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

NCT03721120 | Completed

• 1 other identifier: ET18-086 LIBELULE
• Study Type: interventional
• Target: 319
• Locations: 1 country
• Sites: 16

Brief 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). 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. "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).

Conditions

Metastatic Lung Cancer

Outcome Measures

Primary Outcomes (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).

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

Secondary Outcomes (15)

• Rate of treatment initiated before molecular results

  From date of randomisation to 12 months

• Time to availability of informative molecular pathology results

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

• Progression Free Survival (PFS)

  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

• Incidence of diagnostic test-emergent adverse events

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

• 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)

  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

Study Arms (2)

Liquid biopsy

EXPERIMENTAL

Liquid 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.

Diagnostic Test: InvisionFirst® molecular panel

Cytological or histological sampling

NO INTERVENTION

During 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.

Interventions

InvisionFirst® molecular panel DIAGNOSTIC_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.

Liquid biopsy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Covered by a medical insurance;
• Signed informed consent prior to any study-specific procedure;
• No prior biopsy or cytology for lung cancer diagnosis.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (16)

Centre Hospitalier de Bayeux

Bayeux, 14400, France

Location

Hopital Louis Pradel

Bron, 69677, France

Location

Centre François Baclesse

Caen, 14000, France

Location

Centre Maurice Tubiana

Caen, 14000, France

Location

Infirmerie Protestante

Caluire-et-Cuire, 69641, France

Location

Centre Hospitalier Public du Cotentin

Cherbourg, 50100, France

Location

CH Les Oudairies

La Roche-sur-Yon, 85925, France

Location

Hôpital Privé Jean Mermoz

Lyon, 69008, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Groupe Hospitalier de la région de Mulhouse et Sud-Alsace

Mulhouse, 68051, France

Location

Centre Hospitalier Annecy Genevois

Pringy, 74374, France

Location

CHRU Saint-Etienne

Saint-Etienne, 42277, France

Location

Institut de Cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, 42271, France

Location

Centre Paul Strauss

Strasbourg, 67065, France

Location

Hôpital Nord-Ouest

Villefranche-sur-Saône, 69655, France

Location

Médiôle Lyon-Villeurbanne

Villeurbanne, 69100, France

Location

MeSH Terms

Conditions

Lung Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2018
• First Posted: October 26, 2018
• Study Start: April 10, 2019
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2023
• Last Updated: August 8, 2025

Record last verified: 2025-08

Locations

FR (16)