ROSE for Improved Molecular Marker Testing Via EBUS

NCT ID: NCT04945317

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ENROLLING_BY_INVITATION

Clinical Phase

NA

Total Enrollment

349 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-14

Study Completion Date

2026-12-31

Brief Summary

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This research study is being done to compare two ways to conduct bronchoscopic biopsy of lymph nodes and other structures in the chest (i.e. the presence or absence of an on-site cytotechnologist performing a limited microscopic evaluation to provide non-binding feedback on specimen adequacy in real time during the procedure).

Detailed Description

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Endobronchial ultrasound (EBUS) is a highly safe and effective bronchoscopic procedure that can achieve diagnostic yields of over 90% for lung cancer - similar to those with the more-invasive surgical mediastinoscopy - with EBUS enjoying the advantage of a near 0% complication rate in several large studies. This has led to EBUS becoming the procedure of choice for mediastinal staging of lung cancer. Increasingly, bronchoscopists are being asked to perform EBUS not only for lung cancer staging but also for tissue acquisition for molecular markers to assess for mutations that can be treated with biologic therapy. However, a frequently encountered clinical scenario is that while an EBUS is diagnostic for lung cancer, it is non-diagnostic for molecular testing because of an insufficient amount of tissue material being collected. According to multiple studies, the "molecular yield" for EBUS in lung cancer can range from 74-82%. These studies have not specifically looked at adequacy of biomarkers, which could be distinctly different considering that evaluation of biomarkers requires more tissue for next generation sequencing (NGS). Currently, Johns Hopkins Hospital uses NGS as standard of care for identifying mutations associated with malignant cells. NGS analysis, which is usually reported as a percentage of cells that express one of many biomarkers currently being tested as standard of care, is performed via immunohistochemistry (IHC), necessitating the presence of a sufficiently cellular material with \>100 tumor cells for reliable quantitative characterization. To the investigator's knowledge, the rates of NGS biomarker sufficiency have not been prospectively analyzed to date.

Rapid on-site evaluation (ROSE) is an optional step during EBUS bronchoscopy in which an on-site cytotechnologist performs a limited microscopic evaluation to provide non-binding feedback on specimen adequacy in real time during the procedure. The cytotechnologist can also aid specimen processing e.g. through creation of a "tissue clot" in addition to use of the more standard liquid-based medium. At Johns Hopkins, EBUS procedures are routinely performed both with and without ROSE since the presence or absence of ROSE during EBUS has not been shown to impact diagnostic yield or procedural safety. However, its impact on NGS biomarker sufficiency has not been tested to the investigator's knowledge.

This study aims to investigate whether ROSE can impact NGS biomarker sufficiency by assisting the bronchoscopist in obtaining adequate tissue from the appropriate site. The hypothesis is that ROSE will decrease the rate of insufficient tumor tissue to permit NGS biomarker testing.

Conditions

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Non-small Cell Lung Cancer (NSCLC)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Multi-center non-blinded randomized controlled trial (presence or absence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist).
Primary Study Purpose

OTHER

Blinding Strategy

NONE

blinding not possible given nature of intervention

Study Groups

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ROSE clot arm

Presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist. Sample prepared as tissue clot.

Group Type OTHER

ROSE (presence of cytotech) & tissue clot sample

Intervention Type OTHER

Standard of care EBUS will include presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist during the procedure. Sample is a tissue clot.

NO-ROSE clot arm

Absence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist. Sample prepared as tissue clot.

Group Type OTHER

NO-ROSE (absence of cytotech) & tissue clot sample

Intervention Type OTHER

Standard of care EBUS will NOT include presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist during the procedure. Sample is a tissue clot.

ROSE liquid arm

Presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist. Sample prepared as liquid.

Group Type OTHER

ROSE (presence of cytotech) & liquid prep

Intervention Type OTHER

Standard of care EBUS will include presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist during the procedure. Sample is liquid.

NO-ROSE liquid arm

Absence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist. Sample prepared as

Group Type OTHER

NO-ROSE (absence of cytotech) & liquid prep

Intervention Type OTHER

Standard of care EBUS will NOT include presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist during the procedure. Sample is liquid.

Interventions

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ROSE (presence of cytotech) & liquid prep

Standard of care EBUS will include presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist during the procedure. Sample is liquid.

Intervention Type OTHER

NO-ROSE (absence of cytotech) & liquid prep

Standard of care EBUS will NOT include presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist during the procedure. Sample is liquid.

Intervention Type OTHER

ROSE (presence of cytotech) & tissue clot sample

Standard of care EBUS will include presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist during the procedure. Sample is a tissue clot.

