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Metastatic Lung CancerLIBELULENCT03721120

Evaluation of the Feasibility and Clinical Relevance of Liquid Biopsy in Patients With Suspicious Metastatic Lung Cancer

A study testing InvisionFirst® molecular panel in people with Metastatic Lung Cancer, run by Centre Leon Berard at 16 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Lung cancer is diagnosed at metastatic stage in 60% of the cases. For these patients, first-line treatment is based on histology and molecular characterization of non-squamous non-small cell lung cancer (NSCLC). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Lung Cancer
What is being tested?
InvisionFirst® molecular panel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
319 participants
Where
16 sitesFrance
Study dates
10 Apr 2019to 1 Jul 2023
Phase
Interventional
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥ 18 years;
  • Patients with clinico-radiological suspicious presentation of stage IV lung cancer;
  • No prior chemotherapy for locally advanced or metastatic NSCLC;
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 (Appendix 2);
  • Life expectancy > 12 weeks;
  • No contraindication to systemic lung cancer treatment;
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  • Covered by a medical insurance;
  • Signed informed consent prior to any study-specific procedure;
  • No prior biopsy or cytology for lung cancer diagnosis.

Who cannot join

  • Pregnant or breastfeeding women;
  • Patient concurrently using other approved or investigational antineoplastic agents;
  • Major concurrent disease affecting cardiovascular system, liver, kidneys, hematopoietic system or else considered as clinically important by the investigator and that could be incompatible with patient's participation in this trial or would likely interfere with study procedures or results;
  • Prior history of malignancies other than study disease (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the patient has been free of the disease for at least 3 years;
  • Patient requiring tutorship or curatorship.

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

France16 sites
  • Centre Hospitalier de Bayeux

    Bayeux, 14400

  • Hopital Louis Pradel

    Bron, 69677

  • Centre François Baclesse

    Caen, 14000

  • Centre Maurice Tubiana

    Caen, 14000

  • Infirmerie Protestante

    Caluire-et-Cuire, 69641

  • Centre Hospitalier Public du Cotentin

    Cherbourg, 50100

  • CH Les Oudairies

    La Roche-sur-Yon, 85925

  • Hôpital Privé Jean Mermoz

    Lyon, 69008

  • Centre Leon Berard

    Lyon, 69373

  • Groupe Hospitalier de la région de Mulhouse et Sud-Alsace

    Mulhouse, 68051

  • Centre Hospitalier Annecy Genevois

    Pringy, 74374

  • CHRU Saint-Etienne

    Saint-Etienne, 42277

  • Institut de Cancérologie Lucien Neuwirth

    Saint-Priest-en-Jarez, 42271

  • Centre Paul Strauss

    Strasbourg, 67065

  • Hôpital Nord-Ouest

    Villefranche-sur-Saône, 69655

  • Médiôle Lyon-Villeurbanne

    Villeurbanne, 69100

Other trials in France

About this study

Official title: A Randomized Phase III Clinical Trial to Evaluate the Feasibility and Clinical Relevance of Liquid Biopsy in Patients With Suspicious Metastatic Lung Cancer

Lung cancer is diagnosed at metastatic stage in 60% of the cases. For these patients, first-line treatment is based on histology and molecular characterization of non-squamous non-small cell lung cancer (NSCLC). Thus, quality and quantity of tumor tissue are crucial to determine the appropriate treatment (targeted therapies, chemotherapy and immunotherapy).

However, in routine practice, tissue quality and quantity can be limited (25%), resulting in the need for tumor rebiopsy for molecular analysis. Therefore, lung cancer patients often experience substantial delays before treatment initiation that may be associated with worse patient experience of subsequent cancer care and poorer clinical outcomes.

Read more

"Liquid biopsies" (LB) are used to detect genomic alterations in cell-free circulating DNA (cfDNA). Since very recently, they are routinely used in reference centers for the detection of EGFR-mutations when tissue is not sufficient for molecular characterization. Importantly, the feasibility and clinical relevance of systematic liquid biopsies in routine practice has never been evaluated in patients with suspicious advanced lung cancer.

Investigators hypothesize that using systematic LB in patients with clinical suspicion of metastatic lung cancer may reduce time-to-treatment initiation and avoid tissue rebiopsy.

Investigators performed a retrospective study including 250 NSCLC patients treated in a tertiary Cancer Center and in the University Hospital of Lyon, France. The mean time-to-appropriate frontline treatment initiation (TTI) was 42+/-22.5 days. With the use of LB at the time of first consultation, the investigators believe it is possible to reduce the mean TTI down to 33 days (21% reduction in TTI) in the overall population with suspicious metastatic lung cancer, including a 50% and 40% reduction in TTI for EGFR/ALK/ROS1/BRAF V600E subgroups and KRAS/LKB1/ERBB2/c-MET/BRAF non V600E subgroups, respectively.

