Feasibility of Cell-Free DNA Liquid Biopsy in Screening High-Risk Patients for Lung Cancer

Study Overview
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Brief Summary
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This clinical trial investigates how practical and doable (feasibility) cell-free deoxyribonucleic acid (DNA) liquid biopsy is in screening high-risk patients for lung cancer. Currently, a low dose computed tomography (CT) scan is used to screen for lung cancer, however, due to various factors, few high-risk patients are screened. Liquid biopsy utilizes technology that can detect small amounts of DNA shed by cancer cells and may be able to spot lung cancer at an earlier stage. If a positive result comes back from the liquid biopsy, a patient may be more willing to get a low dose CT (LDCT) scan, possibly confirming the biopsy's findings and thus leading to more early lung cancer detection.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine the feasibility of lung cancer screening using liquid biopsy in a community setting. SECONDARY OBJECTIVES: I. To determine screening follow-through rates in those who agreed to undergo screening by preferred modality (liquid biopsy versus [vs] LDCT). II. To determine the rate of LDCT following liquid biopsy (in those who underwent liquid biopsy) after stratifying by test result (negative versus positive). III. To compare participant sociodemographic factors (age, sex, race/ethnicity, educational background) and survey scores across screening preference (liquid biopsy vs. LDCT). OUTLINE: Participants choose 1 of 2 cohorts. COHORT A: Participants undergo collection of blood sample (liquid biopsy), with option to undergo LDCT if liquid biopsy results are positive. COHORT B: Participants undergo low dose CT with optional liquid biopsy on the same day as LDCT. After completion of study, patients are followed up at 6 months.

Official Title
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Feasibility Study of Lung Cancer Screening Using Cell-Free DNA Liquid Biopsy at Home in High-Risk Current and Former Smokers

Conditions
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Lung Carcinoma

Intervention / Treatment
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* Procedure: Liquid Biopsy
* Procedure: Low Dose Computed Tomography of the Chest
* Other: Survey Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented written informed consent of the participant. Age 50-80 years. Smoking history of >= 20 pack-years and if quit, quit within 15 years. Received referral for counseling for lung cancer screening and would qualify for LDCT. Health Insurance that will pay for a LDCT for lung cancer screening at either City of Hope Duarte, Newport Beach (Newport Diagnostic Imaging), or Lancaster (Renaissance Imaging/Antelope Valley Outpatient Imaging Center). Willingness to provide blood sample. English speaking. Consent to undergo lung cancer screening with either liquid biopsy (LB) or LDCT. Exclusion Criteria: Symptoms of lung cancer. Chest CT scan or chest positron emission tomography (PET)/CT within 12 months. Any cancer diagnosis within past 5 years, excluding non-melanoma skin cancer. Unable to undergo LDCT at either City of Hope Duarte, Newport Beach, or Lancaster.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A (liquid biopsy, optional LDCT)<br>Participants undergo collection of blood sample (liquid biopsy), with option to undergo LDCT if liquid biopsy results are positive. | Procedure: Liquid Biopsy<br>* Undergo liquid biopsy<br>* Other names: Plasma Biopsy;Procedure: Low Dose Computed Tomography of the Chest<br>* Undergo low dose CT<br>* Other names: Low-dose Chest CT;Other: Survey Administration<br>* Ancillary studies<br>|
| Experimental: Cohort B (LDCT, optional liquid biopsy)<br>Participants undergo low dose CT with optional liquid biopsy on the same day as LDCT. | Procedure: Liquid Biopsy<br>* Undergo liquid biopsy<br>* Other names: Plasma Biopsy;Procedure: Low Dose Computed Tomography of the Chest<br>* Undergo low dose CT<br>* Other names: Low-dose Chest CT;Other: Survey Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Screening preference | The proportion of participants who agree to undergo lung cancer screening using liquid biopsy versus LDCT, with a feasibility threshold of at least 30% preferring liquid biopsy. | Upon completion of home liquid biopsy or LDCT, an average of 4 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants who follow-through on screening 1 | The proportion of participants who are screened with LDCT at 6 months in each screening group. | 6 month follow-up timepoint. | 
| Participants who follow-through on screening 2 | The proportion of participants who undergo LDCT at 6 months after receiving liquid biopsy results, stratified by test result (negative vs positive). | 6 month follow-up timepoint. | 
| Participants who follow-through on screening 3 | Differences in sociodemographic factors across screening preference (liquid biopsy vs. LDCT) in those who undergo screening (Exploratory). | 6 month follow-up timepoint. | 
| Participants who follow-through on screening 4 | Differences in sociodemographic survey scores across screening preference (liquid biopsy vs. LDCT) in those who undergo screening (Exploratory). | 6 month follow-up timepoint. | 
| Participants who undergo low dose computed tomography of the chest (LDCT) after receiving liquid biopsy results | For those who choose liquid biopsy only. Data will be summarized using counts and percentages and tested using Chi-square analysis. | Up to 6 months | 
| Sociodemographic factors (age, sex, race/ethnicity, educational background) | Data will be summarized using means and standard deviations or counts and percentages, depending on whether the data are continuous or categorical. Univariate tests across groups will be done using t-tests (continuous) and chi-square analysis (categorical). Non-parametric tests will be used for continuous data that are non-normally distributed data (Kruskal-Wallis) and for ordinal categorical data (Jonckheere-Terpstra). Multivariable logistic regression methods will be used to determine the primary factors predicting screening preference. Data included in the model will be determined based on clinical relevance and/or significance in univariate analysis. | At baseline visit | 
| Survey scores across screening preference 1 | Survey tools will be used to understand sociodemographics, prior cancer screening, cancer worry, lung cancer risk perception, and barriers to lung cancer screening. Survey tools utilized:Demographics tool: including sex, race/ethnicity, education level, income. | At 6 month follow up | 
| Survey scores across screening preference 2 | Survey tools will be used to understand sociodemographics, prior cancer screening, cancer worry, lung cancer risk perception, and barriers to lung cancer screening. Survey tools utilized: Tobacco smoking history | At 6 month follow up | 
| Survey scores across screening preference 3 | Survey tools will be used to understand sociodemographics, prior cancer screening, cancer worry, lung cancer risk perception, and barriers to lung cancer screening. Survey tools utilized: Prior use of colon, breast, and lung cancer screening. | At 6 month follow up | 
| Survey scores across screening preference 4 | Survey tools will be used to understand sociodemographics, prior cancer screening, cancer worry, lung cancer risk perception, and barriers to lung cancer screening. Survey tools utilized: Lung Cancer Screening Health Beliefs Survey (lung cancer risk perception and barriers to lung cancer screening). | At 6 month follow up | 
| Survey scores across screening preference 5 | Survey tools will be used to understand sociodemographics, prior cancer screening, cancer worry, lung cancer risk perception, and barriers to lung cancer screening. Survey tools utilized: Cancer Worry Scale | At 6 month follow up |