Clinical trial NCT04677205: Molecular Signature From Tumor to Lymph Nodes
Official title: Molecular Signature From Tumor to Lymph Nodes: How to Identify the Right Candidate for IIIA-N2 Lung Cancer Surgery?
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Lung Cancer
Stage IIIA-cN2
Operated With Curative Intent
Primary Tumor Tissue Available
Node Tumor Tissue Available
Keywords: NSCLC
N2
molecular profile
prognosis
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: National Cancer Institute, France
name: Ministry of Health, France
name: Université de Paris
First posted: 2020-12-21
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 230 patients in 11 French centers in order to have 200 eligible patients. Objectives are 120 patients recruited retrospectively and 110 prospectively.

Inclusion criteria are: all consecutive patients operated with a curative intent for an IIIA-cN2 NSCLC.

Brief summary: Mediastinal lymph node (LN) involvement (N2) in non-small cell lung cancer (NSCLC) concerns 15% of resectable tumors and is associated with a poor prognosis and an overall survival reaching 9 to 49%. Literature fails to provide any definitive consensus regarding the management of these patients, except for the platinum-based doublet chemotherapy. The N2 involvement remains a matter of debate because of its not yet well-classified heterogeneity. Regarding anatomy, the Mountain and Dresler's regional LN classification for lung cancer staging remains the reference. Different studies classified IIIA-N2 disease into 4 groups, in addition to the skip-N2 phenomenon: minimal-N2, N2 single station, N2 multiple stations, and bulky-N2. Other subgroups were recently proposed for the 8th edition of the TNM: N2a1 - single station skip, N2a2 - single station non-skip, N2b - multiple stations.

The French National Cancer Institute (INCa) proposed guidelines, but in case of cN2 staging without mediastinal infiltration, guidelines remained imprecise ("resectability should be discussed for each case") and suggested surgery first, or induction chemotherapy, or concomitant chemoradiation.

Thus, optimal management of cIIIA-N2 remains controversial but complete tumor resection can be related to long-term survival in some patients, including 10 years after surgery \[1\]. In this situation, the identification of markers that will help select IIIA-N2 patients who will benefit from surgical resection is mandatory.

Detailed description: We planned a comprehensive molecular characterization of tumors and lymph nodes to evaluate the impact of molecular signatures and molecular heterogeneity on disease-free survival after surgery in IIIA-N2 NSCLC patients. Identification of specific molecular profiles in primary tumors and evolution profiles in nodes might provide clues to the potential risk of metastatic evolution and trigger specific management.

For patients included prospectively, we planned to analyze cell free circulating tumor DNA (ctDNA) as prognostic marker. Because multiple biopsies are not always available in care settings, ctDNA could also be analyzed as a surrogate marker of molecular heterogeneity. Next generation sequencing (NGS) that was validated in our lab to screen ctDNA using a specific bio-informatics workflow allows accurate and cost effective ctDNA screening

Eligibility criteria: Inclusion Criteria:

* Adult patient, men and women age \>18 years
* Patients operated with a curative intent for an IIIA-cN2 NSCLC
* Social security affiliation
* Written informed consent for patient included in part 2 (prospective) or not opposing the use of this data for patient included in part 1 (retrospective)

Exclusion Criteria:

* Patient with T4, R1 or R2 surgical resection, sublobar resection, no radical lymphadenectomy
* Patient under protectives measures
* Pregnancy or breast-feeding

Primary outcomes:
measure: 3-year disease-free survival
timeFrame: 3 years
Secondary outcomes:
measure: 5-year disease-free survival
timeFrame: 5 years
measure: pathological architectural patterns WHO 2015 classification
timeFrame: 5 years
measure: anatomical lymphatic spread
timeFrame: at the end of molecular analyses
measure: ctDNA
timeFrame: 3 years
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Hôpital du Haut-Lévêque, CHU de Bordeaux
city: Clamart
country: France
facility: Hôpital Militaire Percy
city: Marseille
country: France
facility: Hôpital Nord
city: Nice
country: France
facility: Hôpital Pasteur, CHU de Nice
city: Paris
country: France
facility: Hegp-Aphp
city: Paris
country: France
facility: Hôpital Européen Georges-Pompidou
city: Paris
country: France
facility: Hôpital Bichat
city: Paris
country: France
facility: Hôpital Cochin
city: Rennes
country: France
facility: Hôpital Pontchaillou, CHU de Rennes
city: Strasbourg
country: France
facility: Hôpitaux universitaires de Strasbourg
city: Toulouse
country: France
facility: Hôpital Larrey, CHU de Toulouse
city: Tours
country: France
facility: CHRU de Tours
Study officials:
affiliation: Hôpital Européen Georges-Pompidou
name: Helene BLONS, PharmD PhD
role: PRINCIPAL_INVESTIGATOR
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