Confocal Laser Endomicroscopy for Lung Cancer

No longer recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Must not be taking: Beta-blockers, Anticoagulants

Disqualifiers: Pregnancy, Hemodynamic instability, Hypoxemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding new imaging tools, such as nCLE (Needle-Based Confocal Laser Endomicroscopy, a light-based imaging method) and fluorescein (a dye that helps visualize tissues), to a common lung tissue sampling procedure (EBUS TBNA, Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration) improves lung cancer diagnosis. It compares the standard method with one that includes these advanced tools. Suitable candidates for this trial are individuals with suspected lung nodules between 8 mm and 30 mm in size, as indicated by a recent CT scan. As an unphased trial, this study provides an opportunity to contribute to innovative research that could enhance lung cancer diagnostic techniques.

Do I need to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking all current medications. However, you must not use beta-blockers within 24 hours before the procedure, and therapeutic anticoagulants must be held for an appropriate interval before the procedure. If you are undergoing chemotherapy, you cannot participate in the trial.

Will I have to stop taking my current medications?

The trial requires that you stop using beta-blockers 24 hours before the procedure and hold any therapeutic anticoagulants for an appropriate time before the procedure. If you are on these medications, you may need to stop them temporarily.

What prior data suggests that needle-based confocal laser endomicroscopy with fluorescein is safe for diagnosing lung cancer?

Studies have shown that needle-based confocal laser endomicroscopy (nCLE) with the dye fluorescein is safe for detecting lung cancer. Earlier research found nCLE both practical and safe, enabling doctors to view lung tissue images in real-time. Patients reported no major side effects during these studies. Fluorescein, the dye used for imaging, is commonly used in medical procedures and is generally well-tolerated. Overall, nCLE with fluorescein appears to be a safe method for diagnosing lung cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Confocal Laser Endomicroscopy (CLE) for lung cancer diagnosis because it offers a unique way to visualize tissue at a microscopic level in real-time. Unlike traditional methods, which rely on external imaging or tissue biopsies that are later analyzed in a lab, CLE allows doctors to see cellular details directly inside the lungs during the procedure. This technique can potentially lead to quicker, more accurate diagnoses without the need for multiple invasive procedures. Additionally, by combining CLE with techniques like Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS TBNA) and the use of fluorescein, researchers aim to enhance the precision of lung cancer detection, offering a more comprehensive view than standard options alone.

What evidence suggests that this trial's techniques could be effective for diagnosing lung cancer?

Research has shown that needle-based confocal laser endomicroscopy (nCLE) with fluorescein is highly effective in diagnosing lung cancer. One study correctly identified cancerous tissues 95.6% to 100% of the time using this method. Another study found that nCLE provided clear images in 92% of cases, which are crucial for accurate diagnosis. In this trial, some participants will undergo the usual EBUS TBNA procedure alone, while others will receive EBUS TBNA combined with nCLE and fluorescein. These findings suggest that adding nCLE and fluorescein may enhance lung cancer detection compared to EBUS TBNA alone. ^{3 4 6 7 8}

Who Is on the Research Team?

Sebastian Fernandez-Bussy, M.D.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for adults over 21 who suspect they have lung cancer with nodules sized between 8-30mm on a CT scan. They must understand and sign consent forms, not be pregnant or breastfeeding, and can't have used beta-blockers or certain anticoagulants recently. Those allergic to fluorescein or unable to tolerate general anesthesia are excluded.

Inclusion Criteria

I am 21 years old or older.

Ability to understand and willingness to sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) consent document

Possible peripheral polyneuropathy.

Exclusion Criteria

My lung lesions could not be found or confirmed during surgery.

You are allergic to fluorescein or have a high chance of having an allergic reaction.

You cannot handle the type of anesthesia used for surgery, according to the doctor who gives the anesthesia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo robotic EBUS TBNA, with some receiving nCLE and fluorescein IV

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and diagnostic performance

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Fluorescein
• Needle-Based Confocal Laser Endomicroscopy
• Ultrasound-Guided Transbronchial Needle Aspiration

Trial Overview The study tests if using needle-based confocal laser endomicroscopy (nCLE) with an imaging agent called fluorescein alongside standard EBUS TBNA improves lung cancer diagnosis in patients with peripheral pulmonary nodules compared to just EBUS TBNA.

How Is the Trial Designed?

Group I: Arm II (EBUS TBNA, nCLE, fluorescein) Experimental Treatment 3 Interventions

Patients undergo EBUS TBNA, nCLE, and receive fluorescein IV on study.

Group II: Arm I (EBUS TBNA) Active Control 1 Intervention

Patients undergo robotic EBUS TBNA on study.