Investigators therefore designed a "real-life" randomized study to evaluate the feasibility and clinical relevance of LB to decrease the TTI, which may in turn improve patients' outcome. Genomic analyses of circulating cfDNA will be performed using a robust and highly sensitive technology (InVision®), that profiles the presence of genomic aberrations in a panel of 35 genes including mutations, insertion/deletions and rearrangements, including all actionable alterations required to initiate the appropriate first-line therapy (EGFR-, ALK-, ROS1 and BRAF V600E).

Being tested
InvisionFirst® molecular panel
Medical subject headings
Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • InvisionFirst® molecular panelDiagnostic test

    During the first visit, liquid biopsy will be performed using the InVisionFirst® panel. Cytological or histological sampling will be planned. According to InVisionFirst® results, treatment will be initiated:

    • regardless of cytological/histological and tissue molecular analysis in case of EGFR, BRAF V600E-mutation, ALK- or ROS1-rearrangement identified on InvisionFirst® panel.
    • regardless of molecular characterization performed on tissue sample in case of ERBB2-, BRAF non V600E-, c-MET-, KRAS-,LKB1-, NTRK and/or RET mutation on InVisionFirst® panel. Treatment will be based on pathology results and if appropriate on PD-L1 level of expression.
    • for patients with none of the previous alterations, treatment will be initiated after obtaining pathology results and genomic characterization from the tumor tissue analysis.
Study groups in NCT03721120
Study groupRoleWhat they receive
Liquid biopsyExperimentalLiquid biopsy will be performed at the first visit using InVisionFirst®. Treatment will be determined by (i) genomic characterization in plasma for patients with druggable alteration in first-line, (ii) after pathology results (including assessment of PD-L1 level of expression by immunohistochemistry) for patients with an informative molecular characterization on plasma and no druggable alteration in first-line and (iii) after pathology results and tissue molecular characterization for the remaining patients.
Receives: Diagnostic Test: InvisionFirst® molecular panel
Cytological or histological samplingNo interventionDuring the first visit, cytological or histological sampling will be planned and treatment will be initiated according to European Society of Medical Oncology (ESMO) recommendations; in case of a tissue sample inadequate for genomic characterization, physicians may resort to liquid biopsy according to their usual practice and available technology.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time-to-appropriate Treatment Initiation (TTI)

    It is defined as the time between the date of randomization and the date of appropriate-treatment initiation (whatever the start date occurs before or after the biopsy results). As all the patients will receive an appropriate-treatment, no censored data are expected, thus the TTI will be analyzed as a continuous outcome. Appropriate treatment is defined as follow:

    • Based on contributive results on tissue OR liquid biopsy:
    • EGFR- or BRAF V600E-mutations, ALK- or ROS1- rearrangements: specific targeted therapies
    • None of the four previous alterations: investigator's choice (chemotherapy and/or immunotherapy or targeted therapies based on pathology results, PD-L1 expression and access to therapies in the context of Temporary Used Authorization or clinical trials)
    • In case of non-contributive results on tissue AND liquid biopsy: any treatment initiated by investigator (chemotherapy or immunotherapy based on pathology results and PD-L1 level of expression).

    Measured: From date of randomisation to start date of appropriate treatment , assessed up to 12 months

Secondary outcomes (15)
  1. Rate of treatment initiated before molecular results

    Defined as the proportion of patients with a treatment initiated without any available molecular results (tissue and liquid biopsy)

    Measured: From date of randomisation to 12 months

  2. Time to availability of informative molecular pathology results

    Defined as the time from randomization to date of availability of informative molecular pathology results (positive or negative).

    Measured: From date of randomisation to date of molecular results, assessed up to 12 months

  3. Progression Free Survival (PFS)

    Defined as the time from randomization to the date of the first documented clinical or radiological progression (as per RECIST version 1.1.) or death due to any cause.Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment.

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 30 months

  4. Incidence of diagnostic test-emergent adverse events

    Safety assessed according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version5

    Measured: From date of randomization to follow-up visit month 12 or death due to any cause, whichever came first, assessed up to 30 months

  5. The impact of cancer on the patient's quality of life using the European Organisation for Research and Treatment of Cancer (EORTC) quality-of-life core questionnaire (QLQ-C30)

    64 questions related to cancer impact on health and daily activities composed this questionnaire. Each item has to be graded from 1 to 4 (1 = not at all, 4= very much). More the score is high, worst the quality of life is.

    Measured: At baseline, at Day 21 post-baseline, at the time of treatment initiation (within 6 weeks after baseline), at 8 weeks post treatment initiation and every 3 months post initiation of treatment until 12 months

  6. Evaluation of lung cancer symptoms impact on health and daily activities using the Lung Cancer Symptoms Scale (LCSS) questionnaire

    10 questions related to lung cancer symptoms impact on health and daily activities composed this questionnaire. Each item has to be graded from 1 to 10. More the score is high, worst the quality of life is.

    Measured: At baseline, at Day 21 post-baseline, at the time of treatment initiation (within 6 weeks after baseline), at 8 weeks post treatment initiation and every 3 months post initiation of treatment until 12 months

  7. Evaluation of anxiety and depression level using Hospital Anxiety and Depression (HAD)Scale

    6 questions related to anxiety and 6 questions related to depression composed this questionnaire. Each item has to be graded from 0 to 3. More the score of anxiety or depression is high, worst the quality of life is.

