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

• ClinicalTrials.gov Identifier: NCT04122833
• Recruitment Status: Recruiting
• First Posted: October 10, 2019
• Last Update Posted: October 10, 2019
• Sponsor: Konkuk University Medical Center
• Collaborators: Roche Diagnostics; Foundation Medicine
• Information provided by (Responsible Party): Kye Young Lee, Konkuk University Medical Center

Tracking Information

• First Submitted Date: October 3, 2019
• First Posted Date: October 10, 2019
• Last Update Posted Date: October 10, 2019
• Actual Study Start Date: September 30, 2019
• Estimated Primary Completion Date: September 30, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 9, 2019)

Change of mutation profiles between pre/post TKI treatment [ Time Frame: through study completion, an average of 1 year ]

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

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: October 9, 2019)

• PFS according to the co-occurring mutations with pre-TKI treatment [ Time Frame: through study completion, an average of 1 year ]
  The investigators will compared the PFS according to the kinds of co-occuring genetic alteration in patient with EGFR -mutated adenocarcinoma before the EGFR TKI treatment
• The number and the kinds of co-occurring mutations on tumors before and after TKI treatment [ Time Frame: through study completion, an average of 1 year ]
  The investigators will collect the information about the number and the kinds of co-occurring mutations on tumors before and after TKI treatment in Foundation medicine NGS
• The correlation between the change of variant allele frequency(VAF) and drug response in matched tumors tissues before and after TKI treatment [ Time Frame: through study completion, an average of 1 year ]
  The investigators will analyze the correlation with the change of the VAF and PFS in matched tumors tissues before and after TKI treatment
• Tumor mutation burden in tumors tissues before and after TKI treatment [ Time Frame: through study completion, an average of 1 year ]
  The investigators will compare the TMB in tumors tissues before and after TKI
• The concordance the the mutation profiles in the NGS results of tissue and blood in the same patients [ Time Frame: through study completion, an average of 1 year ]
  The investigators will compare the concordance of the mutation profile in tumors and blood before TKI treatment

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Impact of Concomitant Genetic Alterations in EGFR Mutated Adenocarcinoma by NGS Analysis: A Multicenter Study
• Official Title: A Next-generation Sequencing Analysis to Investigate the Clinical Impact of Concomitant Genetic Alterations in the Patients With Advanced EGFR-mutated Lung Adenocarcinoma: A Multicenter Study.

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.

Detailed Description

The current standard therapies in the treatment of advanced EGFR-mutated lung cancer patients are the 1st or 2nd EGFR-TKIs. Although 70-80% of patients treated by EGFR-TKIS show good responses, they have progression after around 12 months. The concomitant co-mutation with EGFR mutation might influence the drug response of EGFR TKI. The investigators will compare the progression-free survival (PFS) of EGFR-TKI according to co-occuring mutations.

The patients experience the change of molecular profiles after using the TKI. Therefore, the investigators will investigate the molecular profiles through NGS panel with foundation medicine in the tissue of pre/post EGFR-TKI, compare the change of the molecular profiles and tumor mutation burden(TMB), and identify novel mechanisms of drug resistance.

The investigators will collect the tumor tissues and blood of around 80 patients in multi-centers prospectively. Then, They will be sent to FoundationOne in the US and perform NGS analysis. The type of EGFR-TKIs would be selected according to physicians' preference. NGS will be performed twice before the EGFR-TKIs treatment and after the progression.

• Study Type: Observational
• Study Design: Observational Model: Case-Only; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Probability Sample
• Study Population: EGFR-mutated stage IV lung adenocarcinoma patients

Condition

• Adenocarcinoma of Lung
• EGFR Activating Mutation

Intervention

Other: Next generation sequencing

observational study

• Study Groups/Cohorts: Not Provided

Publications *

• 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.
• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 9, 2019): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2021
• Estimated Primary Completion Date: September 30, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Signed Informed Consent Form
2. Age ≥19 years
3. EGFR-mutated stage IV lung adenocarcinoma patients
4. 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
5. Availability of the 10 unstained slides and 1 H&E slides at pre/ post TKI treatment
6. Samples should contain a minimum of 20% viable tumor cells that preserve

Exclusion Criteria:

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

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Sex/Gender

• Sexes Eligible for Study: All

• Ages: 19 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Not Provided

Contacts

Contact: In Ae Kim, MD. Ph.D; 01035438353; 20180618@kuh.ac.kr

Contact: Kye Young Lee, MD. Ph.D; 01088963916; kykeemd@kuh.ac.kr

• Listed Location Countries: Korea, Republic of

Administrative Information

• NCT Number: NCT04122833
• Other Study ID Numbers: ML41560
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Kye Young Lee, Konkuk University Medical Center
• Study Sponsor: Konkuk University Medical Center

Collaborators

• Roche Diagnostics
• Foundation Medicine

Investigators

• Study Director: In Ae Kim, MD. Ph.D; Kunkuk University Medical Center

• PRS Account: Konkuk University Medical Center
• Verification Date: October 2019