Lung CancerPhase 4FROSTBITE-3NCT06105801
EBUS-TBNA vs Transbronchial Mediastinal Cryobiopsy for Adequacy of Next Generation Sequencing
A Phase 4 study testing Endobronchial ultrasound with transbronchial needle aspiration, Bronchoscopy and Cryobiopsy in people with Lung Cancer, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer
- What is being tested?
- Endobronchial ultrasound with transbronchial needle aspiration, Bronchoscopy and Cryobiopsy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Sep 2024to 31 Oct 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Vanderbilt-Ingram Service Services for Timely Access, 800-811-8480, cip@vumc.org
Fabien Maldonado, MD
About this study
Official title: 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.
Read the 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
- Conditions
- Lung Cancer
- Being tested
- Endobronchial ultrasound with transbronchial needle aspiration, Bronchoscopy, Cryobiopsy
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Endobronchial ultrasound with transbronchial needle aspirationProcedure or surgery
Participants will undergo Endobronchial ultrasound with transbronchial needle aspiration
BronchoscopyProcedure or surgery
Participants will undergo Bronchoscopy
CryobiopsyProcedure or surgery
Participants will undergo Cryobiopsy
| Study group | Role | What they receive |
|---|---|---|
| EBUS-TBNA Group | Active comparator | 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. Receives: Procedure: Endobronchial ultrasound with transbronchial needle aspiration; Procedure: Bronchoscopy |
| Transbronchial Mediastinal Cryobiopsy Group | Experimental | 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. Receives: Procedure: Endobronchial ultrasound with transbronchial needle aspiration; Procedure: Bronchoscopy; Procedure: Cryobiopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of samples sufficient for next-generation sequencing testing
Comparison of samples between arms that meet sufficiency criteria for NGS
Measured: Up to 12 months
Secondary outcomes (4)
Proportion of samples with adequate PD-1 / PD-L1 immunohistochemical staining
Comparison of samples between arms that meet PD-1/PD-L1 adequacy
Measured: 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
Measured: 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
Measured: Up to 12 Months
Histological disease subtyping
Comparison of samples between arms for subtypes of lung malignancies (primary or metastatic)
Measured: Up to 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2023
- Study start13 Sep 2024
- Primary completion31 Oct 2027 (estimated)
- Study completion31 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Northwestern Medicine, Johns Hopkins University, Duke University, Medical University of South Carolina, Virginia Commonwealth University
- Responsible party
- Principal investigator, Fabien Maldonado, Vanderbilt-Ingram Cancer Center
- Investigators
- Fabien Maldonado, MD, Principal investigator, Vanderbilt University/Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06105801
- Sponsor's protocol ID
- VICC-VDTHO23177
- Other IDs
- NCI-2023-08954
- Acronym
- FROSTBITE-3
- Status last verified
- Jan 2026
- First submitted
- 23 Oct 2023
- Last updated
- 2 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Randomized Trial of EBUS-TBNA Versus Transbronchial Mediastinal Cryobiopsy for Adequacy of Next Generation Sequencing
- ClinicalTrials.gov ID
- NCT06105801
- Acronym / sponsor ID
- FROSTBITE-3 / VICC-VDTHO23177
- Conditions
- Lung Cancer
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- Northwestern Medicine, Johns Hopkins University, Duke University, Medical University of South Carolina, Virginia Commonwealth University
- Study start
- 13 Sep 2024 (actual)
- Primary completion
- 31 Oct 2027 (estimated)
- Study completion
- 31 Oct 2028 (estimated)
- First posted
- 30 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EBUS-TBNA Group | Active comparator | Procedure: Endobronchial ultrasound with transbronchial needle aspiration, Procedure: BronchoscopyThe 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. |
| Transbronchial Mediastinal Cryobiopsy Group | Experimental | Procedure: Endobronchial ultrasound with transbronchial needle aspiration, Procedure: Bronchoscopy, Procedure: CryobiopsyThe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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)
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Endobronchial ultrasound with transbronchial needle aspirationParticipants will undergo Endobronchial ultrasound with transbronchial needle aspiration | Procedure or surgery | EBUS-TBNA Group, Transbronchial Mediastinal Cryobiopsy Group |
| BronchoscopyParticipants will undergo Bronchoscopy | Procedure or surgery | EBUS-TBNA Group, Transbronchial Mediastinal Cryobiopsy Group |
| CryobiopsyParticipants will undergo Cryobiopsy | Procedure or surgery | Transbronchial Mediastinal Cryobiopsy Group |
Primary outcome
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
4 secondary outcomes
Proportion of samples with adequate PD-1 / PD-L1 immunohistochemical staining
Time frame: Up to 12 months
Proportion of samples that are adequate for complete NGS library sequencing
Time frame: Up to 12 months
Estimated total number of tumor cells per H&E-stained slide
Time frame: Up to 12 Months
Histological disease subtyping
Time frame: Up to 12 Months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Fabien Maldonado, MD principal investigator
Vanderbilt University/Ingram Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Endobronchial ultrasound with transbronchial needle aspiration, Bronchoscopy and Cryobiopsy in people with Lung Cancer, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vanderbilt-Ingram Services for Timely Access (800-811-8480, cip@vumc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of samples sufficient for next-generation sequencing testing (time frame: Up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2026.