Pathogenic Variants in Genes Associated With Lung Adenocarcinoma

NCT ID: NCT06181812

Last Updated: 2025-05-01

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

332 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-12-15

Study Completion Date

2025-12-15

Brief Summary

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The goal of this observational study is to describe the prevalence of germ line-pathogenic variants in Mexican patients with lung adenocarcinoma.

The main questions it aims to answer are:

1. What is the prevalence of pathogenic variants in genes associated with lung adenocarcinoma in Mexican patients younger than fifty?
2. Which clinical-pathological characteristics are associated with germ-line pathogenic variants in patients with lung adenocarcinoma?
3. How actionable somatic mutations are associated with germ line-pathogenic variants of patients with lung adenocarcinoma?

Participants will be asked to sign an informed consent; after that, they will be instructed to donate 10 ml of peripheral blood by venipuncture in the morning and before the patient has taken morning medication and the first meal, following a period of 8-12 hr fasting.

Detailed Description

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This is an observational, descriptive, and longitudinal study.

The sample size was calculated with a proportion difference formula for a known population, considering the Local Institutional Personalized Medicine Laboratory tests 100 blood samples per year from patients with non-small cell lung cancer (NSCLC). It was considered a 95% confidence level and an 80% power. In addition, a 10% loss in follow-up was estimated.

After reviewing the inclusion and exclusion criteria, signing the informed consent, and peripheral blood sampling. Total DNA (tDNA) will be extracted using the DNAeasy Blood \& Tissue (Qiagen) kit.

Likewise, for the determination of pathogenic variants, the Sophia HCS Community panels (Sophia genetics) will be used to carry out Next-generation (NGS) sequencing in a NextSeq 550 (Illumina) platform.

To determine the clinical significance of genomic variants, the data analysis will be performed on the SOPHiA Alamut™ Visual Plus which is a comprehensive, full genome browser for efficient and user-friendly variant interpretation.

Conditions

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Lung Adenocarcinoma

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

OTHER

Eligibility Criteria

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Inclusion Criteria

* Both sexes
* ≥ 16 years old, according the institutional protocols for new patients admittances.
* histologically confirmed lung adenocarcinoma (LUAD)
* Signed written informed consent form
* A life expectancy greater than 8 weeks.
* Histologically confirmed LUAD and one of the following conditions: i) LCFH, defined as having one first-degree relative (FDR) or two or more second-degree relatives with LC, irrespective of the age at diagnosis. ii) Age at diagnosis ≤50 years, or ≤60 with a pack-years index. iii) Presence of ≥1 AGAs (EGFR, ALK, ROS1, KRAS, BRAF, MET exon 14 skipping, or RET).

Exclusion Criteria

* A sample of peripheral blood that is not accessible.
* Insufficient clinical pathological information in the electronic clinical record.

Elimination Criteria:

* Withdrawal
* Insufficient DNA quality and quantity for genomic sequencing analyses.
* Lost of follow up
Minimum Eligible Age

16 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Oscar Gerardo Arrieta Rodríguez

OTHER

Sponsor Role lead

Responsible Party

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Oscar Gerardo Arrieta Rodríguez

Coordinator of the Thoracic Oncology Unit and Laboratory of Personalized Medicine

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Oscar G Arrieta Rodriguez, M.D., M.Sc.

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Cancerologia de Mexico

Locations

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Thoracic Oncology Unit and Personalized Medicine Laboratory, Instituto Nacional de Cancerología

Mexico City, , Mexico

Site Status RECRUITING

Countries

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Mexico

Central Contacts

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Oscar G Arrieta Rodriguez, M.D., M.Sc.

Role: CONTACT

5556280400 ext. 71101

Facility Contacts

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Oscar G Arrieta Rodriguez, M.D., M.Sc.

Role: primary

5556280400 ext. 71101

References

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Sorscher S, LoPiccolo J, Heald B, Chen E, Bristow SL, Michalski ST, Nielsen SM, Lacoste A, Keyder E, Lee H, Nussbaum RL, Martins R, Esplin ED. Rate of Pathogenic Germline Variants in Patients With Lung Cancer. JCO Precis Oncol. 2023 Sep;7:e2300190. doi: 10.1200/PO.23.00190.

Reference Type BACKGROUND
PMID: 37992258 (View on PubMed)

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022 Jan;72(1):7-33. doi: 10.3322/caac.21708. Epub 2022 Jan 12.

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Kumar R, Castillero F, Bhandari S, Malapati S, Kloecker G. The Hispanic Paradox in Non-Small Cell Lung Cancer. Hematol Oncol Stem Cell Ther. 2022 Jun 1;15(2):21-29. doi: 10.1016/j.hemonc.2021.02.004.

