Bronchoscopy + Cryobiopsy for Lung Cancer

(FROSTBITE-3 Trial)

Overseen By Vanderbilt-Ingram Services for Timely Access

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Vanderbilt-Ingram Cancer Center

Disqualifiers: Under 18, Pregnant, Prisoner, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 1 day

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two methods to improve lung cancer diagnosis by collecting tissue samples. One group uses a standard needle technique, while the other tries a newer method called cryobiopsy, which involves freezing and collecting tissue. The goal is to determine which method provides better tissue samples for analysis. Individuals with lung lesions suggesting cancer, who have been informed of a likely cancer diagnosis after a quick test in the clinic, might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking diagnostic advancement.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that transbronchial mediastinal cryobiopsy, a method for collecting lung tissue samples, is generally safe. Studies report few side effects or complications, indicating these issues are uncommon. The procedure uses a cryoprobe, which freezes a small piece of tissue for examination.

Studies comparing this method to traditional needle biopsies found similar safety levels. This suggests patients can feel confident about the associated risks.

Overall, evidence indicates that transbronchial mediastinal cryobiopsy is well-tolerated and safe for diagnosing lung cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores innovative biopsy techniques for lung cancer diagnosis. Unlike traditional methods that rely solely on needle aspiration, this trial investigates the use of cryobiopsy, which uses a special probe to freeze and extract tissue samples. This technique could offer more comprehensive tissue samples, potentially leading to more accurate diagnoses. By combining bronchoscopy with cryobiopsy, researchers hope to enhance the precision and effectiveness of lung cancer diagnostics, paving the way for better treatment decisions.

What evidence suggests that this trial's treatments could be effective for lung cancer?

This trial will compare the effectiveness of two diagnostic methods for lung conditions. Studies have shown that a transbronchial mediastinal cryobiopsy, which participants in one arm of this trial will receive, can be very effective for diagnosing lung conditions. Research indicates that cryobiopsies have a 91.2% success rate in identifying lung issues. In contrast, participants in another arm of this trial will undergo the traditional EBUS-TBNA method, which has a 56.2% success rate. This suggests that cryobiopsies are more likely to successfully identify and provide information about lung problems. Additionally, cryobiopsies are considered both safe and effective for diagnosing various conditions, including cancer and other lung diseases. These findings support the potential of cryobiopsy to improve lung cancer diagnosis. ^{1 2 6 7 8}

Who Is on the Research Team?

Fabien Maldonado, MD

Principal Investigator

Vanderbilt University/Ingram Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with suspected lung cancer who have a mediastinal lesion visible on ultrasound or PET/CT scans and malignant cells found in a quick onsite test. It's not for prisoners, those under 18, pregnant individuals, or if the doctor thinks it's unsafe to biopsy the lesion.

Inclusion Criteria

I have a suspicious mass in the chest area found by ultrasound or PET/CT.

Malignant cells were detected on ROSE.

Exclusion Criteria

I am under 18 years old.

Patient is known to be a prisoner

Patient is known to be pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants undergo either EBUS-TBNA or transbronchial mediastinal cryobiopsy for tissue sampling

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety endpoints such as pneumothorax, bleeding, and respiratory failure within 7 days of the procedure

1 week

Long-term Follow-up

Participants' samples are evaluated for adequacy in next-generation sequencing and other exploratory endpoints

Up to 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Bronchoscopy
• Cryobiopsy
• Endobronchial ultrasound with transbronchial needle aspiration

Trial Overview

The study compares two methods of obtaining lung tissue samples: standard needle aspiration (EBUS-TBNA) versus adding a freezing technique (cryobiopsy). The goal is to see if cryobiopsy improves getting enough tissue for advanced molecular testing.

How Is the Trial Designed?

Group I: Transbronchial Mediastinal Cryobiopsy Group Experimental Treatment 3 Interventions

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.

Group II: EBUS-TBNA Group Active Control 2 Interventions

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.

Bronchoscopy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Bronchoscopy for:

• Diagnostic purposes
• Therapeutic interventions
• Airway management

Approved in European Union as Bronchoscopy for:

• Diagnostic purposes
• Therapeutic interventions
• Airway management

Approved in Canada as Bronchoscopy for:

• Diagnostic purposes
• Therapeutic interventions
• Airway management

Who Is Running the Clinical Trial?

Vanderbilt-Ingram Cancer Center

Lead Sponsor

Trials

221

Recruited

64,400+

Northwestern Medicine

Collaborator

Trials

14

Recruited

9,500+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

The study demonstrated that the cryo-needle can successfully obtain larger and high-quality histological specimens from lymph nodes compared to traditional methods, with significant increases in size and weight of biopsies at longer activation times.

Both cryo-needle and EBUS-TBNA techniques showed similar safety profiles, as there was no difference in bleeding duration between the two methods, indicating that cryo-needle biopsies are a safe alternative for lymph node sampling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cryo-needle: a new tool for histological biopsies. A feasibility study. Franke, KJ., Nilius, G., Ruehle, KH., et al.[2021]

In a study of 50 patients with mediastinal lymphadenopathy, transbronchial mediastinal cryobiopsy (EBUS-TBCB) significantly improved diagnostic accuracy from 64% to 90% compared to endobronchial ultrasonography-guided transbronchial fine-needle aspiration (EBUS-TBNA).

EBUS-TBCB was found to be more sensitive in detecting both malignant and inflammatory diseases, with only 6 mild complications that resolved during the procedure, indicating it is a safe and effective alternative to EBUS-TBNA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy: series of 50 cases. Salcedo Lobera, E., Codeso, FMP., Casado Miranda, E.[2023]

A case report highlights a rare complication of endobronchial ultrasound-guided trans-bronchial needle aspiration (EBUS-TBNA), where a 65-year-old man developed a subcarinal hematoma and hemoptysis after the procedure, likely due to puncture of a bronchial artery.

