Post-Market Study of Transbronchial Cryo-assisted RFA During Robotic Bronchoscopy With Subsequent Surgical Resection

Official title

Post-Market Study of Transbronchial Cryo-assisted RFA During Robotic Assisted Bronchoscopy With Subsequent Surgical Resection (CRONOS-CH)

Overview

The purpose of this study is to confirm the procedural feasibility and device usability of the HybridTherm® system during bronchoscopic cryo-assisted radiofrequency ablation (RFA) performed prior to scheduled surgical resection in patients with lung cancer. The bronchoscopy session includes tumor ablation and, when clinically indicated, mediastinal lymph node staging by EBUS-TBNA.

Detailed description

This is a prospective, single-arm, post-market clinical investigation conducted in Switzerland to collect clinical data on the use, safety, and performance of the CE-marked HybridTherm® system during routine bronchoscopic tumor management procedures. The investigation is classified as a ClinO-MD Category A1 medical device study, as the HybridTherm® system is CE-marked and used strictly within its intended purpose under normal conditions of clinical use.

The investigation is investigator-initiated and single-center, conducted at the University Hospital Zurich. The Sponsor-Investigator is responsible for the initiation, conduct, management, safety oversight, and data handling of the study in accordance with the Swiss Human Research Act (HRA), the Ordinance on Clinical Trials with Medical Devices (ClinO-MD), ISO 14155, and applicable ethical requirements. Ethics Committee approval is required prior to study initiation, and the investigation will begin only after a positive written decision from the competent cantonal ethics committee has been obtained.

The HybridTherm® system is a bipolar cryo-cooled radiofrequency ablation device intended for incision, coagulation, and ablation of tissue during flexible endoscopic procedures in the tracheobronchial system. The system provides internally cooled radiofrequency energy to delay tissue desiccation and impedance rise, thereby enabling controlled energy delivery during ablation. In this investigation, the device is used during clinically indicated bronchoscopic procedures without deviation from its approved indication or standard clinical workflow.

All enrolled participants undergo diagnostic bronchoscopy as part of routine clinical care, including mediastinal lymph node staging when clinically indicated. Transbronchial cryo-assisted radiofrequency ablation is performed during the same bronchoscopy session under general anesthesia. Surgical resection of the targeted lung lesion follows according to the established oncologic treatment plan and is not altered by study participation. No randomization, blinding, or comparator intervention is included.

Data collected in this investigation are derived exclusively from standard-of-care procedures, routine imaging, device readouts, and histopathological assessment of resected specimens. No additional diagnostic tests, therapeutic interventions, or protocol-mandated procedures beyond routine clinical practice are introduced. All analyses are descriptive in nature and are intended to support post-market evaluation of procedural feasibility, safety, and device usability.

The investigation is designed to generate clinical experience and safety data that may inform future clinical research and support the continued evaluation of bronchoscopic cryo-assisted radiofrequency ablation using the HybridTherm® system within standard treatment pathways.

Interventions

• Device HybridTherm® System
  Transbronchial cryo-assisted radiofrequency ablation (RFA) performed using the CE-marked HybridTherm® system during routine diagnostic bronchoscopy, within the intended use of the device.

Primary outcome measures

• Number of Participants with Successful Completion of Bronchoscopic Cryo-assisted RFA Using the HybridTherm® System [Time frame: Day 0 (Diagnostic Bronchoscopy and RFA Procedure)]
• Number of Participants with Bleeding-Related Serious Adverse Events Associated with the Investigational Device and/or RFA Procedure [Time frame: From Day 0 (Diagnostic Bronchoscopy and RFA Procedure) through End of Study (6-7 weeks post-procedure)]
• Severity of Bleeding-Related Adverse Events as Assessed by the Nashville Bleeding Scale [Time frame: From Day 0 (Diagnostic Bronchoscopy and RFA Procedure) through End of Study (6-7 weeks post-procedure)]

Secondary outcome measures (6)

• Total Number of Serious Adverse Events Related to the Investigational Device and/or RFA Procedure [Time frame: From Day 0 (Diagnostic Bronchoscopy and RFA Procedure) through End of Study (6-7 weeks post-procedure)]
• Total Number of Adverse Events Related to the Investigational Device and/or RFA Procedure [Time frame: From Day 0 (Diagnostic Bronchoscopy and RFA Procedure) through End of Study (6-7 weeks post-procedure)]
• Macroscopic and Microscopic Evidence of Ablation in the Resected Specimen [Time frame: At Surgical Resection (7-14 Days Post-Procedure)]
• Percentage of Tumor Necrosis Within the Ablation Zone [Time frame: At Surgical Resection (7-14 Days Post-Procedure)]
• Histopathologic Complete Response (Absence of Viable Tumor Cells) Within the Ablation Zone [Time frame: At Surgical Resection (7-14 Days Post-Procedure)]
• Composite Descriptive Intra-Procedural Metrics During Bronchoscopic Cryo-assisted RFA [Time frame: Day 0 (Diagnostic Bronchoscopy and RFA Procedure)]

