Non Small Cell Lung CancerNCT04791215
Circulating Tumor DNA Alterations in Non-small Cell Lung Cancer Patients Treated With Pembrolizumab
An observational study of Non Small Cell Lung Cancer, run by Columbia University at 1 site in United States.
Trial summary
The purpose of this study is to learn how to use blood tests to better predict how patients with non-small cell lung cancer, who are taking pembrolizumab for cancer treatment, will respond to treatment with pembrolizumab, and to understand how the immune system and cancer interact. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- Observational
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2020to 12 Apr 2023
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All male and females with a diagnosis of NSCLC with a protein that acts as a kind of "brake" to keep the body's immune responses under control PD-L1 TPS ≥1% and no known alterations in driver genes epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or Proto-oncogene tyrosine-protein kinase (ROS1).
Who may be able to join
- Diagnosis of NSCLC with a protein that acts as a kind of "brake" to keep the body's immune responses under control called Programmed Death Ligand-1 (PD-L1) Tumor Proportion Score (TPS) ≥ 1% and no known alterations in driver genes epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or receptor tyrosine kinase (ROS1).
- Retrospective cohort: subjects must consent to provide genetic data from previous whole exome sequencing (WES) in the form of FASTQ/BAM files (files that represent aligned genetic sequences) for creation of plasma ctDNA panels.
- Prospective cohort: Subjects must consent to provide available archived tumor and blood for WES (matched tumor and normal) for creation of plasma ctDNA panels. The tumor sample must be from a site that was not previously irradiated or has progressed after radiation.
- Ability to understand and the willingness to sign a written informed consent document.
- Willing to comply with clinical trial instructions and requirements.
- Both men and women of all races and ethnic groups are eligible for this trial
Who cannot join
- Age <18 years
- Known history of autoimmune disease or other medical conditions that would preclude safe treatment with pembrolizumab.
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Irving Medical Center
New York, New York, 10032
About this study
Official title: An Observational Study of Circulating Tumor DNA Genetic Alterations in Non-small Cell Lung Cancer Patients Treated With Pembrolizumab
The purpose of this study is to learn how to use blood tests to better predict how patients with non-small cell lung cancer, who are taking pembrolizumab for cancer treatment, will respond to treatment with pembrolizumab, and to understand how the immune system and cancer interact.
Tests will be performed on tumor tissue and blood samples, and imaging assessments will be reviewed in order to monitor how well each patient responds to treatment. This is an observational study, so participants will not receive cancer treatment, other than the treatment received as standard of care.
Read the detailed description
The primary and secondary endpoints of this study are to determine the kinetics of Circulating tumor DNA (ctDNA) as defined by a set of patient-specific tumor mutations. The analysis will be undertaken using the Signatera Assay from Natera. Circulating tumor DNA in plasma samples obtained over the course of pembrolizumab treatment will be assessed by high-intensity, next-generation genetic sequencing to identify genomic alterations in genes. The assay will target 16 defined patient specific mutations. Data acquired will be analyzed to characterize the association between these genetic elements, clinical response, and durability of responses. There will be prospective and retrospective groups for the study. Samples will be collected from patients in the prospective cohort who have been treated with pembrolizumab monotherapy at Columbia University Irving Medical Center under standard of care treatment. Subjects in the retrospective cohort will provide genetic data.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- Observational
- Keywords
- Cancer, Immune system, Lung Cancer, Pembrolizumab
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Neoplasms, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ObservationalOther
All patients will be treated with standard of care pembrolizumab. After obtaining written informed consent, NSCLC participants will have serial blood collection. The blood collection (26 ml) should coincide with routine clinical blood draw to minimize participant discomfort if possible. No additional procedures will be performed other than phlebotomy. If additional biopsies or tumor resection are performed as part of routine standard of care throughout the course of the study, an additional 26 ml blood collection may be drawn for the study. Participants will remain on the study for as long as they are being followed or treated at Columbia University Irving Medical Center. Participants can withdraw from the study at any time.
