Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Carcinoma

Lung Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

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

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

Confocal microscopy through the TBNA needle before tissue sampling using the Cellvizio system and AQ flex probe (Mauna Kea Technologies)

Neelde Based Confocal Laser Endomicroscopy

Conventional diagnostic bronchoscopy with r-EBUS and optionally fluoroscopy AND/OR EMN AND/OR VB AND/OR ultrathin scope

Conventional diagnostic bronchoscopy

Saskia van Heumen, MSc

Jouke Annema, Prof. dr.

Ali Sadoughi, MD, DAABIP

Daniela Gompelmann, Prof.

Daniela Gompelmann

Christina Bal

Jirí Votruba

Zuzana Šestáková

Grigoris Stratakos, MD, PhD

Nektarios Anagnostopoulos

Evangelia Koukaki

Grigoris Stratakos

Katerina Bakiri

Venerino Poletti, Prof.

Claudia Ravaglia

Venerino Poletti, MD, PhD

Jouke Annema

Saskia van Heumen

Peter Bonta

Johannes Daniels

Marjolein Heuvelmans

Jürgen Hetzel, Prof.

Jürgen Hetzel

Maik Haentschel

The goal of this multi-center randomized clinical trial is to evaluate the added value of needle based confocal laser endomicroscopy (nCLE)-imaging to regular diagnostic bronchoscopic peripheral lung lesion analysis on the diagnostic yield in patients with peripheral pulmonary nodules suspect for malignancy.

The main question\[s\] it aims to answer are:

To determine if the addition of nCLE-imaging to conventional diagnostic bronchoscopic peripheral lung lesion analysis results in an improved diagnostic yield (defined as the proportion of patients in whom the bronchoscopic procedure results in a definitive diagnosis out of the total number of patients that have received the diagnostic bronchoscopic procedure).

Participants will undergo diagnostic bronchoscopy either with or without the addition of nCLE imaging before each TBNA. Based on the feedback of the CLE images on (in)correct placement of the needle, the needle might be repositioned before sampling. Comparison between the diagnostic yield of these groups will be done including subgroup analysis.

Rationale: Lung cancer screening and the increasing use of chest-computed tomography (CT) has led to an increase in the number of (incidental) found suspected malignant lung lesions. Since tissue acquisition for pathological analysis is prerequisite for diagnosis and optimal treatment, a drastic increase in the number of patients that need to undergo bronchoscopy is expected.

Over 70% of the suspected lesions develop in the periphery of the lung and are therefore not visible during conventional bronchoscopy. Although several bronchoscopic navigational techniques demonstrated an improved navigation towards the target lesion, the diagnostic yield remains suboptimal due to a substantial near-miss rate. As a result, the need for complementary bronchoscopic guidance that provides real-time feedback on the correct positioning of the biopsy instruments is urgent.

Needle-based Confocal laser endomicroscopy (nCLE) is a novel high-resolution imaging technique that uses an excitation laser light to create 'real-time' microscopic images of tissues. nCLE can be integrated into the biopsy needle, allowing real-time cancer detection at the tip of the biopsy needle during bronchoscopy. The confocal microscope captures autofluorescence of tissues or, combined with intravenously (IV) infused fluorophores (such as fluorescein) allows imaging of individual tumor cells. Recent studies on nCLE-imaging in lung tumors and metastatic lymph nodes have identified and validated nCLE criteria for malignancy (enlarged pleomorphic cells, dark clumps and directional streaming) and airway/lung parenchyma (alveoli, elastin fibres of the conducting airway, bronchial epithelium and still image) and granulomas. A recent study demonstrated that these nCLE-criteria can be used in real-time to fine-tune the needle positioning during ongoing bronchoscopy and thereby potentially improve the diagnostic yield.

This randomized controlled trials aims to evaluate the added value of nCLE-imaging (smart needle) to the conventional used bronchoscopic approach for peripheral lung lesion analysis.

Objective: This multicenter, randomized controlled trial, aims to investigate if nCLE-imaging integrated with conventional bronchoscopy results in a higher diagnostic yield compared to conventional bronchoscopy without nCLE in the diagnosis of peripheral lung nodules.

Study design: Investigator-initiated, international, multi-center randomized controlled trial including university and general hospitals.

Study population: Patients (\>18 years old) with suspected malignant peripheral lung lesions with an indication for bronchoscopic analysis.

Procedure: Bronchoscopy will be performed according to institutional practice, including radial endobronchial ultrasound (r-EBUS) and optionally fluoroscopy, electromagnetic navigation, virtual bronchoscopy and/or ultrathin bronchoscopy. This is followed by transbronchial needle aspiration (TBNA) and (cryo-)biopsies (control arm). In the study arm, nCLE-imaging will be added prior to TBNA tissue acquisition to fine-tune the sampling area. Cytology staining for rapid onsite evaluation (ROSE) and cellblock will be performed according to local practice.

Primary objective:

To determine if the addition of nCLE-imaging to conventional bronchoscopic peripheral lung lesion analysis results in an improved diagnostic yield. (defined as the proportion of patients in whom the bronchoscopic procedure results in a definitive diagnosis out of the total number of patients that have received the diagnostic bronchoscopic procedure).