Eligibility criteria

Inclusion criteria

• Patients who require diagnostic bronchoscopy for suspicious lung lesions with mediastinal lymph node status confirmed as NO by one of the following: Prior PET-CT showing no FDG-avid mediastinal lymph nodes, OR intraoperative EBUS-TBNA with ROSE confirming negative lymph nodes (performed when clinically indicated per section 6.1).
• Solitary pulmonary lesions ≤ 2.5cm with histologically or cytologically confirmed primary lung cancer.
• Suitable candidate for surgical resection of the tumor targeted for ablation
• Interdisciplinary tumor board consent
• Ability to read, understand, and sign patient Informed Consent Form (ICF)
• Age ≥ 18-years-old
• ≥ 20 mm of free space between the calculated intended ablation zone and the lung parenchyma or any critical structures (pleura, vessels and main bronchi).

Exclusion criteria

• Pregnant or nursing (breast feeding) females
• Central tumors abutting vital structures (main bronchus, pulmonary artery, esophagus, trachea)
• Thoracic electronic implants (e.g., pacemakers, ICDs)
• Uncorrectable coagulopathy or platelet count ≤ 50,000/mm³
• Patients receiving anticoagulant therapy or with pulmonary hypertension that, in the opinion of the Investigator, poses an unacceptable safety risk for bronchoscopy and ablation.
• Severe, uncontrolled comorbidities
• Active systemic infection
• Prior radiation therapy (SBRT) in the intended ablation zone
• Recent Investigational therapy within the last 30 days that the investigator deems could interfere with proceeding in the clinical investigation
• Tumors associated with atelectasis, obstructive pneumonitis, pleural effusion, or fibrosis
• Investigators determine that study participation poses safety risk
• Any comorbidities judged by the principal Investigator to be contraindicated for bronchoscopy
• Subject was judged unsuitable for study participation by the Investigator for any other reason

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Switzerland · 1 center

• University Hospital Zurich — Zurich

Publications

• Signoretti M, Valente R, Repici A, Delle Fave G, Capurso G, Carrara S. Endoscopy-guided ablation of pancreatic lesions: Technical possibilities and clinical outlook. World J Gastrointest Endosc. 2017 Feb 16;9(2):41-54. doi: 10.4253/wjge.v9.i2.41. PMID 28250896
• Dabizzi E, Testoni SG, Barbera M et al. 484 EUS-GUIDED CRYOTHERM ABLATION OF STAGE III PANCREATIC ADENOCARCINOMA: A PRELIMINARY RADIOLOGICAL PERSPECTIVE. Gastrointest Endosc 2018; 87: AB84
• Testoni SGG, Petrone MC, Reni M, Di Serio C, Rancoita PM, Rossi G, Balzano G, Linzenbold W, Enderle M, Della-Torre E, De Cobelli F, Falconi M, Capurso G, Arcidiacono PG. EUS-guided ablation with the HybridTherm Probe as second-line treatment in patients with locally advanced pancreatic ductal adenocarcinoma: A case-control study. Endosc Ultrasound. 2022 Sep-Oct;11(5):383-392. doi: 10.4103/EUS-D-21 PMID 36255026
• Testoni SGG, Petrone MC, Reni M, Rossi G, Barbera M, Nicoletti V, Gusmini S, Balzano G, Linzenbold W, Enderle M, Della-Torre E, De Cobelli F, Doglioni C, Falconi M, Capurso G, Arcidiacono PG. Efficacy of Endoscopic Ultrasound-Guided Ablation with the HybridTherm Probe in Locally Advanced or Borderline Resectable Pancreatic Cancer: A Phase II Randomized Controlled Trial. Cancers (Basel). 2021 Sep 8 PMID 34572743
• Arcidiacono PG, Carrara S, Reni M, Petrone MC, Cappio S, Balzano G, Boemo C, Cereda S, Nicoletti R, Enderle MD, Neugebauer A, von Renteln D, Eickhoff A, Testoni PA. Feasibility and safety of EUS-guided cryothermal ablation in patients with locally advanced pancreatic cancer. Gastrointest Endosc. 2012 Dec;76(6):1142-51. doi: 10.1016/j.gie.2012.08.006. Epub 2012 Sep 26. PMID 23021160
• Ahmed M, Liu Z, Afzal KS, Weeks D, Lobo SM, Kruskal JB, Lenkinski RE, Goldberg SN. Radiofrequency ablation: effect of surrounding tissue composition on coagulation necrosis in a canine tumor model. Radiology. 2004 Mar;230(3):761-7. doi: 10.1148/radiol.2303021801. PMID 14990840
• International Conference on Harmonization (ICH) Guideline for Good Clinical Practice E6(R2), (www.ich.org).
• Strahlenschutzverordnung (StSV) vom 26. April 2017 / Ordonnance sur la radioprotection (ORaP) du 26 avril 2017 / Ordinanza sulla radioprotezione (ORaP) del 26 aprile 2017

Identifiers

NCT: NCT07398027 · 639001022

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