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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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nCLE Guided Randomized Controlled Trial for Lung Cancer Diagnosis

Conditions
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Lung Carcinoma

Intervention / Treatment
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* Other: Fluorescein
* Device: Image-Guided Needle Confocal Laser Endomicroscopy
* Procedure: Ultrasound-Guided Transbronchial Needle Aspiration


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

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

What is the study measuring?
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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 |