Confocal Laser Endomicroscopy for Lung Cancer

(CLEVER Trial)

Recruiting at 7 trial locations

Overseen By Jouke Annema, Prof. dr.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC)

Must not be taking: Anticoagulants, Chemotherapy

Disqualifiers: Pregnancy, Breastfeeding, Hypoxemia, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

208 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new imaging technique, needle-based confocal laser endomicroscopy (nCLE), can improve the accuracy of diagnosing potentially cancerous lung nodules. Participants will receive either a standard diagnostic test, conventional diagnostic bronchoscopy, or the same test with added nCLE imaging to determine if it eases diagnosis. This trial may suit individuals with suspected cancerous lung nodules that are difficult to access, typically located deep in the lungs. As an unphased trial, it offers participants the chance to contribute to innovative research that could enhance diagnostic methods for challenging lung conditions.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that therapeutic anticoagulant use must be withheld for an appropriate interval before the procedure. If you are undergoing chemotherapy, you may not be eligible to participate.

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

Research has shown that needle-based confocal laser endomicroscopy (nCLE) is safe for people. In one study, researchers used nCLE on 26 patients, and none experienced negative side effects. The video quality was good to high in 92% of cases. Another study confirmed that using nCLE during procedures to detect lung cancer is both feasible and safe. These findings suggest that incorporating nCLE into lung examinations is well-tolerated and poses minimal risk to participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using confocal laser endomicroscopy (nCLE) in diagnosing lung cancer because it offers real-time, high-resolution imaging of lung tissue at the cellular level. Unlike traditional diagnostic methods, which rely mainly on visual observation and biopsies, nCLE allows doctors to see detailed images of the tissue during the bronchoscopy procedure itself. This technique could lead to more accurate and immediate identification of cancerous cells, potentially reducing the need for multiple procedures and speeding up diagnosis.

What evidence suggests that needle-based confocal laser endomicroscopy is effective for improving diagnostic yield in lung cancer?

Research has shown that needle-based confocal laser endomicroscopy (nCLE) could enhance lung cancer diagnosis. In this trial, participants in the nCLE arm will undergo diagnostic bronchoscopy with nCLE. One study showed that nCLE correctly identified lung cancer in 95.6% of cases, with some cases reaching 100% accuracy. Another study found that nCLE produced clear images in 92% of patients, aiding doctors in making better decisions when examining lung nodules. This technology guides the needle to the right spot, potentially leading to more accurate tissue samples and fewer errors. Overall, nCLE appears promising for improving the accuracy of lung cancer diagnoses during lung examinations. ^{4 5 6 7}

Who Is on the Research Team?

Jouke Annema, Prof. dr.

Principal Investigator

Amsterdam UMC

Are You a Good Fit for This Trial?

This trial is for adults over 18 with suspected malignant lung lesions suitable for bronchoscopic diagnosis. The lesion must be solid, larger than 10mm but not exceeding 30mm, and accessible by conventional bronchoscopy as indicated by a CT scan. Participants must understand and consent to the study.

Inclusion Criteria

If the pre-procedural CT-scan does not reveal an airway leading to the target lesion, there is a low likelihood of successful access with a conventional bronchoscope and study participation would be declined.

I am suspected to have lung cancer and need a lung biopsy.

The solid component of any lesions must be larger than 10 millimetres.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Procedure

Participants undergo diagnostic bronchoscopy with or without nCLE imaging

During procedure

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the bronchoscopy procedure

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Conventional diagnostic bronchoscopy
• Neelde Based Confocal Laser Endomicroscopy

Trial Overview The trial tests if adding needle-based confocal laser endomicroscopy (nCLE) to regular diagnostic bronchoscopy improves the chances of correctly diagnosing lung cancer in patients with peripheral pulmonary nodules.

How Is the Trial Designed?

