Molecular Signature From Tumor to Lymph Nodes

NCT ID: NCT04677205

Last Updated: 2023-01-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-03-30

Study Completion Date

2027-11-30

Brief Summary

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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

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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

Conditions

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

Study Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute, France

OTHER_GOV

Sponsor Role collaborator

Ministry of Health, France

OTHER_GOV

Sponsor Role collaborator

Université de Paris

UNKNOWN

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Helene BLONS, PharmD PhD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Européen Georges-Pompidou

Locations

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Hôpital du Haut-Lévêque, CHU de Bordeaux

Bordeaux, , France

Site Status NOT_YET_RECRUITING

Hôpital Militaire Percy

Clamart, , France

Site Status NOT_YET_RECRUITING

Hôpital Nord

Marseille, , France

Site Status NOT_YET_RECRUITING

Hôpital Pasteur, CHU de Nice

Nice, , France

Site Status NOT_YET_RECRUITING

Hegp-Aphp

Paris, , France

Site Status ACTIVE_NOT_RECRUITING

Hôpital Européen Georges-Pompidou

Paris, , France

Site Status RECRUITING

Hôpital Bichat

Paris, , France

Site Status NOT_YET_RECRUITING

Hôpital Cochin

Paris, , France

Site Status NOT_YET_RECRUITING

Hôpital Pontchaillou, CHU de Rennes

Rennes, , France

Site Status NOT_YET_RECRUITING

Hôpitaux universitaires de Strasbourg

Strasbourg, , France

Site Status NOT_YET_RECRUITING

Hôpital Larrey, CHU de Toulouse

Toulouse, , France

Site Status NOT_YET_RECRUITING

CHRU de Tours

Tours, , France

Site Status NOT_YET_RECRUITING

Countries

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France

Central Contacts

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Antoine LEGRAS, MD PhD

Role: CONTACT

33 2 47474747

Liliane HAMMANI-BERKANI, MSc

Role: CONTACT

33 156093762

Facility Contacts

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Jacques JOUGON, Pr

Role: primary

Bertrand GRAND, Dr

Role: primary

Pascal THOMAS, Pr

Role: primary

Jérome MOUROUX, Pr

Role: primary

Françoise LE PIMPEC-BARTHES, Pr

Role: primary

Pierre MORDANT, Dr

Role: primary

Marco ALIFANO, Pr

Role: primary

Bertrand RICHARD DE LA TOUR, PR

Role: primary

MASSARD Gilbert, Pr

Role: primary

Laurent BROUCHET, Pr

Role: primary

Antoine LEGRAS, Dr

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 22642691 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24582052 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23566374 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27624137 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8543964 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25907251 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27634761 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17182981 (View on PubMed)

Other Identifiers

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D20180155

Identifier Type: OTHER

Identifier Source: secondary_id

2019-A02635-52

Identifier Type: OTHER

Identifier Source: secondary_id

D20180155

Identifier Type: -

Identifier Source: org_study_id

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