EBUS-TBNA vs Transbronchial Mediastinal Cryobiopsy for Adequacy of Next Generation Sequencing (FROSTBITE-3)

January 29, 2026 updated by: Fabien Maldonado, Vanderbilt-Ingram Cancer Center

A Multicenter Randomized Trial of EBUS-TBNA Versus Transbronchial Mediastinal Cryobiopsy for Adequacy of Next Generation Sequencing

This is a multi-center clinical trial evaluating the effect of transbronchial mediastinal cryobiopsy 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 tissue acquisition for molecular analysis will be considered for enrollment and consented. Patients will only be enrolled if intraoperative ROSE suggests malignancy. Patients will be randomized to continue with the operator's initial EBUS-TBNA needle or switch to a cryoprobe to perform a sampling.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Primary Objective:

- To evaluate the utility of transbronchial mediastinal cryobiopsy 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:

  • The proportion of samples adequate for NGS testing
  • The 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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
250

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Vanderbilt-Ingram Services for Timely Access
  • Phone Number: 800-811-8480
  • Email: cip@vumc.org

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University/Ingram Cancer Center
        • Principal Investigator:
          • Fabien Maldonado, MD
        • Contact:
          • Vanderbilt-Ingram Service Services for Timely Access
          • Phone Number: 800-811-8480
          • Email: cip@vumc.org

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Lesions on PET or CT concerning for primary or metastatic malignancy that are amenable to biopsy by linear EBUS
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: EBUS-TBNA Group
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.
Procedure: Endobronchial ultrasound with transbronchial needle aspiration
Participants will undergo Endobronchial ultrasound with transbronchial needle aspiration
Procedure: Bronchoscopy
Participants will undergo Bronchoscopy
Experimental: Transbronchial Mediastinal Cryobiopsy Group
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.
Procedure: Endobronchial ultrasound with transbronchial needle aspiration
Participants will undergo Endobronchial ultrasound with transbronchial needle aspiration
Procedure: Bronchoscopy
Participants will undergo Bronchoscopy
Procedure: Cryobiopsy
Participants will undergo Cryobiopsy

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Proportion of samples sufficient for next-generation sequencing testing
Time Frame: Up to 12 months
Comparison of samples between arms that meet sufficiency criteria for NGS
Up to 12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Proportion of samples with adequate PD-1 / PD-L1 immunohistochemical staining
Time Frame: Up to 12 months
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
Time Frame: Up to 12 months
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
Time Frame: Up to 12 Months
Comparison of samples between arms of estimated tumor cells per H&E-stained field
Up to 12 Months
Histological disease subtyping
Time Frame: Up to 12 Months
Comparison of samples between arms for subtypes of lung malignancies (primary or metastatic)
Up to 12 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Vanderbilt-Ingram Cancer Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Medical University of South Carolina
Johns Hopkins University
Duke University
Virginia Commonwealth University
Northwestern Medicine

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Fabien Maldonado, MD, Vanderbilt University/Ingram Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 13, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 31, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 31, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 23, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 23, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 30, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 2, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 29, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • VICC-VDTHO23177
  • NCI-2023-08954 (Registry Identifier: NCI, Clinical Trials Reporting Program)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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