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

Vanderbilt University Medical Center

Status and phase: Enrolling; Phase 4

Conditions: Lung Cancer

Treatments: Procedure: Cryobiopsy; Procedure: Bronchoscopy; Procedure: Endobronchial ultrasound with transbronchial needle aspiration

Study type: Interventional

Funder types: Other

Identifiers

NCT06105801

VICC-VDTHO23177

NCI-2023-08954 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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

Enrollment: 250 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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250 participants in 2 patient groups

EBUS-TBNA Group

Active Comparator group

Description:

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.

Treatment:

Procedure: Endobronchial ultrasound with transbronchial needle aspiration

Procedure: Bronchoscopy

Transbronchial Mediastinal Cryobiopsy Group

Experimental group

Description:

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.

Treatment:

Procedure: Endobronchial ultrasound with transbronchial needle aspiration

Procedure: Bronchoscopy

Procedure: Cryobiopsy