Adenocarcinoma of LungNCT04122833
Impact of Concomitant Genetic Alterations in EGFR Mutated Adenocarcinoma by NGS Analysis: A Multicenter Study
An observational study of Adenocarcinoma of Lung and EGFR Activating Mutation, run by Konkuk University Medical Center at 2 sites in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Adenocarcinoma of Lung, EGFR Activating Mutation
- What is being tested?
- Next generation sequencing
- How many people
- 80 participants
- Where
- 2 sitesSouth Korea
- Study dates
- 30 Sep 2019to 31 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- Adult, Older adult
Study population: EGFR-mutated stage IV lung adenocarcinoma patients
Who may be able to join
- 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
Who cannot join
- Tumor tissue from bone metastases that have been decalcified are not acceptable.
- -
Trial locations and contacts
2 sites in 1 country.
South Korea2 sites, 2 recruiting
- Recruiting
Asan medical center
Seoul, 05505
Jae Chul Lee, Ph.D
- Not yet recruiting
Catholic university medical center, Seoul St. Mary's Hospital
Seoul
Seung Joon Kim, MD.Ph.D.
About this 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.
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.
Read the 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.
- Conditions
- Adenocarcinoma of Lung, EGFR Activating Mutation
- Being tested
- Next generation sequencing
- Keywords
- next generation sequencing
- Medical subject headings
- Adenocarcinoma of Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Next generation sequencingOther
observational study
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of mutation profiles between pre/post TKI treatment
Comparison of the kinds of the mutation between pre- and post TKI treatment
Measured: through study completion, an average of 1 year
Secondary outcomes (5)
PFS according to the co-occurring mutations with pre-TKI treatment
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
Measured: through study completion, an average of 1 year
The number and the kinds of co-occurring mutations on tumors before and after TKI treatment
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
Measured: 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
The investigators will analyze the correlation with the change of the VAF and PFS in matched tumors tissues before and after TKI treatment
Measured: through study completion, an average of 1 year
Tumor mutation burden in tumors tissues before and after TKI treatment
The investigators will compare the TMB in tumors tissues before and after TKI
Measured: 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
The investigators will compare the concordance of the mutation profile in tumors and blood before TKI treatment
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2019
- Study start30 Sep 2019
- Primary completion30 Sep 2023 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Adenocarcinoma of LungStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Konkuk University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Roche Diagnostics GmbH, Foundation Medicine
- Responsible party
- Principal investigator, Kye Young Lee, Konkuk University Medical Center
- Investigators
- In Ae Kim, MD. Ph.D, Study director, Kunkuk University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04122833
- Sponsor's protocol ID
- ML41560
- Status last verified
- Aug 2022
- First submitted
- 3 Oct 2019
- Last updated
- 18 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 23816960Kim 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.
PubMed 30391576Offin 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.
PubMed 30045933Yu 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.
PubMed 29530932Socinski 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.
PubMed 27821794
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT04122833
- Acronym / sponsor ID
- ML41560
- Conditions
- Adenocarcinoma of Lung, EGFR Activating Mutation
- Keywords
- next generation sequencing
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Konkuk University Medical CenterUniversity, hospital or other
- Collaborators
- Roche Diagnostics GmbH, Foundation Medicine
- Study start
- 30 Sep 2019 (actual)
- Primary completion
- 30 Sep 2023 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 10 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- EGFR-mutated stage IV lung adenocarcinoma patients
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (2 listed)
- Tumor tissue from bone metastases that have been decalcified are not acceptable.
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Next generation sequencingobservational study | Other | – |
Primary outcome
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
5 secondary outcomes
PFS according to the co-occurring mutations with pre-TKI treatment
Time frame: through study completion, an average of 1 year
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 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
Tumor mutation burden in tumors tissues before and after TKI treatment
Time frame: 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
Time frame: through study completion, an average of 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2022.
- Background: PubMed 23816960Sequist 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.
- Background: PubMed 30391576Kim 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.
- Background: PubMed 30045933Offin 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.
- Background: PubMed 29530932Yu 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.
- Background: PubMed 27821794Socinski 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
In Ae Kim, MD. Ph.D study director
Kunkuk University Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Adenocarcinoma of Lung and EGFR Activating Mutation, run by Konkuk University Medical Center at 2 sites in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact In Ae Kim, MD. Ph.D (01035438353, 20180618@kuh.ac.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of mutation profiles between pre/post TKI treatment (time frame: through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04122833, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2022.