The complication occurred during a transition between anticoagulant treatments, suggesting that special caution is needed when performing EBUS-TBNA in patients undergoing changes in anticoagulation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Mediastinal haematoma: A little known complication of ultrasound-guided trans-bronchial lymph node aspiration (EBUS-TBNA)]. Fedi, A., Thony, F., Ferretti, GR., et al.[2019]

In a study of 15 lesions, EBUS-TBNA was successfully performed in 11 cases, demonstrating that the procedure is feasible in bronchi with a mean internal diameter of at least 4.5 mm.

No complications were reported during the procedure, indicating that EBUS-TBNA is a safe method for diagnosing lesions adjacent to narrow bronchi.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The usefulness of endobronchial ultrasonography-guided transbronchial needle aspiration at the lobar, segmental, or subsegmental bronchus smaller than a convex-type bronchoscope. Kurimoto, N., Inoue, T., Miyazawa, T., et al.[2022]

In a study involving 600 patients suspected of having endobronchial tumors, cryobiopsy achieved a definitive diagnosis in 95.0% of cases, compared to 85.1% for conventional forceps biopsy, indicating a significantly higher diagnostic yield (p<0.001).

Cryobiopsy was found to be a safe procedure, with no increase in the incidence of significant bleeding compared to traditional biopsy methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cryobiopsy increases the diagnostic yield of endobronchial biopsy: a multicentre trial. Hetzel, J., Eberhardt, R., Herth, FJ., et al.[2022]

Transbronchial lung cryobiopsy (TBCB) guided by radial-probe EBUS (RP-EBUS) without fluoroscopy showed a high diagnostic yield of 77.4%, significantly better than the 59.4% yield from traditional transbronchial forceps biopsy (TBFB) in a study of 133 patients.

Lesion size and location were important factors influencing the success of TBCB, with larger lesions and those not located in the upper lobes yielding better diagnostic results, indicating that TBCB is particularly effective for certain types of peripheral pulmonary lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic performance of cryobiopsy guided by radial-probe EBUS with a guide sheath for peripheral pulmonary lesions. Chen, H., Yu, X., Yu, Y., et al.[2023]

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a safe and well-tolerated procedure for elderly patients (≥70 years), showing similar complication rates compared to younger patients, despite requiring lower sedation levels.

In elderly patients with lung cancer, EBUS-TBNA demonstrated higher diagnostic accuracy (96.0%) and negative predictive value (91.8%) for nodal sampling, indicating its efficacy in accurately staging and diagnosing lung cancer in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EBUS-TBNA in elderly patients with lung cancer: safety and performance outcomes. Evison, M., Crosbie, PA., Martin, J., et al.[2016]

Cryobiopsy of mediastinal lymph nodes (cryoEBUS) demonstrated a higher diagnostic yield compared to conventional EBUS-TBNA, with an overall effectiveness of 92% versus 80%, particularly excelling in diagnosing lymphomas and benign conditions.

The procedure allows for better characterization of lymphoma subtypes and enables genetic studies in 97% of samples, while maintaining a safety profile with no serious complications reported, although light bleeding occurred in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is the diagnostic yield of mediastinal lymph node cryobiopsy (cryoEBUS) better for diagnosing mediastinal node involvement compared to endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)? A systematic review. Botana-Rial, M., Lojo-Rodríguez, I., Leiro-Fernández, V., et al.[2023]

A 67-year-old man developed acute mediastinitis 13 days after undergoing EBUS-TBNA to diagnose an enlarged mediastinal lymph node, highlighting a rare but serious complication of the procedure.

Prompt treatment with antibiotics led to significant improvement in his symptoms and laboratory markers, emphasizing the importance of monitoring for complications after EBUS-TBNA, especially in cases involving necrotic lymph nodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A case of acute mediastinitis after endobronchial needle aspiration]. Kurimoto, N., Shinmyo, T., Tagay, R., et al.[2013]

In a study of 315 patients undergoing EBUS-TBNA for suspected non-malignant lymphadenopathy, the procedure identified specific causes in about one-third of cases, with a high specificity of 96%.

The most common findings included non-specific inflammation and epithelioid cell granulomas, while microbiological testing successfully identified infections in 3 patients, demonstrating the efficacy of EBUS-TBNA in diagnosing non-malignant conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endobronchial Ultrasound in Suspected Non-Malignant Mediastinal Lymphadenopathy. Eickhoff, L., Golpon, H., Zardo, P., et al.[2022]

In a study of 132 patients who underwent EBUS-TBNA, 29.5% were aged 70 and older, and despite having more comorbidities and worse overall health, these older patients experienced no increase in complications compared to younger patients.

The diagnostic performance of EBUS-TBNA was consistent across age groups, indicating that this procedure is safe and effective for elderly patients, regardless of their health status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endobronchial ultrasound transbronchial needle aspiration in elderly patients: safety and performance outcomes EBUS-TBNA in elderly. Olgun Yıldızeli, Ş., Tufan, A., Bozkurtlar, E., et al.[2022]

In a study of 384 patients undergoing EBUS-guided transbronchial biopsy for peripheral pulmonary lesions, the overall diagnostic yield was 73%, with probe position being the key factor influencing this yield.

When the EBUS probe was placed directly within the lesions, the diagnostic yield increased to 85%, while positioning adjacent to or outside the lesions resulted in a much lower yield of 38%, indicating that the optimal number of biopsy specimens should be tailored to individual cases rather than a fixed number.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endobronchial ultrasound-guided transbronchial biopsy of peripheral pulmonary lesions: how many specimens are necessary? Huang, CT., Tsai, YJ., Liao, WY., et al.[2022]

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