    Measured: At baseline, at Day 21 post-baseline, at the time of treatment initiation (within 6 weeks after baseline), and at 8 weeks post treatment initiation

  8. Concordance between molecular status on tissue and liquid biopsies in the experimental arm

    Evaluated by the proportion of discordances (error rates) between tissue and liquid biopsies for the mutational status.

    Measured: From date of randomization to follow-up visit month 12 or death due to any cause, whichever came first, assessed up to 30 months

  9. Biopsy avoidance rate in the experimental arm

    Be defined as the proportion of patients with an initial non-informative tissue biopsy and an informative liquid biopsy allowing appropriate treatment initiation without need for tissue rebiopsy.

    Measured: From date of randomization to follow-up visit month 12 or death due to any cause, whichever came first, assessed up to 30 months

  10. The cost analysis

    All costs items related to the stratégies and supported by the payers will be collected prospectively for each patient. Mean total costs will be calculated for the 2 stratégies and be compared between the arms.

    Measured: From date of randomization to follow-up visit month 12 or death due to any cause, whichever came first, assessed up to 30 months

  11. The effectiveness analysis using the EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L)

    Preferences will be measured using EuroQoL 5 Dimensions 5 Levels questionnaire. Five attributes will therefore be investigated: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. Each attributes having five levels (from "able to […]"/"no pain/discomfort/anxiety/depression" to "unable to […]"/ "extremely pain/discomfort/anxiety/depression"). More the patient is unable to doing daily activities and painful/anxious, worst the quality-adjusted life-year (QALYs) is.

    Measured: At baseline, at Day 21 post-baseline, at the time of treatment initiation (within 6 weeks after baseline), at 8 weeks post treatment initiation and every 3 months post initiation of treatment until 12 months

  12. QALYS comparaison between 2 arms

    Mean QALYs (based on EQ-5D-5L score) will be calculated for each arm and will be compared between the 2 arms.

    Measured: At baseline, at Day 21 post-baseline, at the time of treatment initiation (within 6 weeks after baseline), at 8 weeks post treatment initiation and every 3 months post initiation of treatment until 12 months

  13. The budget impact analysis in experimental arm

    The Liquid biopsy using the InVisionFirst® cost, the evolution of market shares, the data pertaining to the target population, and the costs involved with treating the pathologies will be analysed to to estimate the budget impact on the French National Health Insurance of the generalization of innovative Liquid biopsy using the InVisionFirst® panel strategy.

    Measured: From date of randomization to follow-up visit month 12 or death due to any cause, whichever came first, assessed up to 30 months

  14. Exploratory objectives : Whole-exome sequencing

    Additional mandatory 10 ml DNA STRECK tubes will be collected for patients signing study consent.

    Measured: At baseline, at the time of treatment initiation (within 6 weeks after baseline), at 8 weeks after the treatment initiation, and at the progression if occured within 12 month post-baseline.

  15. Exploratory objectives : miRNA profiling

    Additional mandatory 10 ml RNA STRECK tubes will be collected for patients signing study consent.

    Measured: At baseline, at the time of treatment initiation (within 6 weeks after baseline), at 8 weeks after the treatment initiation, and at the progression if occured within 12 month post-baseline.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Oct 2018
  2. Study start10 Apr 2019
  3. Primary completion1 Jul 2023
  4. Study completion1 Jul 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Diagnosis
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
319 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03721120
Sponsor's protocol ID
ET18-086 LIBELULE
Acronym
LIBELULE
Status last verified
Aug 2025
First submitted
17 Oct 2018
Last updated
8 Aug 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Swalduz A, Schiffler C, Curcio H, Ambasager B, Le Moel G, Debieuvre D, Dot JM, Duruisseaux M, Fournel P, Odier L, Demolombe S, Bizieux-Thaminy A, Peytier A, Schott R, Hominal S, Tissot C, Bombaron P, Metzger S, Donnat M, Ortiz-Cuaran S, Rosenfeld N, Pipinikas C, Saintigny P, Perol M. LIBELULE: A Randomized Phase III Study to Evaluate the Clinical Relevance of Early Liquid Biopsy in Patients With Suspicious Metastatic Lung Cancer. J Thorac Oncol. 2025 Apr;20(4):437-450. doi: 10.1016/j.jtho.2024.12.011. Epub 2024 Dec 16.

    PubMed 39694415

Questions about this trial

What is this clinical trial studying?

A study testing InvisionFirst® molecular panel in people with Metastatic Lung Cancer, run by Centre Leon Berard at 16 sites 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 9 inclusion and 5 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: finished, as of the sponsor's last update on 8 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time-to-appropriate Treatment Initiation (TTI) (time frame: From date of randomisation to start date of appropriate treatment , assessed up to 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03721120, which also lists 1 linked publication.

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 8 Aug 2025.

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