Needle-Based Confocal Laser Endomicroscopy for Diagnosis of Lung Cancer in Patients With Peripheral Pulmonary Nodules

nCLE Guided Randomized Controlled Trial for Lung Cancer Diagnosis

This clinical trial compares the addition of needle-based confocal laser endomicroscopy (nCLE) and fluorescein to endobronchial ultrasound-guided transbronchial needle aspiration (EBUS TBNA) with EBUS TBNA alone for the diagnosis of lung cancer in patients with peripheral pulmonary nodules. EBUS TBNA is a diagnostic procedure that can be used to sample lung tissue. nCLE is a novel high-resolution imaging technique that uses a laser light to create real-time microscopic images of tissues. It can be integrated into needles allowing real-time cancer detection during endoscopy. Fluorescein is an imaging agent that can be used to visualize tissue. Using nCLE and fluorescein in combination with EBUS TBNA may be more effective in diagnosing lung cancer than using EBUS TBNA alone.

Study Overview

• Status: Recruiting
• Conditions: Lung Carcinoma
• Intervention / Treatment: Procedure: Ultrasound-Guided Transbronchial Needle Aspiration; Other: Fluorescein; Device: Image-Guided Needle Confocal Laser Endomicroscopy

Detailed Description

PRIMARY OBJECTIVE:

I. To compare the first-pass diagnostic yield of the sequential needle passes (rapid on-site evaluation [ROSE]) between the robotic-nCLE-TBNA arm and the robotic-guided arm in peripheral pulmonary nodule (PPNs).

SECONDARY OBJECTIVES:

I. To compare the per-patient diagnostic yield (cumulative pass diagnostic yield: cumulative number of passes until five cumulated passes) of robotic-nCLE-guided TBNA to that of robotic-guided TBNA in PPNs.

II. To compare the proportion of patients with lung cancer treatment in the robotic-nCLE-guided TBNA arm to that of the robotic-guided TBNA arm in PPNs.

III. To compare the proportion of patients with follow-up (video-assisted thoracoscopic surgery [VATS]) or transthoracic needle aspiration (TTNA) or TBNA procedures in the robotic-nCLE-guided TBNA arm to that of the robotic-guided TBNA arm in PPNs.

IV. To compare the number of passes needed to obtain a final diagnosis of robotic-nCLE-guided TBNA to that of robotic-guided TBNA in PPNs.

V. To assess the diagnostic performance (sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV], accuracy) of the sequential cumulative nCLE passes and the sequential cumulative ROSE passes using the final diagnosis as a reference.

VI. To assess the feasibility by obtaining adequate confocal laser endomicroscopy (CLE) video footage in > 80% of the PPN punctures.

VII. To assess the safety of nCLE imaging, as defined by:

VIIa. The number and frequency of all adverse events (AE)/serious adverse events (SAE) from the start of the procedure until end of 12-month follow-up; VIIb. The number and frequency of nCLE procedure-related AE/SAE from the start of the procedure until end of 12-month follow-up.

VIII. To assess the reproducibility of nCLE criteria to the reference standard. Three nCLE characteristics for the detection of malignancy were identified during Wijmans et al. study:

VIIIa. Dark enlarged pleomorphic cells; VIIIb. Dark cell clusters consist of overlapping cell structures ('dark clumps') and; VIIIc. Continuous movement of the cells in one direction ('directional streaming').

IX. To create an nCLE image atlas for malignant characteristics in PPNs.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo robotic EBUS TBNA on study.

ARM II: Patients undergo EBUS TBNA, nCLE, and receive fluorescein intravenously (IV) on study.

• Study Type: Interventional
• Enrollment (Estimated): 118
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Recruiting
      • Mayo Clinic in Florida
      • Contact: Clinical Trial Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Sebastian Fernandez-Bussy, M.D.
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Not yet recruiting
      • Mayo Clinic in Rochester
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Janani S. Reisenauer, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• >= 21 years of age
• Suspected PPN
• Nodule size in computed tomography (CT) between 8 mm and 30 mm (largest dimension)
• Ability to understand and willingness to sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) consent document

Exclusion Criteria:

• Inability or non-willingness to provide informed consent
• Failure to comply with the study protocol
• Patients with known allergy for fluorescein or risk factors for an allergic reaction
• Use of beta-blocker within 24 hours before the start of the bronchoscopic procedure
• Possibly pregnant, pregnant or breastfeeding women
• Patients with hemodynamic instability
• Patients with refractory hypoxemia
• Patients with a therapeutic anticoagulant that cannot be held for an appropriate interval before the procedure
• Patients who are unable to tolerate general anesthesia according to the anesthesiologist
• Patient undergoing chemotherapy
• INTRA-OPERATIVE EXCLUSION/STOPPING CRITERIA:
• The lesions are unable to be localized/confirmed by bronchoscopy
• The procedure will be terminated if the patient develops a significant procedural complication as determined by the treating physician
• The procedure will be terminated if the patient develops hemodynamic instability as determined by the treating physician

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (EBUS TBNA); Patients undergo robotic EBUS TBNA on study.	Procedure: Ultrasound-Guided Transbronchial Needle Aspiration; Undergo EBUS TBNA; Other Names: EBUS-TBNA; Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration
Experimental: Arm II (EBUS TBNA, nCLE, fluorescein); Patients undergo EBUS TBNA, nCLE, and receive fluorescein IV on study.	Procedure: Ultrasound-Guided Transbronchial Needle Aspiration; Undergo EBUS TBNA; Other Names: EBUS-TBNA; Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration; Other: Fluorescein; Given IV; Device: Image-Guided Needle Confocal Laser Endomicroscopy; Undergo nCLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
First-pass diagnostic yield	Calculated as the proportion of patients for which first-pass transbronchial needle aspiration during bronchoscopic procedure yielded a definitive diagnosis out of the total number of patients that have received a diagnostic procedure.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Per-patient diagnostic yield	Calculated as the proportion of patients in whom the bronchoscopic procedure yielded a definitive diagnosis out of the total number of patients that have received a diagnostic procedure. Per patient diagnostic yield of each bronchoscopic procedure will be calculated, and the accuracy of each technique using the final/definitive diagnosis as the reference. The diagnostic yield and accuracy for each method will be compared.	Up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical impact of needle-based confocal laser endomicroscopy (nCLE)	Assessed by determining the proportion of patients with a correct change in definitive diagnosis and the associated change in management plan with nCLE. Overall diagnostic and therapeutic management proportion differences in the two arms will be compared using a chi-square test. Differences between the two arms regarding the specific diagnostic and therapeutic management categories will be compared using McNemar's test.	Up to 2 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Sebastian Fernandez-Bussy, M.D., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2023
• Primary Completion (Estimated): May 23, 2025
• Study Completion (Estimated): May 23, 2025

Study Registration Dates

• First Submitted: September 23, 2022
• First Submitted That Met QC Criteria: September 23, 2022
• First Posted (Actual): September 27, 2022

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: MKT_2021_lung_01 (Mayo Clinic in Florida); NCI-2022-07660 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 21-008276 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No