TBNA vs EBUS-TBNA Plus Transbronchial Mediastinal Cryobiopsy for Adequacy of Next Generation Sequencing

Study Overview
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Brief Summary
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This is a multi-center, clinical trial evaluating the effect of adding transbronchial mediastinal cryobiopsy to EBUSTBNA for its ability to improve the likelihood of obtaining tissue sufficient for molecular analysis. Patients in outpatient clinics or pre-operative holding areas planning to undergo a bronchoscopic biopsy of a suspected malignant lesion (peripheral or mediastinal) for initial diagnosis, staging, or acquisition of tissue for molecular analysis will be considered for enrollment and consented. Patients will only be enrolled if intraoperative ROSE of a mediastinal 8 lymph node or mass suggests malignancy. Patients will be randomized to continue with the operator's initial EBUS-TBNA needle or switch to a cryoprobe to perform a transbronchial mediastinal cryobiopsy.

Detailed Description
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Primary Objective: - To evaluate the utility of adding transbronchial mediastinal cryobiopsy to endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) on its ability to improve the likelihood of acquiring tissue sufficient for next-generation sequencing (NGS). Safety Endpoints: Pneumothorax within 7 days of procedure Moderate bleeding defined as controlled with bronchoscope, saline, or epinephrine Serious bleeding is defined as uncontrolled, leading to respiratory failure, need for transfusion, or cardiovascular instability Respiratory failure is defined as a new oxygen requirement or escalation in oxygen delivery within 7 days of procedure Unplanned hospitalization related to the procedure within 7 days of procedure Death Exploratory Endpoints: Proportion of samples with adequate PD-1 / PD-L1 immunohistochemical staining Proportion of samples that are adequate for complete NGS library sequencing Estimated total number of tumor cells per H&E-stained slide Histological disease subtyping

Official Title
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A Multicenter Randomized Trial of EBUS-TBNA Versus EBUS-TBNA Plus Transbronchial Mediastinal Cryobiopsy for Adequacy of Next Generation Sequencing the META-Gen Study

Conditions
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Lung Cancer

Intervention / Treatment
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* Procedure: Endobronchial ultrasound with transbronchial needle aspiration
* Procedure: Bronchoscopy
* Procedure: Cryobiopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mediastinal lesion (lymph node or mass) on endobronchial ultrasound (EBUS) and/or PET/CT concerning for primary or metastatic malignancy Malignant cells present on rapid on-site cytological evaluation (ROSE) Exclusion Criteria: Patient is known to be less than 18 years old Patient is known to be pregnant Patient is known to be a prisoner Operator deems lesion is not safe to biopsy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: EBUS-TBNA Group<br>The same needle gauge will be used for these participant to acquire the initial diagnosis on ROSE (either 21 or 22G). Using standard sampling techniques, the mass or LN will be penetrated with the needle as confirmed by ultrasound, and the needle will be passed back from the proximal to the distal ends of the node to obtain the samples for an adequate cell block. The minimum number of cell passes to obtain a cell block will be set at three. | Procedure: Endobronchial ultrasound with transbronchial needle aspiration<br>* Participants will undergo Endobronchial ultrasound with transbronchial needle aspiration<br>Procedure: Bronchoscopy<br>* Participants will undergo Bronchoscopy<br>|
| Experimental: Transbronchial Mediastinal Cryobiopsy Group<br>The operator will switch to a flexible, single-use, 1.1 mm cryoprobe (Erbe 20402-401, Erbe, Tübingen, Germany) for these participants to obtain cryobiopsies. The operator will introduce the probe into the working channel of the EBUS bronchoscope. The cryoprobe will then be advanced toward the puncture site and inserted gently through the previous puncture site created by the initial EBUS-TBNA needle. The operator will confirm the placement of the probe via the EBUS image, and photo capture will be done. The cryo-probe will be activated and cooled for 3 seconds before retracting with the bronchoscope with the frozen biopsy tissue attached to the tip. The minimum number of freeze attempts to obtain a cell block will be set at three. | Procedure: Endobronchial ultrasound with transbronchial needle aspiration<br>* Participants will undergo Endobronchial ultrasound with transbronchial needle aspiration<br>Procedure: Bronchoscopy<br>* Participants will undergo Bronchoscopy<br>Procedure: Cryobiopsy<br>* Participants will undergo Cryobiopsy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of samples sufficient for next-generation sequencing testing | Comparison of samples between arms that meet sufficiency criteria for NGS | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of samples with adequate PD-1 / PD-L1 immunohistochemical staining | Comparison of samples between arms that meet PD-1/PD-L1 adequacy | Up to 12 months | 
| Proportion of samples that are adequate for complete NGS library sequencing | Comparison of samples between arms that meet sufficiency criteria and then are adequate for complete NGS library sequencing | Up to 12 months | 
| Estimated total number of tumor cells per H&E-stained slide | Comparison of samples between arms of estimated tumor cells per H&E-stained field | Up to 12 Months | 
| Histological disease subtyping | Comparison of samples between arms for subtypes of lung malignancies (primary or metastatic) | Up to 12 Months |