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Mukherjee S, Bandlamudi C, Hellmann MD, Kemel Y, Drill E, Rizvi H, Tkachuk K, Khurram A, Walsh MF, Zauderer MG, Mandelker D, Topka S, Zehir A, Srinivasan P, Esai Selvan M, Carlo MI, Cadoo KA, Latham A, Hamilton JG, Liu YL, Lipkin SM, Belhadj S, Bond GL, Gumus ZH, Klein RJ, Ladanyi M, Solit DB, Robson ME, Jones DR, Kris MG, Vijai J, Stadler ZK, Amos CI, Taylor BS, Berger MF, Rudin CM, Offit K. Germline Pathogenic Variants Impact Clinicopathology of Advanced Lung Cancer. Cancer Epidemiol Biomarkers Prev. 2022 Jul 1;31(7):1450-1459. doi: 10.1158/1055-9965.EPI-21-1287.

Reference Type BACKGROUND
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Peng W, Li B, Li J, Chang L, Bai J, Yi Y, Chen R, Zhang Y, Chen C, Pu X, Jiang M, Li J, Zhong R, Xu F, Chen B, Xu L, Wang N, Huan J, Dai P, Guan Y, Yang L, Xia X, Yi X, Wang J, Yu F, Wu L. Clinical and genomic features of Chinese lung cancer patients with germline mutations. Nat Commun. 2022 Mar 10;13(1):1268. doi: 10.1038/s41467-022-28840-5.

Reference Type BACKGROUND
PMID: 35273153 (View on PubMed)

Carrot-Zhang J, Soca-Chafre G, Patterson N, Thorner AR, Nag A, Watson J, Genovese G, Rodriguez J, Gelbard MK, Corrales-Rodriguez L, Mitsuishi Y, Ha G, Campbell JD, Oxnard GR, Arrieta O, Cardona AF, Gusev A, Meyerson M. Genetic Ancestry Contributes to Somatic Mutations in Lung Cancers from Admixed Latin American Populations. Cancer Discov. 2021 Mar;11(3):591-598. doi: 10.1158/2159-8290.CD-20-1165. Epub 2020 Dec 2.

Reference Type BACKGROUND
PMID: 33268447 (View on PubMed)

Gerson R, Zatarain-Barron ZL, Blanco C, Arrieta O. Access to lung cancer therapy in the Mexican population: opportunities for reducing inequity within the health system. Salud Publica Mex. 2019 May-Jun;61(3):352-358. doi: 10.21149/10118.

Reference Type BACKGROUND
PMID: 31276352 (View on PubMed)

Wang Y, McKay JD, Rafnar T, Wang Z, Timofeeva MN, Broderick P, Zong X, Laplana M, Wei Y, Han Y, Lloyd A, Delahaye-Sourdeix M, Chubb D, Gaborieau V, Wheeler W, Chatterjee N, Thorleifsson G, Sulem P, Liu G, Kaaks R, Henrion M, Kinnersley B, Vallee M, LeCalvez-Kelm F, Stevens VL, Gapstur SM, Chen WV, Zaridze D, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, Krokan HE, Gabrielsen ME, Skorpen F, Vatten L, Njolstad I, Chen C, Goodman G, Benhamou S, Vooder T, Valk K, Nelis M, Metspalu A, Lener M, Lubinski J, Johansson M, Vineis P, Agudo A, Clavel-Chapelon F, Bueno-de-Mesquita HB, Trichopoulos D, Khaw KT, Johansson M, Weiderpass E, Tjonneland A, Riboli E, Lathrop M, Scelo G, Albanes D, Caporaso NE, Ye Y, Gu J, Wu X, Spitz MR, Dienemann H, Rosenberger A, Su L, Matakidou A, Eisen T, Stefansson K, Risch A, Chanock SJ, Christiani DC, Hung RJ, Brennan P, Landi MT, Houlston RS, Amos CI. Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer. Nat Genet. 2014 Jul;46(7):736-41. doi: 10.1038/ng.3002. Epub 2014 Jun 1.

Reference Type BACKGROUND
PMID: 24880342 (View on PubMed)

Esai Selvan M, Zauderer MG, Rudin CM, Jones S, Mukherjee S, Offit K, Onel K, Rennert G, Velculescu VE, Lipkin SM, Klein RJ, Gumus ZH. Inherited Rare, Deleterious Variants in ATM Increase Lung Adenocarcinoma Risk. J Thorac Oncol. 2020 Dec;15(12):1871-1879. doi: 10.1016/j.jtho.2020.08.017. Epub 2020 Aug 28.

Reference Type BACKGROUND
PMID: 32866655 (View on PubMed)

Other Identifiers

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(022/056/ICI)(CEI/057/22)

Identifier Type: -

Identifier Source: org_study_id

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