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

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the treatment Bronchoscopy + Cryobiopsy for Lung Cancer?

Research shows that using endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TBCB) can improve the accuracy of lung cancer diagnosis by providing larger tissue samples compared to traditional methods. This suggests that the treatment could be more effective in diagnosing lung cancer. ^{1 2 3 4 5}

Is bronchoscopy with cryobiopsy generally safe for humans?

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), a similar procedure, is generally considered safe with low complication rates, ranging from 0.22% to 1.44%, even in elderly patients. ^{5 6 7 8 9}

How is the treatment Bronchoscopy + Cryobiopsy for Lung Cancer different from other treatments?

This treatment is unique because it combines bronchoscopy with cryobiopsy, which allows for larger tissue samples compared to traditional methods like EBUS-TBNA (endobronchial ultrasound-guided transbronchial needle aspiration). This can lead to a more accurate diagnosis of lung cancer. ^{1 2 10 11 12}

Research Team

Fabien Maldonado, MD

Principal Investigator

Vanderbilt University/Ingram Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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 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]

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]

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]

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]

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]

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]

References

1. Spain pubmed.ncbi.nlm.nih.gov

Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy: series of 50 cases. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

The cryo-needle: a new tool for histological biopsies. A feasibility study. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Endobronchial ultrasound-guided transbronchial biopsy of peripheral pulmonary lesions: how many specimens are necessary? [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Endobronchial Ultrasound in Suspected Non-Malignant Mediastinal Lymphadenopathy. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

[A case of acute mediastinitis after endobronchial needle aspiration]. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Endobronchial ultrasound transbronchial needle aspiration in elderly patients: safety and performance outcomes EBUS-TBNA in elderly. [2022]

7. France pubmed.ncbi.nlm.nih.gov

[Mediastinal haematoma: A little known complication of ultrasound-guided trans-bronchial lymph node aspiration (EBUS-TBNA)]. [2019]

8. United States 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. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

EBUS-TBNA in elderly patients with lung cancer: safety and performance outcomes. [2016]

10. Brazil pubmed.ncbi.nlm.nih.gov

Diagnostic performance of cryobiopsy guided by radial-probe EBUS with a guide sheath for peripheral pulmonary lesions. [2023]

11. England 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. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Cryobiopsy increases the diagnostic yield of endobronchial biopsy: a multicentre trial. [2022]