Molecular Analysis of Endoscopic Cytology Samples Supernatant in Pulmonary Nodules (KOBE)
Primary Purpose
Lung Cancer, Lung; Node
Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Blood samples
Sponsored by
About this trial
This is an interventional diagnostic trial for Lung Cancer focused on measuring Circulating free DNA, Methylation, Lung cancer, screening, lung nodule, radial EBUS, endobronchial ultrasound
Eligibility Criteria
Inclusion Criteria:
- rEBUS bronchoscopy planned for one, two or three ≤ 20 mm nodule
- World Health Organization (WHO) Performance status 0-3
- Informed signed consent
- Patient affiliated or beneficiary of a social security scheme (Social Security or Universal Medical Coverage).
Exclusion Criteria:
- Lung cancer diagnosed before the date of the procedure
- Lung cancer strongly suspected due to mediastinal or extra thoracic lesions
- Patient under State Medical Assistance
- Patient deprived of liberty on administrative or judicial decision, or patient under guardianship, curators or safeguard of justice
Sites / Locations
- Toulouse University HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
blood sampling
Arm Description
blood sample (2 tubes of 7.5 mL of blood = 15 mL) during the preoperative check-up on the day of the ultrasound-bronchoscopy in order to compare the sensitivity of the analysis of free circulating DNA present in the supernatant of pulmonary nodules less than 20 mm samples taken under ultrasound-bronchoscopy to that present in the plasma
Outcomes
Primary Outcome Measures
Sensitivity of targeted (9 genes panel) methylation analysis on supernatant cfDNA to detect a malignant nodule will be evaluated.
Promoter methylation rates of the 9 targeted genes in the free circulating DNA of the endoscopic samples supernatant is obtained by quantitative Polymerase Chain Reaction (PCR) of bisulfite-treated DNA fragments from the cytological samples supernatant after DNA concentration and separation by size at the Centre of Cancer Research of Toulouse (CRCT).
These analyses will be performed blinded to the clinical data and the histopathology result of the lung nodule.
Secondary Outcome Measures
Comparison of supernatant to pathology and plasma cfDNA methylation analysis. Specificity, negative predictive value (NPV), positive predictive value (PPV) of targeted (9 genes panel) methylation analysis on supernatant cfDNA to detect a malignant nodule
Methylation profiles of free circulating DNA from plasma obtained after centrifugation of blood samples will be obtained by the same method as described for analysis of cytopunction's supernatant methylation profile.
These analyses will be performed blinded to the clinical data and the histopathology result of the lung nodule.
Full Information
NCT ID
NCT05306912
First Posted
March 1, 2022
Last Updated
August 25, 2023
Sponsor
University Hospital, Toulouse
1. Study Identification
Unique Protocol Identification Number
NCT05306912
Brief Title
Molecular Analysis of Endoscopic Cytology Samples Supernatant in Pulmonary Nodules
Acronym
KOBE
Official Title
Molecular Analysis of Endoscopic Cytology Samples Supernatant in Pulmonary Nodules (Cancer Or Benign Endoscopy) (KOBE)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 8, 2022 (Actual)
Primary Completion Date
April 2024 (Anticipated)
Study Completion Date
April 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Toulouse
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Lung cancer screening is based on low dose CT scan (LDCT), a highly sensitive but poorly specific tool.
Complementary specific approaches are thus strongly needed, among which cell-free DNA (cfDNA) genotyping has been proven highly specific but of low sensitivity (25 to 50% for stage I diseases) due to inconstant tumor shed. Tumor biopsy is thus often required and radial endobronchial ultrasound (rEBUS) bronchoscopy is a minimally invasive approach (<3% complications) but of limited sensitivity in cases of nodules < 20 mm.
The investigators hypothesized that methylation analysis on cfDNA floating in supernatant derived from rEBUS specimens could improve rEBUS sensitivity
Detailed Description
Tumor biopsy is often required to characterize indeterminate nodules. Radial endobronchial ultrasound (rEBUS) bronchoscopy is often used due to a low rate of complications but its sensitivity is limited for small nodules.
The investigators hypothesized that methylation analysis on cfDNA floating in supernatant derived from rEBUS specimens could improve rEBUS sensitivity.
The primary outcome of this pilot, diagnostic validation, monocentric study is the sensitivity of targeted (9 genes panel) methylation analysis on supernatant cfDNA to detect a malignant nodule.
Secondary outcomes include the comparison of supernatant to pathology and plasma cfDNA methylation analysis.
