Impact of Concomitant Genetic Alterations in EGFR Mutated Adenocarcinoma by NGS Analysis: A Multicenter Study

NCT04122833 | Unknown

• 1 other identifier: ML41560
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

The concomitant co-mutation with epidermal growth factor receptor (EGFR) mutation might influence the clinical outcomes. The investigators will identify the impact of concommitant mutation on clinical outcome in patients with advanced -EGFR mutated adenocarcinoma. The investigators will compare the genetic alterations between tumors of pre and post Tyrosin Kinase Inhibitor(TKI) treatments and predict the resistance mechanism for EGFR-TKIs by next-generation sequencing(NGS) analysis.

Conditions

Adenocarcinoma of Lung; EGFR Activating Mutation

Keywords

next generation sequencing

Outcome Measures

Primary Outcomes (1)

• Change of mutation profiles between pre/post TKI treatment

  Comparison of the kinds of the mutation between pre- and post TKI treatment

  through study completion, an average of 1 year

Secondary Outcomes (5)

• PFS according to the co-occurring mutations with pre-TKI treatment

  through study completion, an average of 1 year

• The number and the kinds of co-occurring mutations on tumors before and after TKI treatment

  through study completion, an average of 1 year

• The correlation between the change of variant allele frequency(VAF) and drug response in matched tumors tissues before and after TKI treatment

  through study completion, an average of 1 year

• Tumor mutation burden in tumors tissues before and after TKI treatment

  through study completion, an average of 1 year

• The concordance the the mutation profiles in the NGS results of tissue and blood in the same patients

  through study completion, an average of 1 year

Interventions

Next generation sequencing OTHER

observational study

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

EGFR-mutated stage IV lung adenocarcinoma patients

You may qualify if:

• Signed Informed Consent Form
• Age ≥19 years
• EGFR-mutated stage IV lung adenocarcinoma patients
• Archival biopsy tissues which are from core needle biopsies, endobronchial ultrasound (EBUS) guided- lymph node biopsy or lymph node excisional biopsy at baseline and at radiologic progression
• Availability of the 10 unstained slides and 1 H\&E slides at pre/ post TKI treatment
• Samples should contain a minimum of 20% viable tumor cells that preserve

You may not qualify if:

• Tumor tissue from bone metastases that have been decalcified are not acceptable.

Sponsors & Collaborators

• Konkuk University Medical Center: lead
• Roche Diagnostics GmbH: collaborator
• Foundation Medicine: collaborator

Study Sites (2)

Asan medical center

Seoul, 05505, South Korea

RECRUITING

Catholic university medical center, Seoul St. Mary's Hospital

Seoul, South Korea

NOT YET RECRUITING

Related Publications (5)

• Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. doi: 10.1200/JCO.2012.44.2806. Epub 2013 Jul 1.

  PMID: 23816960 BACKGROUND

• Kim Y, Lee B, Shim JH, Lee SH, Park WY, Choi YL, Sun JM, Ahn JS, Ahn MJ, Park K. Concurrent Genetic Alterations Predict the Progression to Target Therapy in EGFR-Mutated Advanced NSCLC. J Thorac Oncol. 2019 Feb;14(2):193-202. doi: 10.1016/j.jtho.2018.10.150. Epub 2018 Nov 1.

  PMID: 30391576 BACKGROUND

• Offin M, Rizvi H, Tenet M, Ni A, Sanchez-Vega F, Li BT, Drilon A, Kris MG, Rudin CM, Schultz N, Arcila ME, Ladanyi M, Riely GJ, Yu H, Hellmann MD. Tumor Mutation Burden and Efficacy of EGFR-Tyrosine Kinase Inhibitors in Patients with EGFR-Mutant Lung Cancers. Clin Cancer Res. 2019 Feb 1;25(3):1063-1069. doi: 10.1158/1078-0432.CCR-18-1102. Epub 2018 Jul 25.

  PMID: 30045933 BACKGROUND

• Yu HA, Suzawa K, Jordan E, Zehir A, Ni A, Kim R, Kris MG, Hellmann MD, Li BT, Somwar R, Solit DB, Berger MF, Arcila M, Riely GJ, Ladanyi M. Concurrent Alterations in EGFR-Mutant Lung Cancers Associated with Resistance to EGFR Kinase Inhibitors and Characterization of MTOR as a Mediator of Resistance. Clin Cancer Res. 2018 Jul 1;24(13):3108-3118. doi: 10.1158/1078-0432.CCR-17-2961. Epub 2018 Mar 12.

  PMID: 29530932 BACKGROUND

• Socinski MA, Villaruz LC, Ross J. Understanding Mechanisms of Resistance in the Epithelial Growth Factor Receptor in Non-Small Cell Lung Cancer and the Role of Biopsy at Progression. Oncologist. 2017 Jan;22(1):3-11. doi: 10.1634/theoncologist.2016-0285. Epub 2016 Nov 7.

  PMID: 27821794 BACKGROUND

MeSH Terms

Conditions

Adenocarcinoma of Lung

Interventions

High-Throughput Nucleotide Sequencing

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Sequence Analysis; Genetic Techniques; Investigative Techniques

Study Officials

• In Ae Kim, MD. Ph.D

  Kunkuk University Medical Center

  STUDY DIRECTOR

Central Study Contacts

In Ae Kim, MD. Ph.D

CONTACT

01035438353; 20180618@kuh.ac.kr

Kye Young Lee, MD. Ph.D

CONTACT

01088963916; kykeemd@kuh.ac.kr

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 3, 2019
• First Posted: October 10, 2019
• Study Start: September 30, 2019
• Primary Completion: September 30, 2023
• Study Completion: December 31, 2024
• Last Updated: August 18, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

KR (2)