Ultrasound-Guided High-Intensity Focused Ultrasound Combined With PD-1 Blockade in Patients With Liver Metastases From Lung Cancer: Protocol for a Single-Arm Phase 2 Trial

BackgroundWhile immunotherapy has revolutionized oncological management, its efficacy in lung cancer patients with liver metastases remains limited, potentially due to the unique immunosuppressive microenvironment of the liver. Local liver treatment has been shown to enhance...

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Main Authors: Chao Hu, Qiang Fu, Fei Fei Gao, Jian Zeng, Wei Xiao, Hui Li, Li Peng, Xi Huang, Li Yang, Wen Zhi Chen, Ming Yan Jiang
Format: Article
Language:English
Published: JMIR Publications 2024-11-01
Series:JMIR Research Protocols
Online Access:https://www.researchprotocols.org/2024/1/e59152
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author Chao Hu
Qiang Fu
Fei Fei Gao
Jian Zeng
Wei Xiao
Hui Li
Li Peng
Xi Huang
Li Yang
Wen Zhi Chen
Ming Yan Jiang
author_facet Chao Hu
Qiang Fu
Fei Fei Gao
Jian Zeng
Wei Xiao
Hui Li
Li Peng
Xi Huang
Li Yang
Wen Zhi Chen
Ming Yan Jiang
author_sort Chao Hu
collection DOAJ
description BackgroundWhile immunotherapy has revolutionized oncological management, its efficacy in lung cancer patients with liver metastases remains limited, potentially due to the unique immunosuppressive microenvironment of the liver. Local liver treatment has been shown to enhance the immunotherapy response, and high-intensity focused ultrasound (HIFU), a minimally invasive local treatment, has demonstrated promising results in combination with immunotherapy. However, clinical data regarding HIFU in lung cancer with liver metastases are limited. ObjectiveWe designed the HILL (Ultrasound-Guided High-Intensity Focused Ultrasound Combined With PD-1 Blockade in Patients With Liver Metastases From Lung Cancer) study to investigate the effectiveness and safety of HIFU in combination with immunotherapy for lung cancer with liver metastases. MethodsThe HILL study is a single-armed, single-center, phase 2 clinical trial that will enroll 30 patients with lung cancer and liver metastases. The treatment regimen involves administering HIFU to liver metastases 1 week before the first dose of a programmed cell death protein (PD)–1 blockade, which is then administered every 3 weeks. The primary aim is to determine the overall response rate based on immune-related response criteria. Secondary aims include safety, progression-free survival, overall response, overall survival, and quality of life. Exploratory studies will also be conducted using whole blood, plasma, archival cancer tissue, and tumor biopsies during progression or relapse to identify potential biomarkers. ResultsThe study was funded on March 14, 2022, and received ethical approval on April 27, 2022. Clinical trial registration was completed by June 10, 2022, with participant recruitment beginning on July 10, 2022. Data collection commenced on July 14, 2022, with the enrollment of the first patient. By April 2024, 6 participants had been recruited. The results are expected to be published in December 2026. ConclusionsThis study seeks to improve treatment outcomes for lung cancer patients with liver metastases by combining HIFU and PD-1 inhibition. The study also aims to identify potential biomarkers through exploratory research that can aid in selecting patients for optimized outcomes in the future. Trial RegistrationChinese Clinical Trial Registry ChiCTR2200061076; https://www.chictr.org.cn/showproj.html?proj=170967 International Registered Report Identifier (IRRID)DERR1-10.2196/59152
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spelling doaj-art-6bbd41e9cbdd410aa9bb05eae166cafb2025-08-20T01:54:29ZengJMIR PublicationsJMIR Research Protocols1929-07482024-11-0113e5915210.2196/59152Ultrasound-Guided High-Intensity Focused Ultrasound Combined With PD-1 Blockade in Patients With Liver Metastases From Lung Cancer: Protocol for a Single-Arm Phase 2 TrialChao Huhttps://orcid.org/0000-0002-1229-9156Qiang Fuhttps://orcid.org/0009-0001-9463-1932Fei Fei Gaohttps://orcid.org/0009-0009-8260-0803Jian Zenghttps://orcid.org/0009-0007-0527-5627Wei Xiaohttps://orcid.org/0009-0003-4975-513XHui Lihttps://orcid.org/0000-0002-6561-7939Li