due to lack of tissue (5) after time and tissue consuming diagnostics steps that are sometimes not required (resistance setting). Circulating tumor DNA is an emerging approach for cancer genotyping but sensitivity is limited to 70-80% (6) by inconsistent tumor shed and low DNA concentrations, so that tissue biopsy is still routine. Also, feasibility of TMB assessment on tissue is only 60% (likely much less on EBUS-TBNA specimens) (7) and approximately 80% in plasma (blood TMB, bTMB) (3).
The presence of cfDNA in several biological fluids and the feasibility of detecting mutations of interest (usually targeting only EGFR) in these fluids (urine, pleural fluid, CSF) have been clearly demonstrated (8-12), while blood is the most widely studied liquid biopsy substrate in advanced NSCLC.
Furthermore, we showed in a proof of concept study, investigating various FNA specimens in a limited numbers of patients that cytology samples' supernatant (usually discarded) is a rich source of DNA. Our results suggest that supernatant free DNA (sfDNA) can be used for baseline and resistance genotyping (13).
- Conditions
- Lung Cancer
- Being tested
- Molecular analysis of surnatant
- Keywords
- NSCLC, genotyping, liquid biopsy, cytology supernatant
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Molecular analysis of surnatantOther
The interventional pulmonologist selects the most suspect node. The corresponding TBNA is placed in Cytolyt and tagged using a sticker to indicate the specimen from which supernatant must be saved after the initial spin.
The supernatant is transferred to the "Laboratoire de Biologie Médicale Oncologique" where it undergoes a further hard spin. The remaining supernatant is stored at -80°C before to send it to Foundation One for DNA extraction from 3 ml of supernatant and genotyping.
Two 7,5 mL blood tubes are transferred to the laboratory to extract plasma. Plasma was stored at -80°C and then sent to Foundation One for DNA extraction from 2 mL of plasma and genotyping.
10 slides from the cell block are shipped to Foundation One. These specimens are tested by FoundationOne®CDX (tissue), and FoundationOne®Liquid (supernatant and plasma) for genomic and TMB analyses (hybrid-capture based next generation sequencing).
| Study group | Role | What they receive |
|---|---|---|
| Identified mutation | The sensitivity of supernatant to identify the mutations detected on cell block (Gold standard). Receives: Other: Molecular analysis of surnatant | |
| Non identified mutation | The sensitivity of supernatant to identify the mutations detected on cell block (Gold standard). Receives: Other: Molecular analysis of surnatant |
What is being measured
The primary outcome is the main question the study is designed to answer.
main aim of the study
to investigate the sensitivity of sfDNA genotyping in various clinical settings and to compare it to cell block
Measured: 18 months
Secondary outcomes (6)
TMB estimation
To assess the feasibility of TMB estimation on this specimen
Measured: 18 months
sensitivity of plasma
To compare the sensitivity of plasma genotyping to cell block
Measured: 18 months
concordance between plasma and supernatant
To investigate the concordance between plasma and supernatant for mutation detection and TMB estimation
Measured: 18 months
mutation rate
To calculate the rate of patients with at least one additional mutation detected on supernatant compared to cell block
Measured: 18 months
Sensitivity of supernatant and plasma
To compare the sensitivity of supernatant and plasma to cell block for the detection of specific alterations (EGFR, HER2, BRAF, PIK3CA, KRAS, MET mutations, ALK, ROS1, NTRK, RET fusions)
Measured: 18 months
Turnaround time of supernatant
To compare the turnaround time of supernatant, plasma and cell block for genotyping
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2020
- Study start1 Apr 2021
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicolas Guibert, Principal investigator, University Hospital, Toulouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04624373
- Sponsor's protocol ID
- RC31/19/0090
- Acronym
- CELTICS
- Status last verified
- Mar 2025
- First submitted
- 9 Nov 2020
- Last updated
- 3 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Analysis of the Surnantant of Echoguidated Bronchoscopic Cytopunctions in Lung Cancer
- ClinicalTrials.gov ID
- NCT04624373
- Acronym / sponsor ID
- CELTICS / RC31/19/0090
- Conditions
- Lung Cancer
- Keywords
- NSCLC, genotyping, liquid biopsy, cytology supernatant
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 10 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The wide uptake of "liquid biopsy" diagnostics in the care of advanced cancer patients highlights the desire for improved access to tumor allowing accurate tumor genotyping (1). Genotyping of plasma cfDNA is now routine for detection of EGFR driver mutations at diagnosis of NSCLC, or for detection of the EGFR T790M mutation after TKI resistance, and is an emerging approach for the detection of other drivers (HER2 or BRAF mutations, ALK or ROS1 fusions…) (2) or the estimation of tumor mutation burden (TMB) (3). However, the most sensitive plasma genotyping platforms still have a sensitivity of only 70%-80%, such that a negative result requires tissue biopsy confirmation.
