Clinical trial NCT03721120: Evaluation of the Feasibility and Clinical Relevance of Liquid Biopsy in Patients With Suspicious Metastatic Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metastatic Lung Cancer
Lead sponsor: Centre Leon Berard
Sponsor class: OTHER
First posted: 2018-10-26
Enrollment: 319
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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).


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Time-to-appropriate Treatment Initiation (TTI)
timeFrame: From date of randomisation to start date of appropriate treatment , assessed up to 12 months
Secondary outcomes:
measure: Rate of treatment initiated before molecular results
timeFrame: From date of randomisation to 12 months
measure: Time to availability of informative molecular pathology results
timeFrame: From date of randomisation to date of molecular results, assessed up to 12 months
measure: Progression Free Survival (PFS)
timeFrame: 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
measure: Incidence of diagnostic test-emergent adverse events
timeFrame: From date of randomization to follow-up visit month 12 or death due to any cause, whichever came first, assessed up to 30 months
measure: 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)
timeFrame: 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
measure: Evaluation of lung cancer symptoms impact on health and daily activities using the Lung Cancer Symptoms Scale (LCSS) questionnaire
timeFrame: 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
measure: Evaluation of anxiety and depression level using Hospital Anxiety and Depression (HAD)Scale
timeFrame: 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
measure: Concordance between molecular status on tissue and liquid biopsies in the experimental arm
timeFrame: From date of randomization to follow-up visit month 12 or death due to any cause, whichever came first, assessed up to 30 months
measure: Biopsy avoidance rate in the experimental arm
timeFrame: From date of randomization to follow-up visit month 12 or death due to any cause, whichever came first, assessed up to 30 months
measure: The cost analysis
timeFrame: From date of randomization to follow-up visit month 12 or death due to any cause, whichever came first, assessed up to 30 months
measure: The effectiveness analysis using the EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L)
timeFrame: 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
measure: QALYS comparaison between 2 arms
timeFrame: 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
measure: The budget impact analysis in experimental arm
timeFrame: From date of randomization to follow-up visit month 12 or death due to any cause, whichever came first, assessed up to 30 months
measure: Exploratory objectives : Whole-exome sequencing
timeFrame: 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.
measure: Exploratory objectives : miRNA profiling
timeFrame: 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.
Other outcomes:
Locations:
city: Bayeux
country: France
facility: Centre Hospitalier de Bayeux
city: Bron
country: France
facility: Hopital Louis Pradel
city: Caen
country: France
facility: Centre François Baclesse
city: Caen
country: France
facility: Centre Maurice Tubiana
city: Caluire et Cuire
country: France
facility: Infirmerie Protestante
city: Cherbourg
country: France
facility: Centre Hospitalier Public du Cotentin
city: La Roche-sur-Yon
country: France
facility: CH Les Oudairies
city: Lyon
country: France
facility: Hôpital Privé Jean Mermoz
city: Lyon
country: France
facility: Centre Leon Berard
city: Mulhouse
country: France
facility: Groupe Hospitalier de la région de Mulhouse et Sud-Alsace
city: Pringy
country: France
facility: Centre Hospitalier Annecy Genevois
city: Saint-Priest-en-Jarez
country: France
facility: Institut de Cancérologie Lucien Neuwirth
city: Saint-Étienne
country: France
facility: CHRU Saint-Etienne
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Villefranche-sur-Saône
country: France
facility: Hôpital Nord-Ouest
city: Villeurbanne
country: France
facility: Médiôle Lyon-Villeurbanne
Study officials:
References: