Lung CancerNCT04814407
Developing Novel Circulating Epigenetic Biomarkers for Early Detection of Lung Cancer
An observational study of Lung Cancer, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
The investigators aim to identify novel circulating methylated biomarkers for early lung cancer detection as well as to develop new technologies that are clinically applicable with high sensitivity and specificity. Read more about this study
- Who is it for?
- Ages 20 years and olderHealthy volunteers can take part
- Conditions the study is for
- Lung Cancer
- What is being tested?
- Blood-derived DNA methylation detection
- How many people
- 900 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Mar 2021to 31 Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 20 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: 1. Study subjects: Patients with suspected or confirmed diagnosis of lung cancer. 2. Indeterminate subjects: Subjects who had indeterminate sub-centimeter pulmonary nodules or ground glass opacities discovered by computed tomography. 3. Control subjects: Non-cancer subjects including healthy volunteers, chronic inflammatory airway diseases such as chronic obstructive airway disease, asthma, and bronchiectasis, etc.
Who may be able to join
- Subjects suspected or confirmed diagnosis of lung cancer.
- Subjects who had indeterminate sub-centimeter pulmonary nodules or ground glass opacities discovered by computed tomography.
- Non-cancer subjects: including healthy volunteers and chronic inflammatory airway diseases such as chronic obstructive airway disease, asthma, and bronchiectasis, etc.
- Subjects age over 20.
Who cannot join
- Pregnancy.
- Subjects with HIV infection.
- Unable to or unwilling to give informed consent.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Taiwan1 site, 1 recruiting
- Recruiting
National Taiwan University Hospital
Taipei, 100225
Hsing-Chen Tsai, M.D., Ph.D, +886-2-23123456 ext. 88797, htsai@ntu.edu.tw
About this study
The investigators aim to identify novel circulating methylated biomarkers for early lung cancer detection as well as to develop new technologies that are clinically applicable with high sensitivity and specificity.
Read the detailed description
Lung cancer is the leading cause of cancer death, accounting for 2.09 million cases in 2018 worldwide. There is a huge demand globally for sensitive and reliable assays to intercept lung cancer at early stages when it can be cured. Past studies have shown that circulating cell-free tumor DNA (ctDNA) shed from tumor cells contains the same mutations and methylation patterns as the original tumor cells. Emerging evidence has indicated the presence of systemic immune dysregulation in cancer patients, and that tumor-reactive T cells carry a distinct molecular profile compared to other bystander cells. Thus, molecular abnormality of ctDNA and tumor-reactive T cells may be one of the early signs that hint the presence of malignancy, and it may serve as a promising target for development of blood-based assays in early lung cancer for its convenience and non-invasiveness as opposed to invasive tumor biopsy, or imaging-based methods that are limited by unsatisfactory sensitivity/specificity.
The investigators aim to identify novel markers for early lung cancer detection as well as to develop new technologies that are clinically applicable with high sensitivity and specificity. The objectives of this proposal are multifaceted: (1) The investigators will generate genome-wide methylation atlas of circulating cell free DNA and of circulating T cells in lung cancer patients vs. non-cancer subjects. (2) The investigators will develop an enriched method to enhance the performance of multiplex droplet digital PCR (ddPCR) technology with increased sensitivity and decreased input DNA requirement. (Enriched methylation-specific droplet digital PCR, EMS-ddPCR) (3) The investigators will develop a single-cell, locus-specific DNA methylation detection system that is bisulfite-free and non-PCR-based. The system can be coupled with flow cytometry or mass cytometry to enable cell-type specific methylation detection. (single-cell, locus-specific methylation detection, scLSM-FACS) (4) The investigators will identify a novel methylation signature consisting of tumor-derived and immune-derived biomarkers for early detection of lung cancer.