| Study group | Role | What they receive |
|---|---|---|
| Prospective Sample Collection | Prospective sample collection from participants treated with pembrolizumab monotherapy at Columbia University Irving Medical Center under standard of care treatment. Prospective cohort subjects must consent to provide available archived tumor and blood for whole exome sequencing (WES) (matched tumor and normal) for creation of plasma ctDNA panels. The tumor sample must be from a site that was not previously irradiated or has progressed after radiation. Receives: Other: Observational | |
| Retrospective Sample Collection | Retrospective sample collection from participants that consent to provide genetic data from previous whole exome sequencing (WES) in the form of files for creation of plasma ctDNA panels. Receives: Other: Observational |
What is being measured
The primary outcome is the main question the study is designed to answer.
Radiologic response to immune checkpoint blockade (ICB) by clonal dynamics of serial ctDNA in 1st line NSCLC patients receiving pembrolizumab monotherapy.
Radiologic response to immune checkpoint blockade (ICB) by clonal dynamics of serial ctDNA in 1st line NSCLC participants receiving pembrolizumab monotherapy. Imaging studies will be performed per RECIST 1.1. Radiologic response measured as the average time between randomization and detection of overt progression or response by ctDNA compared to RECIST 1.1.
Measured: 5 years
Secondary outcomes (1)
To characterize kinetic profiles of tumor mutations and see if they are predictive of overall survival (OS) and progression-free survival (PFS).
To characterize kinetic profiles of defined tumor mutations in tumor fraction ctDNA and evaluate whether they are predictive of overall survival (OS) and progression-free survival (PFS). A blood-based ctDNA assay offers the advantage of a read-out of these temporal changes, with the prospect of kinetic assessment of tumor fraction ctDNA being predictive for early response or progression to immunotherapy. The ability to assess temporal changes in tumor genetics will give insight into tumor clonal evolution and immune editing of specific neoantigens, which may enable leveraging of these insights for future diagnostic and therapeutic improvements.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2021
- Study start1 Feb 2020
- Primary completion12 Apr 2023
- Study completion12 Apr 2023
Why it stopped: Low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe 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
- Other
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Brian Henick, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04791215
- Sponsor's protocol ID
- AAAS7953
- Status last verified
- Oct 2024
- First submitted
- 8 Mar 2021
- Last updated
- 26 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Observational Study of Circulating Tumor DNA Genetic Alterations in Non-small Cell Lung Cancer Patients Treated With Pembrolizumab
- ClinicalTrials.gov ID
- NCT04791215
- Acronym / sponsor ID
- AAAS7953
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- Cancer, Immune system, Lung Cancer, Pembrolizumab
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Low accrual
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- 1 Feb 2020 (actual)
- Primary completion
- 12 Apr 2023 (actual)
- Study completion
- 12 Apr 2023 (actual)
- First posted
- 10 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 purpose of this study is to learn how to use blood tests to better predict how patients with non-small cell lung cancer, who are taking pembrolizumab for cancer treatment, will respond to treatment with pembrolizumab, and to understand how the immune system and cancer interact.
Tests will be performed on tumor tissue and blood samples, and imaging assessments will be reviewed in order to monitor how well each patient responds to treatment. This is an observational study, so participants will not receive cancer treatment, other than the treatment received as standard of care.
