Liquid Biopsy for Early Non-small Lung Cancer Detection

Study Overview
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Brief Summary
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This clinical trial will assess the performance of a liquid biopsy assay to identify cancer in indeterminant pulmonary nodules identified by CT screening of high-risk individuals and evaluate the capability of the liquid biopsy assay to monitor response to surgical resection.

Detailed Description
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This clinical study examines the feasibility of a liquid biopsy methylation assay to detect non-small lung cancer. First, the investigators will apply their liquid biopsy assay to screen for lung cancer in indeterminate pulmonary nodules suspicious for cancer. Second, the investigators will assess the utility of liquid biopsy to assess tumor dynamics after surgical resection with curative intent. Third, the investigators will assess the presence or absence of this methylation assay in healthy normal persons without a history of lung cancer.

Official Title
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Liquid Biopsy to Distinguish Malignant From Benign Pulmonary Nodules and to Monitor Response to Therapy

Conditions
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Non Small-cell Lung Cancer

Intervention / Treatment
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* Diagnostic Test: Liquid biopsy for aberrant DNA methylation analysis - Indeterminate pulmonary nodule
* Diagnostic Test: Liquid biopsy for aberrant DNA methylation analysis - Known lung cancer for surgical resection
* Diagnostic Test: Liquid biopsy for aberrant DNA methylation analysis - Healthy volunteer
* Diagnostic Test: Liquid biopsy for aberrant DNA methylation analysis - Benign lung disease


Participation Criteria
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Eligibility Criteria
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Indeterminate pulmonary nodule study cohort Inclusion criteria: Patients undergoing a biopsy of an indeterminate lung nodule by surgical excision, bronchoscopic biopsy or Interventional Radiology directed biopsy Exclusion criteria: No known concurrent cancer Known lung cancer for surgical resection study cohort Inclusion criteria: Patients with known non-small cell lung cancer who will have surgical resection for treatment Exclusion criteria: N/A Healthy volunteer cohort Inclusion criteria: Healthy persons Exclusion criteria: No known current cancer or history of cancer within 5 years Benign lung disease cohort Inclusion criteria: Patients with the following categories of benign lung disease: COPD/emphysema, Granulomatous infection, Interstitial lung disease including pulmonary fibrosis and interstitial lung disease. Exclusion criteria: N/A

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Indeterminate pulmonary nodule study cohort<br>Patients undergoing a biopsy of an indeterminate lung nodule by surgical excision, bronchoscopic biopsy or Interventional Radiology directed biopsy | Diagnostic Test: Liquid biopsy for aberrant DNA methylation analysis - Indeterminate pulmonary nodule<br>* 10 cc of blood is collected at one time point, which is prior to biopsy procedure<br>|
| Known lung cancer for surgical resection study cohort<br>Patients with known non-small cell lung cancer who will have surgical resection for treatment | Diagnostic Test: Liquid biopsy for aberrant DNA methylation analysis - Known lung cancer for surgical resection<br>* 10 cc of blood is collected at three time points: 1) before surgery; 2) 4-6 weeks post surgery; and 3) 6 months post surgery<br>|
| Healthy volunteer cohort<br>Healthy volunteers with a) no current diagnosis of cancer; b) no history of cancer over the last 5 years; and c) no existing known benign lung disease that is currently requiring treatment with medication. | Diagnostic Test: Liquid biopsy for aberrant DNA methylation analysis - Healthy volunteer<br>* 10 cc of blood is collected at one time point<br>|
| Benign lung disease cohort<br>Patients with the following categories of benign lung disease: COPD/emphysema Granulomatous infection Interstitial lung disease including pulmonary fibrosis and interstitial lung disease. | Diagnostic Test: Liquid biopsy for aberrant DNA methylation analysis - Benign lung disease<br>* 30 cc of blood is collected at one time point<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Indeterminate pulmonary nodule study cohort: Sensitivity and specificity of liquid biopsy test for malignancy | The patients with indeterminate nodules will be used to separately estimate the sensitivity (in those with lung cancer) and specificity (in those without lung cancer). At least 35 patients with lung cancer will provide an estimate of the standard error of the sensitivity < 0.09. Specificity will also be assessed in the normal controls (healthy volunteer cohort) using exact binomial confidence intervals. | 9 months | 
| Known lung cancer for surgical resection study cohort | To determine the correlation between the longitudinal marker levels and time to progression, to allow adjustment for relevant clinical characteristics. Correlations between change in the methylation results and response to therapy using radiographic findings (response, stable disease, progression) at 6 months post-baseline time point will be analyzed using a multinomial regression model. | 9 months | 
| Healthy volunteers study cohort | Specificity will be assessed in the normal controls (healthy volunteer cohort) using exact binomial confidence intervals. | 9 months | 
| Benign lung disease cohort | Thirty-five patients with benign lung disease will provide an estimate of the standard error of the specificity <0.09. Assuming a specificity value of 0.91 (32 negative/35 total), the exact 95% confidence interval is (0.77, 0.98). The specificity will be estimated separately, with an exact 95% confidence interval, for each of the benign lung disease subtypes as an exploratory analysis. | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung cancer, Biomarker, DNA methylation