Liquid Biopsy for Early Non-small Lung Cancer Detection

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Non Small-cell Lung Cancer
• Intervention / Treatment: 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

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 171

Contacts and Locations

• Study Contact: Name: Linda Garland, MD; Phone Number: 520-488-9503; Email: LGarland@uacc.arizona.edu

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients and volunteers will be recruited from the BUMC-T Pulmonary and UACC clinics (Indeterminate pulmonary nodule); through study posting on ClinicalTrials.gov and word of mouth (Healthy volunteers); UACC Thoracic Surgery Clinic (Pre-post lung cancer surgery); and Pulmonary Clinic (Benign Lung Disease).

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Indeterminate pulmonary nodule study cohort; 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; 10 cc of blood is collected at one time point, which is prior to biopsy procedure
Known lung cancer for surgical resection study cohort; 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; 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
Healthy volunteer cohort; 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; 10 cc of blood is collected at one time point
Benign lung disease cohort; 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; 30 cc of blood is collected at one time point

What is the study measuring?

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
Healthy volunteers study cohort	Specificity will 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
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

Collaborators and Investigators

• Sponsor: University of Arizona
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Linda Garland, MD, University of Arizona

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2022
• Primary Completion (Estimated): October 2, 2024
• Study Completion (Estimated): October 2, 2024

Study Registration Dates

• First Submitted: July 13, 2022
• First Submitted That Met QC Criteria: July 13, 2022
• First Posted (Actual): July 18, 2022

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Biomarker; Lung cancer; DNA methylation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: 2107020697; 1R43CA257133-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No