- Conditions
- Lung Cancer
- Being tested
- Blood-derived DNA methylation detection
- Keywords
- Lung cancer, Cell-free DNA, DNA methylation, T cell methylome, cell-free tumor DNA (ctDNA)
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood-derived DNA methylation detectionDiagnostic test
Up to 20 ml of blood will be collected from each subject, and the blood specimen will be processed to isolate plasma cell-free DNA and immune-derived cells (circulating T cells). Circulating methylated tumor/immune signature will then be identified.
| Study group | Role | What they receive |
|---|---|---|
| Lung cancer patients | Patients age over 20, with suspected or confirmed diagnosis of lung cancer. Receives: Diagnostic Test: Blood-derived DNA methylation detection | |
| Indeterminate subjects | Subjects who had indeterminate sub-centimeter pulmonary nodules or ground glass opacities discovered by computed tomography. Receives: Diagnostic Test: Blood-derived DNA methylation detection | |
| Control subjects | Non-cancer patients including healthy volunteers, chronic inflammatory airway diseases such as chronic obstructive airway disease, asthma, and bronchiectasis, etc. Receives: Diagnostic Test: Blood-derived DNA methylation detection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of circulating tumor and immune methylated signature
Genome-wide methylation profile of lung cancer patients and control subjects will be measured both in circulating T cells and cell-free DNA collected from peripheral blood by using Infinium MethylationEPIC BeadChip platform.
Measured: 1 year
Technology development
The investigators will develop enriched methylation-specific droplet digital PCR (EMS-ddPCR) with increased sensitivity and decreased input DNA requirement. The investigators will develop single-cell, locus-specific DNA methylation detection system for flow cytometry (scLSM-FACS) to enable cell-type specific methylation detection.
Measured: 1 year
Technology validation
The investigators will validate the identified circulating methylated signature in patients with indeterminate pulmonary nodules.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2021
- Study start1 Mar 2021
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 900 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hsing-Chen Tsai, M.D., Ph.D, Study chair, Graduate institute of Toxicology, NTUCM; Department of Internal Medicine, NTUH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04814407
- Sponsor's protocol ID
- 202012096RIPC
- Status last verified
- Jun 2024
- First submitted
- 22 Mar 2021
- Last updated
- 18 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Developing Novel Circulating Epigenetic Biomarkers for Early Detection of Lung Cancer
- ClinicalTrials.gov ID
- NCT04814407
- Acronym / sponsor ID
- 202012096RIPC
- Conditions
- Lung Cancer
- Keywords
- Lung cancer, Cell-free DNA, DNA methylation, T cell methylome, cell-free tumor DNA (ctDNA)
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 900 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 24 Mar 2021 (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 investigators aim to identify novel circulating methylated biomarkers for early lung cancer detection as well as to develop new technologies that are clinically applicable with high sensitivity and specificity.
Detailed description
Lung cancer is the leading cause of cancer death, accounting for 2.09 million cases in 2018 worldwide. There is a huge demand globally for sensitive and reliable assays to intercept lung cancer at early stages when it can be cured. Past studies have shown that circulating cell-free tumor DNA (ctDNA) shed from tumor cells contains the same mutations and methylation patterns as the original tumor cells. Emerging evidence has indicated the presence of systemic immune dysregulation in cancer patients, and that tumor-reactive T cells carry a distinct molecular profile compared to other bystander cells. Thus, molecular abnormality of ctDNA and tumor-reactive T cells may be one of the early signs that hint the presence of malignancy, and it may serve as a promising target for development of blood-based assays in early lung cancer for its convenience and non-invasiveness as opposed to invasive tumor biopsy, or imaging-based methods that are limited by unsatisfactory sensitivity/specificity.