Group I: nCLE arm Experimental Treatment 2 Interventions

Diagnostic bronchoscopy is done according to institutional practice with the addition of nCLE

Group II: Control arm Active Control 1 Intervention

Diagnostic bronchoscopy is done according to institutional practice without the addition of nCLE

Conventional diagnostic bronchoscopy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Diagnostic Bronchoscopy for:

• Diagnosis of lung diseases
• Evaluation of lung lesions
• Sampling of lung tissue

Approved in United States as Diagnostic Bronchoscopy for:

• Diagnosis of lung diseases
• Evaluation of lung lesions
• Sampling of lung tissue

Approved in Canada as Diagnostic Bronchoscopy for:

• Diagnosis of lung diseases
• Evaluation of lung lesions
• Sampling of lung tissue

Approved in Japan as Diagnostic Bronchoscopy for:

• Diagnosis of lung diseases
• Evaluation of lung lesions
• Sampling of lung tissue

Approved in China as Diagnostic Bronchoscopy for:

• Diagnosis of lung diseases
• Evaluation of lung lesions
• Sampling of lung tissue

Approved in Switzerland as Diagnostic Bronchoscopy for:

• Diagnosis of lung diseases
• Evaluation of lung lesions
• Sampling of lung tissue

Who Is Running the Clinical Trial?

Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC)

Lead Sponsor

Trials

17

Recruited

7,800+

Mauna Kea Technologies

Industry Sponsor

Trials

20

Recruited

1,800+

Published Research Related to This Trial

In a 15-month study of 697 patients undergoing advanced diagnostic bronchoscopy, severe complications were rare, occurring in only 2.4% of patients, but they had serious consequences, including unplanned hospital visits and deaths.

Many complications occurred days or weeks after the procedure, highlighting the need for proactive monitoring to identify and manage these delayed adverse events effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thirty-Day Complications, Unplanned Hospital Encounters, and Mortality after Endosonography and/or Guided Bronchoscopy: A Prospective Study. Magnini, D., Sotgiu, G., Bello, G., et al.[2023]

In a study of 362 patients with visible endobronchial tumors, pre-biopsy bronchial brushing significantly improved the diagnostic yield for lung cancer compared to post-biopsy brushing, with yields of 49.2% versus 31.8% respectively.

The study found no significant difference in the occurrence of treated bleeding between pre- and post-biopsy brushing, indicating that the technique is safe while enhancing diagnostic effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The optimal sequence for bronchial brushing and forceps biopsy in lung cancer diagnosis: a random control study. Hou, G., Miao, Y., Hu, XJ., et al.[2020]

Recent advancements in bronchoscopy technology enhance the ability to perform minimally invasive evaluations and a variety of interventions in the tracheobronchial tree, improving diagnostic and therapeutic outcomes.

There is a critical need for well-designed studies to establish guidelines for the effective use of new bronchoscopic techniques in clinical practice, addressing their limitations and cost-effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flexible bronchoscopy and its role in the staging of non-small cell lung cancer. Herth, FJ., Eberhardt, R.[2010]

In a study of 259 lung transplant recipients undergoing flexible fiberoptic bronchoscopy, complications occurred in only 0.7% of procedures, indicating that bronchoscopy is generally safe for these patients.

The involvement of trainees in bronchoscopies did not significantly increase the rate of complications, suggesting that trainee participation is safe and does not adversely affect patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An analysis of potential risk factors for early complications from fiberoptic bronchoscopy in lung transplant recipients. Smith, L., Singer, JP., Hayes, M., et al.[2012]

Surgical resection remains the only curative option for lung cancer, with the five-year survival rate significantly improving when tumors are detected early.

Bronchoscopy is crucial for both diagnosing and treating lung cancer, helping to identify tumors and manage symptoms like bleeding and difficulty breathing through various therapeutic techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lung Cancer: A Bronchoscopic Approach. Strausz, J.[2019]

Flexible bronchoscopy has a high diagnostic yield of 88% for detecting endoscopically visible lung malignancies, significantly improved by using cytological techniques like bronchial washings and brushings in addition to biopsies.

Cytological sampling techniques increased the diagnostic yield from 77% with biopsies alone to 88% overall, and repeat bronchoscopies after non-diagnostic results were successful in 9 out of 11 cases, indicating their importance in diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bronchoscopic diagnosis of endoscopically visible lung malignancies: should cytological examinations be carried out routinely? Dobler, CC., Crawford, AB.[2010]

Confocal laser endomicroscopy is a feasible imaging technique for lepidic adenocarcinomas, which are a type of lung cancer.