Confocal Laser Endomicroscopy VERification

Bronchoscopy With and Without Needle-based Confocal Laser Endomicroscopy for Peripheral Lung Nodule Diagnosis: Protocol for a Multicenter Randomized Controlled Trial (CLEVER Trial)

All data relevant to the study will be included in the article or uploaded as supplementary information. Data requests can be submitted to the researchers at the Amsterdam UMC, Amsterdam, The Netherlands.

Diagnostic yield (defined as the proportion of patients in whom the bronchoscopic procedure results in a definitive diagnosis \[either malignant, specific benign or non-specific benign confirmed as benign in follow-up\], relative to the total number of patients that underwent the diagnostic bronchoscopic procedure). If patients with multiple lesions are included, the diagnostic yield will be computed per nodule.

Diagnostic sensitivity for malignancy (defined as the proportion of patients in whom the bronchoscopic procedure diagnoses malignancy relative to the total number of patients with a final diagnosis of malignancy as determined by the reference standard).

Diagnostic yield according to the strict definition by Vachani et al.(21) (defined as the proportion of patients in whom the bronchoscopic procedure results in a definitive diagnosis \[either malignant or specific benign diagnosis\], relative to the total number of patients that underwent the diagnostic bronchoscopic procedure).

Procedure duration (from bronchoscope insertion until removal).

Percentage of patients in which the needle was fine-tuned (defined as moving the needle within the same distal airway) or repositioned (defined as the selection of a different distal airway for tissue sampling) based on nCLE feedback (defined as the number of patients the needle was fine-tuned/repositioned divided by the total number of patients in which nCLE imaging was used).

Diagnostic yield of ROSE (defined as the proportion of patients in whom ROSE resulted in a classifying diagnosis \[malignant or specific benign diagnosis\], relative to the total number of patients).

Proportion of patients in which ROSE provided tool-in-lesion confirmation, meaning that the acquired tissue shows signs of a malignant or non-malignant diagnosis and was not related to airway/lung parenchyma sampling such as bronchus epithelium/blood contamination, and tissue not suitable for a specific diagnosis such as atypical cells.

Complication rate (defined as any complication or complication categories occurring during or directly after the bronchoscopic procedure or any procedure-related complication within one week after the procedure).

Requirement of additional diagnostic procedures (CT-guided transthoracic biopsies, surgical diagnostics and/or additional bronchoscopy) during the 6-month follow-up period.

To assess the diagnostic yield (primary outcome) for two subgroups (≤20 mm vs \>20 mm)

To assess the diagnostic yield (primary outcome) for three subgroups (eccentric vs concentric vs absent)

To assess the diagnostic yield (primary outcome) for three subgroups (upper lobe (without lingual) vs middle lobe/lingual vs lower lobe)

To assess the diagnostic yield (primary outcome) for three subgroups (Brock score \<10%, 10 - 35%, 36-70% and \>70%)

Mauna Kea Technologies

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

Prof. dr. J.T. Annema

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Urinary Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Administration of fluorescein, intravesically and intravenously. CLE measurements with flexible and rigid probe of papillary bladder tumour and rigid probe-measurement of resection bed.

Confocal Laser Endomicroscopy (CLE)

J. R. Oddens, MD, PhD

A prospective monocenter diagnostic accuracy study of Confocal Laser Endomicroscopy (CLE) for Bladder Cancer(BC) to assess two primary objectives:

1. The diagnostic accuracy of flexible probe-based confocal laser endomicroscopy (CLE) compared to histopathology of the resection specimen.
2. The diagnostic accuracy of CLE-based assessment of the surgical radicality of the resection bed (radical vs irradical) in comparison with histopathology of a biopsy of the resection bed.

All patients with a papillary bladder tumor on cystoscopy will be included in this trial.

Rationale:

Initial evaluation of gross hematuria consists of White Light Cystoscopy (WLC). Urine cytology combined with contrast imaging of the upper urothelial tract is performed when a bladder tumor is seen. Follow up of non-muscle invasive bladder carcinoma (NMIBC) after initial treatment consists of similar steps. When a suspected lesion is visualized, a transurethral resection of the bladder tumor (TURBT) is performed for therapeutic and diagnostic purposes. TURBT is considered to be the gold standard for diagnosis of urothelial carcinoma of the bladder (UCB). High recurrence rates of UCB after TURBT are reported, leading to repetitive surgery and high costs. In certain cases of high grade UCB a second look TURBT has proven to be beneficial after primary resection to ensure radical resection. Furthermore, recent research suggests that active surveillance for low-grade bladder tumors is safe. Confocal laser endomicroscopy (CLE), a high resolution optical imaging technique that can be used in combination with endo-urological procedures, seems promising to improve diagnosis of urothelial cancer, possibly without the need for immediate transurethral resection to obtain histological confirmation. CLE characteristics of UCB have been determined and validated using rigid probes, which are incompatible with flexible cystoscopes used for outpatient cystoscopies. With the present study, we aim to assess the diagnostic value of flexible probe based CLE for diagnosis and grading of UCB. Furthermore to possibly prevent second look TURBT in the future,an assessment of CLE features of the resection bed using a rigid CLE-probe will be performed.