Ultrasound-Guided Transbronchial Needle Aspiration is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as EBUS-TBNA for:

• Diagnosis and staging of lung cancer
• Evaluation of mediastinal lymph nodes

Approved in United States as EBUS-TBNA for:

• Diagnosis and staging of lung cancer
• Evaluation of mediastinal lymph nodes
• Detection of infections and inflammatory diseases

Approved in Canada as EBUS-TBNA for:

• Diagnosis and staging of lung cancer
• Evaluation of mediastinal lymph nodes

Approved in Japan as EBUS-TBNA for:

• Diagnosis and staging of lung cancer
• Evaluation of mediastinal lymph nodes

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study analyzing 5279 bronchoscopies, lung cancer (LC) was confirmed in 36.42% of patients, highlighting the effectiveness of bronchoscopy in diagnosing respiratory diseases.

The study found that different biopsy techniques have varying success rates: squamous cell lung cancer was diagnosed more frequently with endobronchial forceps biopsy, while adenocarcinoma and non-small cell lung cancer were more effectively diagnosed using EBUS-TBNA and EUS-FNA, indicating that the choice of technique should depend on the cancer type and location.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Observational cross-sectional study of 5279 bronchoscopy results for the practical effectiveness of various biopsy techniques in the diagnosis of lung diseases with particular emphasis on lung cancer. Błach, J., Frąk, M., Krawczyk, P., et al.[2022]

In a study of 15 lesions, EBUS-TBNA was successfully performed in 11 cases, demonstrating that the procedure is feasible in bronchi with a mean internal diameter of at least 4.5 mm.

No complications were reported during the procedure, indicating that EBUS-TBNA is a safe method for diagnosing lesions adjacent to narrow bronchi.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The usefulness of endobronchial ultrasonography-guided transbronchial needle aspiration at the lobar, segmental, or subsegmental bronchus smaller than a convex-type bronchoscope. Kurimoto, N., Inoue, T., Miyazawa, T., et al.[2022]

A total of 711 EBUS-TBNA procedures were analyzed, showing an increase in diagnostic quality from an initial 60.9% to 82.4% over the study period, highlighting the importance of continuous practice and evaluation in improving skills.

The introduction of rapid on-site cytological evaluation (ROSE) significantly enhanced the proportion of representative EBUS-TBNA results, with a high sensitivity of 94.9% for detecting malignancy, indicating its effectiveness as a diagnostic tool for lung cancer and mediastinal lymphadenopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Learning endobronchial ultrasound transbronchial needle aspiration - a 6-year experience at a single institution. Sørhaug, S., Hjelde, H., Hatlen, P., et al.[2018]

A 67-year-old man developed acute mediastinitis 13 days after undergoing EBUS-TBNA to diagnose an enlarged mediastinal lymph node, highlighting a rare but serious complication of the procedure.

Prompt treatment with antibiotics led to significant improvement in his symptoms and laboratory markers, emphasizing the importance of monitoring for complications after EBUS-TBNA, especially in cases involving necrotic lymph nodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A case of acute mediastinitis after endobronchial needle aspiration]. Kurimoto, N., Shinmyo, T., Tagay, R., et al.[2013]

Endobronchial ultrasound-guided transbronchial aspiration (EBUS-TBNA) demonstrated high diagnostic accuracy in non-small cell lung cancer (NSCLC) patients, with an overall sensitivity of 92.3% and specificity of 100% across 164 patients studied from 2007 to 2009.

The use of EBUS-TBNA not only effectively diagnosed and staged NSCLC but also allowed 54.7% of patients with confirmed malignancy to avoid unnecessary surgery, highlighting its role as a less invasive initial diagnostic tool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Roles of EBUS-TBNA in non-small cell lung cancer. Chung, FT., Kuo, CH., Chen, HC., et al.[2019]

Using a 19-G needle for EBUS-TBNA in 50 patients with suspected metastatic lung cancer resulted in a high success rate for testing molecular markers, with 90% success for PD-L1 and EGFR, and 86% for ALK, indicating its efficacy in obtaining sufficient tumor tissue.

The procedure was safe, with no adverse events reported, demonstrating that the larger needle size does not compromise patient safety while improving the quality and quantity of tissue samples for cancer diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study of the Performance of 19-G Needle in Endobronchial Ultrasound-guided Transbronchial Aspiration for the Diagnosis and Testing of Molecular Markers in Lung Cancer. Wahidi, MM., Davidson, K., Shofer, S., et al.[2023]

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a safe and effective procedure for diagnosing mediastinal and hilar lymphadenopathy, with a diagnostic yield of 79% across both malignant and benign conditions based on a study of 52 patients.

The procedure demonstrated high sensitivity (78.6%) and specificity (100%) for identifying lymph node abnormalities, making it a valuable tool for staging malignancies and diagnosing conditions like tuberculosis and sarcoidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility and safety of endobronchial ultrasound-guided transbronchial needle aspiration in patients with mediastinal and hilar lymphadenopathy: Western region experience. Aljohaney, AA.[2020]

In a study of 39 patients suspected of having lymphoma, the 19-gauge EBUS-TBNA needle demonstrated a sensitivity of 83% for detecting lymphoma, indicating it is an effective tool for diagnosis.