The investigators aim to identify novel markers for early lung cancer detection as well as to develop new technologies that are clinically applicable with high sensitivity and specificity. The objectives of this proposal are multifaceted: (1) The investigators will generate genome-wide methylation atlas of circulating cell free DNA and of circulating T cells in lung cancer patients vs. non-cancer subjects. (2) The investigators will develop an enriched method to enhance the performance of multiplex droplet digital PCR (ddPCR) technology with increased sensitivity and decreased input DNA requirement. (Enriched methylation-specific droplet digital PCR, EMS-ddPCR) (3) The investigators will develop a single-cell, locus-specific DNA methylation detection system that is bisulfite-free and non-PCR-based. The system can be coupled with flow cytometry or mass cytometry to enable cell-type specific methylation detection. (single-cell, locus-specific methylation detection, scLSM-FACS) (4) The investigators will identify a novel methylation signature consisting of tumor-derived and immune-derived biomarkers for early detection of lung cancer.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Lung cancer patients | – | Diagnostic Test: Blood-derived DNA methylation detectionPatients age over 20, with suspected or confirmed diagnosis of lung cancer. |
| Indeterminate subjects | – | Diagnostic Test: Blood-derived DNA methylation detectionSubjects who had indeterminate sub-centimeter pulmonary nodules or ground glass opacities discovered by computed tomography. |
| Control subjects | – | Diagnostic Test: Blood-derived DNA methylation detectionNon-cancer patients including healthy volunteers, chronic inflammatory airway diseases such as chronic obstructive airway disease, asthma, and bronchiectasis, etc. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 1. Study subjects: Patients with suspected or confirmed diagnosis of lung cancer. 2. Indeterminate subjects: Subjects who had indeterminate sub-centimeter pulmonary nodules or ground glass opacities discovered by computed tomography. 3. Control subjects: Non-cancer subjects including healthy volunteers, chronic inflammatory airway diseases such as chronic obstructive airway disease, asthma, and bronchiectasis, etc.
Key inclusion criteria (4 listed)
- Subjects suspected or confirmed diagnosis of lung cancer.
- Subjects who had indeterminate sub-centimeter pulmonary nodules or ground glass opacities discovered by computed tomography.
- Non-cancer subjects: including healthy volunteers and chronic inflammatory airway diseases such as chronic obstructive airway disease, asthma, and bronchiectasis, etc.
- Subjects age over 20.
Key exclusion criteria (3 listed)
- Pregnancy.
- Subjects with HIV infection.
- Unable to or unwilling to give informed consent.
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 |
|---|---|---|
| Blood-derived DNA methylation detectionUp to 20 ml of blood will be collected from each subject, and the blood specimen will be processed to isolate plasma cell-free DNA and immune-derived cells (circulating T cells). Circulating methylated tumor/immune signature will then be identified. | Diagnostic test | Control subjects, Indeterminate subjects, Lung cancer patients |
Primary outcome
Identification of circulating tumor and immune methylated signature
Time frame: 1 year
Genome-wide methylation profile of lung cancer patients and control subjects will be measured both in circulating T cells and cell-free DNA collected from peripheral blood by using Infinium MethylationEPIC BeadChip platform.
Technology development
Time frame: 1 year
The investigators will develop enriched methylation-specific droplet digital PCR (EMS-ddPCR) with increased sensitivity and decreased input DNA requirement. The investigators will develop single-cell, locus-specific DNA methylation detection system for flow cytometry (scLSM-FACS) to enable cell-type specific methylation detection.
Technology validation
Time frame: 1 year
The investigators will validate the identified circulating methylated signature in patients with indeterminate pulmonary nodules.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2024.
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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.
Hsing-Chen Tsai, M.D., Ph.D study chair
Graduate institute of Toxicology, NTUCM; Department of Internal Medicine, NTUH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lung Cancer, run by National Taiwan University Hospital at 1 site in Taiwan.
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 4 inclusion and 3 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: looking for participants now, as of the sponsor's last update on 18 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hsing-Chen Tsai, M.D., Ph.D (+886-2-23123456 ext. 88797, htsai@ntu.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of circulating tumor and immune methylated signature (time frame: 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Jun 2024.