Penghttps://orcid.org/0009-0007-5982-5532Xi Huanghttps://orcid.org/0009-0007-5116-0513Li Yanghttps://orcid.org/0009-0007-6523-873XWen Zhi Chenhttps://orcid.org/0000-0003-0097-3016Ming Yan Jianghttps://orcid.org/0000-0001-8558-2609 BackgroundWhile immunotherapy has revolutionized oncological management, its efficacy in lung cancer patients with liver metastases remains limited, potentially due to the unique immunosuppressive microenvironment of the liver. Local liver treatment has been shown to enhance the immunotherapy response, and high-intensity focused ultrasound (HIFU), a minimally invasive local treatment, has demonstrated promising results in combination with immunotherapy. However, clinical data regarding HIFU in lung cancer with liver metastases are limited. ObjectiveWe designed the HILL (Ultrasound-Guided High-Intensity Focused Ultrasound Combined With PD-1 Blockade in Patients With Liver Metastases From Lung Cancer) study to investigate the effectiveness and safety of HIFU in combination with immunotherapy for lung cancer with liver metastases. MethodsThe HILL study is a single-armed, single-center, phase 2 clinical trial that will enroll 30 patients with lung cancer and liver metastases. The treatment regimen involves administering HIFU to liver metastases 1 week before the first dose of a programmed cell death protein (PD)–1 blockade, which is then administered every 3 weeks. The primary aim is to determine the overall response rate based on immune-related response criteria. Secondary aims include safety, progression-free survival, overall response, overall survival, and quality of life. Exploratory studies will also be conducted using whole blood, plasma, archival cancer tissue, and tumor biopsies during progression or relapse to identify potential biomarkers. ResultsThe study was funded on March 14, 2022, and received ethical approval on April 27, 2022. Clinical trial registration was completed by June 10, 2022, with participant recruitment beginning on July 10, 2022. Data collection commenced on July 14, 2022, with the enrollment of the first patient. By April 2024, 6 participants had been recruited. The results are expected to be published in December 2026. ConclusionsThis study seeks to improve treatment outcomes for lung cancer patients with liver metastases by combining HIFU and PD-1 inhibition. The study also aims to identify potential biomarkers through exploratory research that can aid in selecting patients for optimized outcomes in the future. Trial RegistrationChinese Clinical Trial Registry ChiCTR2200061076; https://www.chictr.org.cn/showproj.html?proj=170967 International Registered Report Identifier (IRRID)DERR1-10.2196/59152https://www.researchprotocols.org/2024/1/e59152
spellingShingle Chao Hu
Qiang Fu
Fei Fei Gao
Jian Zeng
Wei Xiao
Hui Li
Li Peng
Xi Huang
Li Yang
Wen Zhi Chen
Ming Yan Jiang
Ultrasound-Guided High-Intensity Focused Ultrasound Combined With PD-1 Blockade in Patients With Liver Metastases From Lung Cancer: Protocol for a Single-Arm Phase 2 Trial
JMIR Research Protocols
title Ultrasound-Guided High-Intensity Focused Ultrasound Combined With PD-1 Blockade in Patients With Liver Metastases From Lung Cancer: Protocol for a Single-Arm Phase 2 Trial
title_full Ultrasound-Guided High-Intensity Focused Ultrasound Combined With PD-1 Blockade in Patients With Liver Metastases From Lung Cancer: Protocol for a Single-Arm Phase 2 Trial
title_fullStr Ultrasound-Guided High-Intensity Focused Ultrasound Combined With PD-1 Blockade in Patients With Liver Metastases From Lung Cancer: Protocol for a Single-Arm Phase 2 Trial
title_full_unstemmed Ultrasound-Guided High-Intensity Focused Ultrasound Combined With PD-1 Blockade in Patients With Liver Metastases From Lung Cancer: Protocol for a Single-Arm Phase 2 Trial
title_short Ultrasound-Guided High-Intensity Focused Ultrasound Combined With PD-1 Blockade in Patients With Liver Metastases From Lung Cancer: Protocol for a Single-Arm Phase 2 Trial
title_sort ultrasound guided high intensity focused ultrasound combined with pd 1 blockade in patients with liver metastases from lung cancer protocol for a single arm phase 2 trial
url https://www.researchprotocols.org/2024/1/e59152
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