Detailed description
The wide uptake of "liquid biopsy" diagnostics in the care of advanced cancer patients highlights the desire for improved access to tumor allowing accurate tumor genotyping (1). Genotyping of plasma cfDNA is now routine for detection of EGFR driver mutations at diagnosis of NSCLC, or for detection of the EGFR T790M mutation after TKI resistance, and is an emerging approach for the detection of other drivers (HER2 or BRAF mutations, ALK or ROS1 fusions…) (2) or the estimation of tumor mutation burden (TMB) (3). However, the most sensitive plasma genotyping platforms still have a sensitivity of only 70%-80%, such that a negative result requires tissue biopsy confirmation. This poses a clinical challenge because negative plasma genotyping is correlated with more limited metastatic spread and lower tumor burden, such that biopsy of these patients may be even more challenging. Because invasive biopsy remains an integral part of the diagnostic strategy, methods are needed for maximizing the yield from these biopsy procedures.
There is a current paradox between the need for large amounts of tissue for multiplex analysis of an increasing number of targetable drivers and markers of response to immune therapy (PD-L1, TMB) and the development of minimally invasive biopsy procedures that results in limited specimens. Up to 25% of patients are thus treated without knowledge of the molecular profile of their tumor (4). In particular, 20% of endobronchial ultrasonography transbronchial needle aspiration (EBUS-TBNA) are rejected from genotyping due to lack of tissue (5) after time and tissue consuming diagnostics steps that are sometimes not required (resistance setting). Circulating tumor DNA is an emerging approach for cancer genotyping but sensitivity is limited to 70-80% (6) by inconsistent tumor shed and low DNA concentrations, so that tissue biopsy is still routine. Also, feasibility of TMB assessment on tissue is only 60% (likely much less on EBUS-TBNA specimens) (7) and approximately 80% in plasma (blood TMB, bTMB) (3).
The presence of cfDNA in several biological fluids and the feasibility of detecting mutations of interest (usually targeting only EGFR) in these fluids (urine, pleural fluid, CSF) have been clearly demonstrated (8-12), while blood is the most widely studied liquid biopsy substrate in advanced NSCLC.
Furthermore, we showed in a proof of concept study, investigating various FNA specimens in a limited numbers of patients that cytology samples' supernatant (usually discarded) is a rich source of DNA. Our results suggest that supernatant free DNA (sfDNA) can be used for baseline and resistance genotyping (13).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Identified mutation | – | Other: Molecular analysis of surnatantThe sensitivity of supernatant to identify the mutations detected on cell block (Gold standard). |
| Non identified mutation | – | Other: Molecular analysis of surnatantThe sensitivity of supernatant to identify the mutations detected on cell block (Gold standard). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients will be recruited in our Department in Toulouse University Hospital, during appointment needed for information and planning of the EBUS-TBNA procedure.
Key inclusion criteria (6 listed)
- Age > 18 years-old
- Patients planned for an EBUS-TBNA for
- Performance status 0-3
- Informed consent
Key exclusion criteria (2 listed)
- Refusal to participate
- Patient under legal tutelage
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Molecular analysis of surnatantThe interventional pulmonologist selects the most suspect node. The corresponding TBNA is placed in Cytolyt and tagged using a sticker to indicate the specimen from which supernatant must be saved after the initial spin. The supernatant is transferred to the "Laboratoire de Biologie Médicale Oncologique" where it undergoes a further hard spin. The remaining supernatant is stored at -80°C before to send it to Foundation One for DNA extraction from 3 ml of supernatant and genotyping. Two 7,5 mL blood tubes are transferred to the laboratory to extract plasma. Plasma was stored at -80°C and then sent to Foundation One for DNA extraction from 2 mL of plasma and genotyping. 10 slides from the cell block are shipped to Foundation One. These specimens are tested by FoundationOne®CDX (tissue), and FoundationOne®Liquid (supernatant and plasma) for genomic and TMB analyses (hybrid-capture based next generation sequencing). | Other | Identified mutation, Non identified mutation |
Primary outcome
main aim of the study
Time frame: 18 months
to investigate the sensitivity of sfDNA genotyping in various clinical settings and to compare it to cell block
6 secondary outcomes
TMB estimation
Time frame: 18 months
sensitivity of plasma
Time frame: 18 months
concordance between plasma and supernatant
Time frame: 18 months
mutation rate
Time frame: 18 months
Sensitivity of supernatant and plasma
Time frame: 18 months
Turnaround time of supernatant
Time frame: 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2025.
Related trials for Lung Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nicolas Guibert principal investigator
University Hospital, Toulouse
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lung Cancer, run by University Hospital, Toulouse at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nicolas Guibert, MD (567778160 ext. +33, guibert.n@chu-toulouse.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
main aim of the study (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2025.