Objective:

Primary objectives:

This study is two-fold and, therefore, has two primary objectives:

1. Investigating the diagnostic accuracy of CLE (Cystoflex™F probe) during flexible cystoscopy for diagnosis and grading of urothelial carcinoma of the bladder.
2. To investigate the diagnostic potential of CLE (Cystoflex™ UHD-R probe) for the assessment of the surgical radicality after transurethral resection of a bladder tumor (after TURBT)

Secondary objective:

- To construct a convolutional neural network for computer aided assessment of CLE images for diagnosis and grading of UCB.

Study design:

This is a prospective monocenter, observational diagnostic accuracy study. Diagnostic accuracy study to compare the CLE-based diagnosis with the histopathologic findings.

Study population: All patients \>18 years old with a papillary bladder tumor who are planned for TURBT are eligible for this study. We will include 60 patients in this pilot study.

Intervention: At the operation theatre, before performing a TURBT for the standard clinical care, we introduce a flexible cystoscope to map the bladder, then we record CLE images of the index lesion using the Cystoflex™F. Subsequently, we replace the flexible scope by the (rigid) resectoscope. We acquire additional images with the Cystoflex™ UHD-R rigid probe. We perform the TURBT. After completion of the TURBT, we introduce the Cystoflex™ UHD-R probe again for imaging of the resection bed. At a later stage correlation with a standard biopsy of the resection bed will be performed.

For CLE imaging, a fluorescent contrast agent (fluorescein) will be used intravesically and intravenously, respectively, to temporarily stain the extracellular matrix of the urothelium. We will introduce fluorescein for intravesical use through a bladder catheter and rinse the fluorescein out of the bladder after an indwelling time of 5-10 minutes. Before CLE measurement of the resection bed we will administer fluorescein intravenously.

Main study parameters/endpoints:

1. Overall accuracy, sensitivity and specificity of flexible probe CLE-based diagnosis (benign vs malignant) and grading (low-grade versus high-grade) in comparison with the histopathology of the resection specimen.
2. Overall accuracy, sensitivity and specificity of CLE-based assessment of the surgical radicality of the resection bed (radical versus irradical) in comparison with the histopathology of the biopsy of the resection bed.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participants will not benefit directly from this study. We hypothesize, however, that the results of this study will contribute to improvements in the diagnostic and surgical procedure for UCB. Outpatient-based cystoscopy with the potential diagnostic certainty of CLE-based grade assessment may enable active surveillance in low-risk UCB, and thus may even lead to a reduction in surgical procedures. We will introduce a CLE probe before TURBT via the working channel of the flexible cystoscope and hold it in direct contact with the bladder tumor to obtain CLE images. Before image acquisition of the bladder tumor we administer fluorescein intravesical, which is a fluorescent dye, used regularly intravenously in ophthalmatology. Before image acquisition of the resection bed we administer fluorescein intravenously. In patients not known with an allergy to this dye, this is a safe procedure. Patients with a known allergic reaction to fluorescein cannot participate in this study. Patients will be exposed to approximately 20 minutes of extra surgery time and the introduction of a flexible cystoscope compared to regular TURBT. As a result there is little burden to study participation for the patients. Adverse events are not expected based on previous experiences. The hospital's internal protocol for standard clinical care and histopathologic evaluation are not going to be affected by the study protocol.

Confocal Laser Endomicroscopy During TransUrethral Resection for Improving BC Diagnosis and Treatment

Confocal Laser Endomicroscopy During TransUrethral Resection for Improving Bladder Cancer Diagnosis and Treatment

Diagnostic accuracy (sensitivity, specificity, negative predictive value and positive predictive value) of flexible probe based CLE for the diagnosis (low-grade malignant, high-grade malignant) of urothelial carcinoma of the bladder.

To investigate the diagnostic potential of CLE for the assessment of the surgical radicality (residual tumor/no residual tumor) after TURBT.

To investigate the diagnostic potential of CLE for depth of resection (according to the tissue in the resection margin: urothelium, submucosa, m. detrusor or perivesical fatty tissue) after TURBT.

To construct a convolutional neural network for computer aided assessment of pCLE images for diagnosis and grading of UCB.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Confocal Laser Endomicroscopy VERification	NCT06079970	Lung Cancer Lung Neoplasm M... Carcinoma, Non-... Neoplasm of Lun...	Neelde Based Co... Conventional di...	18 Years -	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Confocal Laser Endomicroscopy During TransUrethral Resection for Improving BC Diagnosis and Treatment	NCT05273593	Bladder Cancer CLE	Confocal Laser ...	18 Years -	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Confocal Laser Endomicroscopy VERification	NCT06079970	Lung Cancer Lung Neoplasm M... Carcinoma, Non-... Neoplasm of Lun...	Neelde Based Co... Conventional di...	18 Years -	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Spots Global Cancer Trial Database for cle

Every month we try and update this database with for cle cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for cle

Every month we try and update this database with for cle cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for cle cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.