Clinical trial NCT04945317: ROSE for Improved Molecular Marker Testing Via EBUS
Official title: Rapid Onsite Cytopathologic Evaluation for Improved Molecular Marker Testing Via Endobronchial Ultrasound Bronchoscopy - A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Non-small Cell Lung Cancer (NSCLC)
Keywords: Endobronchial ultrasound (EBUS)
Rapid on-site evaluation (ROSE)
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2021-06-30
Enrollment: 349
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-center non-blinded randomized controlled trial (presence or absence of trained cytotechnologist providing on-site cytopathology feedback to bronchoscopist).
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of NGS biomarker testing attempts
timeFrame: within 60 days of procedure
Secondary outcomes:
measure: Level of Programmed Cell Death Protein 1 (PD-1)
timeFrame: within 60 days of procedure
measure: Number of targets
timeFrame: During Procedure
measure: Number of passes (ROSE arms only)
timeFrame: During Procedure
measure: Number of secondary procedures
timeFrame: During Procedure
measure: Need for repeat EBUS or another procedure
timeFrame: Within 30 days of procedure
measure: Procedure time
timeFrame: During Procedure
measure: Number of Procedural complications
timeFrame: Within 7 days of the procedure
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern Medicine
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Charleston
country: United States
facility: The Medical University of South Carolina (MUSC)
state: South Carolina
Study officials:
affiliation: Johns Hopkins University
name: Lonny Yarmus, DO, MBA
role: PRINCIPAL_INVESTIGATOR
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