Detailed description
The primary and secondary endpoints of this study are to determine the kinetics of Circulating tumor DNA (ctDNA) as defined by a set of patient-specific tumor mutations. The analysis will be undertaken using the Signatera Assay from Natera. Circulating tumor DNA in plasma samples obtained over the course of pembrolizumab treatment will be assessed by high-intensity, next-generation genetic sequencing to identify genomic alterations in genes. The assay will target 16 defined patient specific mutations. Data acquired will be analyzed to characterize the association between these genetic elements, clinical response, and durability of responses. There will be prospective and retrospective groups for the study. Samples will be collected from patients in the prospective cohort who have been treated with pembrolizumab monotherapy at Columbia University Irving Medical Center under standard of care treatment. Subjects in the retrospective cohort will provide genetic data.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prospective Sample Collection | – | Other: ObservationalProspective sample collection from participants treated with pembrolizumab monotherapy at Columbia University Irving Medical Center under standard of care treatment. Prospective cohort subjects must consent to provide available archived tumor and blood for whole exome sequencing (WES) (matched tumor and normal) for creation of plasma ctDNA panels. The tumor sample must be from a site that was not previously irradiated or has progressed after radiation. |
| Retrospective Sample Collection | – | Other: ObservationalRetrospective sample collection from participants that consent to provide genetic data from previous whole exome sequencing (WES) in the form of files for creation of plasma ctDNA panels. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All male and females with a diagnosis of NSCLC with a protein that acts as a kind of "brake" to keep the body's immune responses under control PD-L1 TPS ≥1% and no known alterations in driver genes epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or Proto-oncogene tyrosine-protein kinase (ROS1).
Key inclusion criteria (6 listed)
- Diagnosis of NSCLC with a protein that acts as a kind of "brake" to keep the body's immune responses under control called Programmed Death Ligand-1 (PD-L1) Tumor Proportion Score (TPS) ≥ 1% and no known alterations in driver genes epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or receptor tyrosine kinase (ROS1).
- Retrospective cohort: subjects must consent to provide genetic data from previous whole exome sequencing (WES) in the form of FASTQ/BAM files (files that represent aligned genetic sequences) for creation of plasma ctDNA panels.
- Prospective cohort: Subjects must consent to provide available archived tumor and blood for WES (matched tumor and normal) for creation of plasma ctDNA panels. The tumor sample must be from a site that was not previously irradiated or has progressed after radiation.
- Ability to understand and the willingness to sign a written informed consent document.
- Willing to comply with clinical trial instructions and requirements.
Key exclusion criteria (2 listed)
- Age <18 years
- Known history of autoimmune disease or other medical conditions that would preclude safe treatment with pembrolizumab.
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 |
|---|---|---|
| ObservationalAll patients will be treated with standard of care pembrolizumab. After obtaining written informed consent, NSCLC participants will have serial blood collection. The blood collection (26 ml) should coincide with routine clinical blood draw to minimize participant discomfort if possible. No additional procedures will be performed other than phlebotomy. If additional biopsies or tumor resection are performed as part of routine standard of care throughout the course of the study, an additional 26 ml blood collection may be drawn for the study. Participants will remain on the study for as long as they are being followed or treated at Columbia University Irving Medical Center. Participants can withdraw from the study at any time. | Other | Prospective Sample Collection, Retrospective Sample Collection |
Primary outcome
Radiologic response to immune checkpoint blockade (ICB) by clonal dynamics of serial ctDNA in 1st line NSCLC patients receiving pembrolizumab monotherapy.
Time frame: 5 years
Radiologic response to immune checkpoint blockade (ICB) by clonal dynamics of serial ctDNA in 1st line NSCLC participants receiving pembrolizumab monotherapy. Imaging studies will be performed per RECIST 1.1. Radiologic response measured as the average time between randomization and detection of overt progression or response by ctDNA compared to RECIST 1.1.
1 secondary outcome
To characterize kinetic profiles of tumor mutations and see if they are predictive of overall survival (OS) and progression-free survival (PFS).
Time frame: 5 years
Results and safety
The study was stopped early (reason given: Low accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2024.
- Individual participant dataSharing planned: Undecided
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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.
Brian Henick, MD principal investigator
Columbia University
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 Non Small Cell Lung Cancer, run by Columbia University at 1 site in United States.
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: stopped early, as of the sponsor's last update on 26 Oct 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 United States. 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?
The study was stopped early (reason given: Low accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Radiologic response to immune checkpoint blockade (ICB) by clonal dynamics of serial ctDNA in 1st line NSCLC patients receiving pembrolizumab monotherapy. (time frame: 5 years). 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 26 Oct 2024.