Molecular Signature From Tumor to Lymph Nodes

Lung Cancer Clinical Trial

— N2-3S  

Official title:

Molecular Signature From Tumor to Lymph Nodes: How to Identify the Right Candidate for IIIA-N2 Lung Cancer Surgery?

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04677205
• Other study ID #: D20180155
• Secondary ID: D201801552019-A0
• Status: Recruiting
• Start date: March 30, 2021
• Est. completion date: November 2027

Study information

• Verified date: January 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Antoine LEGRAS, MD PhD
• Phone: 33 2 47474747
• Email: antlegras[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: November 2027
• Est. primary completion date: November 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms
• Neoplasms
• Node Tumor Tissue Available
• Operated With Curative Intent
• Primary Tumor Tissue Available
• Stage IIIA-cN2

Locations

Country	Name	City	State
France	Hôpital du Haut-Lévêque, CHU de Bordeaux	Bordeaux
France	Hôpital Militaire Percy	Clamart
France	Hôpital Nord	Marseille
France	Hôpital Pasteur, CHU de Nice	Nice
France	Hegp-Aphp	Paris
France	Hôpital Bichat	Paris
France	Hôpital Cochin	Paris
France	Hôpital Européen Georges-Pompidou	Paris
France	Hôpital Pontchaillou, CHU de Rennes	Rennes
France	Hôpitaux universitaires de Strasbourg	Strasbourg
France	Hôpital Larrey, CHU de Toulouse	Toulouse
France	CHRU de Tours	Tours

Sponsors (4)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Ministry of Health, France, National Cancer Institute, France, Université de Paris

Country where clinical trial is conducted

France, 

References & Publications (8)

Altman DG, McShane LM, Sauerbrei W, Taube SE. Reporting recommendations for tumor marker prognostic studies (REMARK): explanation and elaboration. BMC Med. 2012 May 29;10:51. doi: 10.1186/1741-7015-10-51. — View Citation

Legras A, Mordant P, Arame A, Foucault C, Dujon A, Le Pimpec Barthes F, Riquet M. Long-term survival of patients with pN2 lung cancer according to the pattern of lymphatic spread. Ann Thorac Surg. 2014 Apr;97(4):1156-62. doi: 10.1016/j.athoracsur.2013.12.047. Epub 2014 Feb 26. — View Citation

Lin IF, Chang WP, Liao YN. Shrinkage methods enhanced the accuracy of parameter estimation using Cox models with small number of events. J Clin Epidemiol. 2013 Jul;66(7):743-51. doi: 10.1016/j.jclinepi.2013.02.002. Epub 2013 Apr 6. — View Citation

Pecuchet N, Rozenholc Y, Zonta E, Pietrasz D, Didelot A, Combe P, Gibault L, Bachet JB, Taly V, Fabre E, Blons H, Laurent-Puig P. Analysis of Base-Position Error Rate of Next-Generation Sequencing to Detect Tumor Mutations in Circulating DNA. Clin Chem. 2016 Nov;62(11):1492-1503. doi: 10.1373/clinchem.2016.258236. Epub 2016 Sep 13. — View Citation

Peduzzi P, Concato J, Feinstein AR, Holford TR. Importance of events per independent variable in proportional hazards regression analysis. II. Accuracy and precision of regression estimates. J Clin Epidemiol. 1995 Dec;48(12):1503-10. doi: 10.1016/0895-4356(95)00048-8. — View Citation

Tapak L, Saidijam M, Sadeghifar M, Poorolajal J, Mahjub H. Competing risks data analysis with high-dimensional covariates: an application in bladder cancer. Genomics Proteomics Bioinformatics. 2015 Jun;13(3):169-76. doi: 10.1016/j.gpb.2015.04.001. Epub 2015 Apr 20. — View Citation

Um SW, Joung JG, Lee H, Kim H, Kim KT, Park J, Hayes DN, Park WY. Molecular Evolution Patterns in Metastatic Lymph Nodes Reflect the Differential Treatment Response of Advanced Primary Lung Cancer. Cancer Res. 2016 Nov 15;76(22):6568-6576. doi: 10.1158/0008-5472.CAN-16-0873. Epub 2016 Sep 13. — View Citation

Vittinghoff E, McCulloch CE. Relaxing the rule of ten events per variable in logistic and Cox regression. Am J Epidemiol. 2007 Mar 15;165(6):710-8. doi: 10.1093/aje/kwk052. Epub 2006 Dec 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	3-year disease-free survival	To identify a molecular signature based on a comprehensive molecular analysis at genomic and transcriptomic levels linked to 3-year disease-free survival in resected IIIA-N2 NSCLC.	3 years
Secondary	5-year disease-free survival	To identify a molecular signature based on a comprehensive molecular analysis at genomic and transcriptomic levels linked to 5-year disease-free survival in resected IIIA-N2 NSCLC.	5 years
Secondary	pathological architectural patterns WHO 2015 classification	To evaluate the impact of the pathological architectural patterns WHO 2015 classification on the 5-year cancer-specific survival and the 5-year overall survival	5 years
Secondary	anatomical lymphatic spread	To identify tumor molecular patterns associated with specific anatomical lymphatic spread subgroups.	at the end of molecular analyses
Secondary	ctDNA	To assess ctDNA prognostic impact, before and after surgery.	3 years