Intervention Type OTHER

NO-ROSE (absence of cytotech) & tissue clot sample

Standard of care EBUS will NOT include presence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist during the procedure. Sample is a tissue clot.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Inpatients or outpatients \>18 years old
* Capable of informed consent
* Known or suspected non-small cell lung cancer (NSCLC)
* Referred to the interventional pulmonary team at Johns Hopkins Hospital (JHH), Johns Hopkins Bayview Medical Center (JHBMC), or other participating sites for tissue sampling of a hilar/mediastinal lymph node or another lesion accessible by convex-probe (CP) EBUS

Exclusion Criteria

* Refuse participation
* Standard contraindications to EBUS and bronchoscopy in general: bleeding disorders, antiplatelet or anticoagulant usage, high fraction of inspired oxygen (FiO2) requirement, and clinical instability
* Pregnant women
* Cytotechnologist not available at the time of screening, enrollment, or randomization
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lonny Yarmus, DO, MBA

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

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Northwestern Medicine

Chicago, Illinois, United States

Site Status

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, United States

Site Status

Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

The Medical University of South Carolina (MUSC)

Charleston, South Carolina, United States

Site Status

Countries

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United States

References

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Annema JT, van Meerbeeck JP, Rintoul RC, Dooms C, Deschepper E, Dekkers OM, De Leyn P, Braun J, Carroll NR, Praet M, de Ryck F, Vansteenkiste J, Vermassen F, Versteegh MI, Veselic M, Nicholson AG, Rabe KF, Tournoy KG. Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer: a randomized trial. JAMA. 2010 Nov 24;304(20):2245-52. doi: 10.1001/jama.2010.1705.

Reference Type BACKGROUND
PMID: 21098770 (View on PubMed)

Varela-Lema L, Fernandez-Villar A, Ruano-Ravina A. Effectiveness and safety of endobronchial ultrasound-transbronchial needle aspiration: a systematic review. Eur Respir J. 2009 May;33(5):1156-64. doi: 10.1183/09031936.00097908.

Reference Type BACKGROUND
PMID: 19407050 (View on PubMed)

Anantham D, Koh MS, Ernst A. Endobronchial ultrasound. Respir Med. 2009 Oct;103(10):1406-14. doi: 10.1016/j.rmed.2009.04.010. Epub 2009 May 15.

Reference Type BACKGROUND
PMID: 19447014 (View on PubMed)

Silvestri GA, Gonzalez AV, Jantz MA, Margolis ML, Gould MK, Tanoue LT, Harris LJ, Detterbeck FC. Methods for staging non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013 May;143(5 Suppl):e211S-e250S. doi: 10.1378/chest.12-2355.

Reference Type BACKGROUND
PMID: 23649440 (View on PubMed)

Sakakibara R, Inamura K, Tambo Y, Ninomiya H, Kitazono S, Yanagitani N, Horiike A, Ohyanagi F, Matsuura Y, Nakao M, Mun M, Okumura S, Inase N, Nishio M, Motoi N, Ishikawa Y. EBUS-TBNA as a Promising Method for the Evaluation of Tumor PD-L1 Expression in Lung Cancer. Clin Lung Cancer. 2017 Sep;18(5):527-534.e1. doi: 10.1016/j.cllc.2016.12.002. Epub 2016 Dec 22.

Reference Type BACKGROUND
PMID: 28111119 (View on PubMed)

Oezkan F, Khan A, Zarogoulidis P, Hohenforst-Schmidt W, Theegarten D, Yasufuku K, Nakajima T, Freitag L, Darwiche K. Efficient utilization of EBUS-TBNA samples for both diagnosis and molecular analyses. Onco Targets Ther. 2014 Nov 10;7:2061-5. doi: 10.2147/OTT.S72974. eCollection 2014.

Reference Type BACKGROUND
PMID: 25419143 (View on PubMed)

Jurado J, Saqi A, Maxfield R, Newmark A, Lavelle M, Bacchetta M, Gorenstein L, Dovidio F, Ginsburg ME, Sonett J, Bulman W. The efficacy of EBUS-guided transbronchial needle aspiration for molecular testing in lung adenocarcinoma. Ann Thorac Surg. 2013 Oct;96(4):1196-1202. doi: 10.1016/j.athoracsur.2013.05.066. Epub 2013 Aug 21.

Reference Type BACKGROUND
PMID: 23972930 (View on PubMed)

Yung RC, Otell S, Illei P, Clark DP, Feller-Kopman D, Yarmus L, Askin F, Gabrielson E, Li QK. Improvement of cellularity on cell block preparations using the so-called tissue coagulum clot method during endobronchial ultrasound-guided transbronchial fine-needle aspiration. Cancer Cytopathol. 2012 Jun 25;120(3):185-95. doi: 10.1002/cncy.20199. Epub 2011 Dec 5.

Reference Type BACKGROUND
PMID: 22144401 (View on PubMed)

Oki M, Saka H, Kitagawa C, Kogure Y, Murata N, Adachi T, Ando M. Rapid on-site cytologic evaluation during endobronchial ultrasound-guided transbronchial needle aspiration for diagnosing lung cancer: a randomized study. Respiration. 2013;85(6):486-92. doi: 10.1159/000346987. Epub 2013 Apr 3.

Reference Type BACKGROUND
PMID: 23571718 (View on PubMed)

Other Identifiers

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IRB00162151

Identifier Type: -

Identifier Source: org_study_id