The overall sensitivity for definitive diagnosis of lymphoma using the 19G needle was 65%, which is comparable to the standard 22-gauge needle, but some patients still required further invasive procedures for accurate subtype characterization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic performance of 19-gauge endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in suspected lymphoma: A prospective cohort study. Lim, CE., Steinfort, DP., Irving, LB.[2021]

Both computer EBUS-TBNA simulation and wet lab simulation are effective for teaching basic EBUS-TBNA skills, with no significant differences in procedure time or successful biopsy rates between the two methods.

However, the computer simulation group was better at correctly identifying lymph nodes, while wet lab simulation increased learner confidence in using the actual EBUS-TBNA bronchoscope, suggesting that both methods provide valuable but different learning benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wet laboratory versus computer simulation for learning endobronchial ultrasound: a randomized trial. Stather, DR., MacEachern, P., Chee, A., et al.[2022]

Endobronchial ultrasound (EBUS) is a new, minimally invasive technique that allows pulmonologists to diagnose and stage lung cancer effectively by obtaining tissue samples through transbronchial needle aspiration (EBUS-TBNA).

This method is not only safe and simple but also offers a superior cost/benefit ratio compared to traditional diagnostic methods, making it an attractive option for lung cancer diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endobronchial ultrasound EBUS--a new method for the diagnosis and staging of lung cancer. Simon, M., Baldea, L., Pop, B., et al.[2015]

In a study of 6826 patients undergoing EBUS-TBNA, only 33 (0.48%) experienced infectious complications, primarily pneumonia and mediastinal infections, indicating that such complications are rare.

Risk factors for these infections included the presence of necrotic features in target lesions on CT scans and procedures performed via the esophagus, suggesting that careful evaluation of these factors is important for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectious complications of EBUS-TBNA: A nested case-control study using 10-year registry data. Kang, N., Shin, SH., Yoo, H., et al.[2021]

In a study of 1,317 patients undergoing EBUS-TBNA, complications occurred in only 1.44% of cases, indicating that the procedure is generally safe.

Transbronchial lung biopsy (TBBx) was identified as a significant risk factor for complications, with a higher incidence of complications in patients who underwent TBBx compared to those who did not. Additionally, the use of rapid on-site cytologic evaluation (ROSE) was associated with a reduced need for TBBx.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications, consequences, and practice patterns of endobronchial ultrasound-guided transbronchial needle aspiration: Results of the AQuIRE registry. Eapen, GA., Shah, AM., Lei, X., et al.[2022]

In a study of 370 patients undergoing EBUS-TBNA, the overall incidence of infectious complications was low at 4.05%, with a significantly higher rate (5.7%) in patients with risk factors compared to 0.8% in those without risk factors.

The study identified necrotic lesions as a specific risk factor for post-EBUS infections, suggesting that procedures involving these lesions should be approached with caution, although no fatalities occurred, indicating that EBUS-TBNA is generally a safe procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and Risk Factors for Infectious Complications of EBUS-TBNA: Prospective Multicenter Study. Serra Mitjà, P., Gonçalves Dos Santos Carvalho, F., Garcia Olivé, I., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39268137/

Assessment of needle-based confocal laser ... Conclusions: By retrospectively analyzing the nCLE lung cancer criteria published by Wijmans et al. in 2019, we observed 95.6% and 100% positive ...

2. thorax.bmj.com thorax.bmj.com/content/77/4/370

Bronchoscopic needle-based confocal laser endomicroscopy ... Results The nCLE imaging was performed in 26 patients. No adverse events occurred. In 24 patients (92%) good to high quality videos were obtained (final ...

3. jtd.amegroups.org jtd.amegroups.org/article/view/89316/html

Assessment of needle-based confocal laser endomicroscopy ... This study is the first to describe the association between nCLE technology and electromagnetic navigational bronchoscopy for lung nodule assessment.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06739421

The Diagnostic Value of Bronchoscopic Needle-based ... The goal of this prospective, multi-centre, randomised controlled clinical study is to evaluate the diagnostic efficacy and safety of nCLE guided lung biopsy in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11388227/

Assessment of needle-based confocal laser endomicroscopy ... This study is the first to describe the association between nCLE technology and electromagnetic navigational bronchoscopy for lung nodule assessment. • A ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34172559/

Bronchoscopic needle-based confocal laser ... Conclusion: Bronchoscopic nCLE imaging of peripheral lung lesions is feasible, safe and allows real-time lung cancer detection. Blinded raters ...

7. publications.ersnet.org publications.ersnet.org/content/erj/53/6/1801520

Needle-based confocal laser endomicroscopy for real-time ... Real-time lung cancer detection by endosonography-guided nCLE was feasible and safe. nCLE lung cancer characteristics were accurately recognised.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36535801/

Robotic bronchoscopic needle-based confocal laser ... We aim to assess feasibility, safety and needle repositioning based on real-time nCLE-guidance during robotic bronchoscopy in small peripheral lung nodules.