Specificity, negative predictive value (NPV), positive predictive value (PPV) of targeted (9 genes panel) methylation analysis on supernatant cfDNA to detect a malignant nodule will be analyzed.
60 patients planned for a rEBUS bronchoscopy for one, two or three < 20 mm nodule, without mediastinal or extra thoracic lesions (cT1N0M0) will be included.
The day of the rEBUS bronchoscopy, 2 7.5 mL blood samples are collected. rEBUS samples' supernatant, usually discarded, is saved.
Cell free DNA is extracted from these biological specimens at the Laboratory of Oncological Medical Biology (LBMO) in Toulouse University Cancer Institute and tested for methylation (targeted analysis on 9 genes).
The patients will be followed for one year to obtain a final diagnosis and correlate it with tissue, nodule supernatant and plasma methylation analyses.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer, Lung; Node
Keywords
Circulating free DNA, Methylation, Lung cancer, screening, lung nodule, radial EBUS, endobronchial ultrasound
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
blood sampling
Arm Type
Experimental
Arm Description
blood sample (2 tubes of 7.5 mL of blood = 15 mL) during the preoperative check-up on the day of the ultrasound-bronchoscopy in order to compare the sensitivity of the analysis of free circulating DNA present in the supernatant of pulmonary nodules less than 20 mm samples taken under ultrasound-bronchoscopy to that present in the plasma
Intervention Type
Biological
Intervention Name(s)
Blood samples
Intervention Description
Patients will be taken from an additional blood sample (2 tubes of 7.5 mL of blood = 15 mL) during the preoperative check-up on the day of the ultrasound-bronchoscopy in order to compare the sensitivity of the analysis of free circulating DNA present in the supernatant of pulmonary nodules less than 20 mm samples taken under ultrasound-bronchoscopy to that present in the plasma.
Primary Outcome Measure Information:
Title
Sensitivity of targeted (9 genes panel) methylation analysis on supernatant cfDNA to detect a malignant nodule will be evaluated.
Description
Promoter methylation rates of the 9 targeted genes in the free circulating DNA of the endoscopic samples supernatant is obtained by quantitative Polymerase Chain Reaction (PCR) of bisulfite-treated DNA fragments from the cytological samples supernatant after DNA concentration and separation by size at the Centre of Cancer Research of Toulouse (CRCT).
These analyses will be performed blinded to the clinical data and the histopathology result of the lung nodule.
Time Frame
1st day (D0) of patients' inclusion, on morning of their ultrasound-bronchoscopy
Secondary Outcome Measure Information:
Title
Comparison of supernatant to pathology and plasma cfDNA methylation analysis. Specificity, negative predictive value (NPV), positive predictive value (PPV) of targeted (9 genes panel) methylation analysis on supernatant cfDNA to detect a malignant nodule
Description
Methylation profiles of free circulating DNA from plasma obtained after centrifugation of blood samples will be obtained by the same method as described for analysis of cytopunction's supernatant methylation profile.
These analyses will be performed blinded to the clinical data and the histopathology result of the lung nodule.
Time Frame
1st day (D0) of patients' inclusion, on morning of their ultrasound-bronchoscopy
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
rEBUS bronchoscopy planned for one, two or three ≤ 20 mm nodule
World Health Organization (WHO) Performance status 0-3
Informed signed consent
Patient affiliated or beneficiary of a social security scheme (Social Security or Universal Medical Coverage).
Exclusion Criteria:
Lung cancer diagnosed before the date of the procedure
Lung cancer strongly suspected due to mediastinal or extra thoracic lesions
Patient under State Medical Assistance
Patient deprived of liberty on administrative or judicial decision, or patient under guardianship, curators or safeguard of justice
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Valentin HELUAIN, MD
Phone
+33567771439
Ext
+33
Email
heluain.v@chu-toulouse.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Valentin HELUAIN, MD
Organizational Affiliation
University Hospital, Toulouse
Official's Role
Principal Investigator
Facility Information:
Facility Name
Toulouse University Hospital
City
Toulouse
State/Province
Occitanie
ZIP/Postal Code
31300
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sandra BERNARD, PM
Phone
+33561778573
Email
bernard.s@chu-toulouse.fr
First Name & Middle Initial & Last Name & Degree
Valentin HELUAIN
12. IPD Sharing Statement
Plan to Share IPD
No
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Molecular Analysis of Endoscopic Cytology Samples Supernatant in Pulmonary Nodules
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