This imaging method could potentially enhance the effectiveness of virtual electromagnetic navigation bronchoscopy for identifying ground-glass opacities in real-time, suggesting a promising direction for future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Confocal laser endomicroscopy to guide sampling of a pure ground-glass opacity. Viatgé, T., Villeneuve, T., D'Aure, D., et al.[2021]

Needle-based confocal laser endomicroscopy (nCLE) is a safe and feasible method for real-time imaging of suspected peripheral lung cancer, with no adverse events reported in a study of 26 patients.

The nCLE imaging successfully detected malignancy in 22 out of 23 lung cancer cases, and blinded raters achieved 95% accuracy in distinguishing cancerous tissue from normal lung parenchyma, indicating its potential as a valuable tool for bronchoscopic guidance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bronchoscopic needle-based confocal laser endomicroscopy (nCLE) as a real-time detection tool for peripheral lung cancer. Kramer, T., Wijmans, L., de Bruin, M., et al.[2022]

In a study of 1,100 interventional pulmonology procedures, trainee involvement was linked to longer procedure times (average of 50.81 minutes compared to 32.49 minutes) and increased sedation requirements, indicating a potential impact on efficiency.

The presence of trainees also correlated with a higher complication rate (4.5% with trainees vs. 1.2% without), suggesting that while training is essential, it may pose additional risks to patients during procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trainee impact on procedural complications: an analysis of 967 consecutive flexible bronchoscopy procedures in an interventional pulmonology practice. Stather, DR., MacEachern, P., Chee, A., et al.[2022]

Flexible bronchoscopy is a crucial diagnostic tool in respiratory medicine, but it carries a range of potential complications due to its invasive nature.

To minimize risks associated with flexible bronchoscopy, it is essential to have a skilled team, close monitoring, and immediate access to resuscitation facilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Successful risk management in flexible bronchoscopy]. Darwiche, K., Hecker, E., Volmerig, J., et al.[2009]

Confocal laser endomicroscopy is a cutting-edge endoscopic technique that allows for real-time histological diagnosis of gastrointestinal diseases, enhancing the accuracy of detecting conditions like gastrointestinal neoplasia.

This technique is particularly valuable for screening and monitoring gastrointestinal neoplasia, potentially improving patient outcomes through earlier and more precise diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Confocal laser endomicroscopy of the upper digestive tract: history of development and screening]. Sukhikh, MV., Panchenkov, DN.[2020]

Confocal laser endomicroscopy, using acriflavine hydrochloride, allows for high-quality imaging of living lung cells during bronchoscopy, with no reported side effects, making it a safe diagnostic tool.

This technique demonstrated high accuracy in detecting neoplastic changes, with a sensitivity of 96.0% and specificity of 87.1%, potentially enabling rapid diagnosis of lung cancer during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Confocal laser endomicroscopy for diagnosing lung cancer in vivo. Fuchs, FS., Zirlik, S., Hildner, K., et al.[2013]

Robotic bronchoscopy has improved navigational success for diagnosing small lung nodules, but challenges remain due to the risk of missing the target nodule.

The introduction of needle-based confocal laser endomicroscopy allows for real-time visualization of cells during robotic bronchoscopy, potentially enhancing the accuracy of diagnosing small lung nodules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robotic Navigational Bronchoscopy Combined with Needle-Based Confocal Laser Endomicroscopy: Case Report of a Novel Approach to Diagnose Small Lung Nodules. Manley, C., Kramer, T., Kumar, R., et al.[2022]

In a study involving 159 asthmatic patients who underwent 273 bronchoscopies, the procedures were found to be generally safe, with adverse events occurring in only 34 instances, none of which followed allergen challenges.

Most complications were associated with the combination of endobronchial biopsy and bronchoalveolar lavage, indicating that bronchoalveolar lavage may be responsible for the majority of adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of research bronchoscopy, biopsy and bronchoalveolar lavage in asthma. Elston, WJ., Whittaker, AJ., Khan, LN., et al.[2013]

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

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

6. 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.

7. 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.