Accepted for/Published in: JMIR Research Protocols
Date Submitted: Apr 3, 2024
Date Accepted: Oct 26, 2024
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 II Trial
ABSTRACT
Background:
Immunotherapy have greatly improved oncological management but their benefit for lung cancer patients with liver metastases is limited. This could be due to the unique immunosuppressive microenvironment of the liver. The addition of local liver treatment has been shown to enhance immunotherapy efficacy. High-intensity focused ultrasound (HIFU), a repeatable and minimally invasive local treatment, has shown encouraging efficacy in combination with immunotherapy, while clinical data in lung cancer with liver metastases are limited.
Objective:
Therefore, we designed the HILL study to investigate the effectiveness and safety of HIFU in combination with immunotherapy for lung cancer with liver metastases.
Methods:
HILL study is a single-armed, single-centre, phase II study in lung cancer patients with liver metastases. Treatment consists of HIFU in liver metastases within 1weeks before the first PD-1blockade dose. PD-1 blockade is administered 3-weekly, and total cycles are evaluated by Investigators relying on clinical guidelines. HIFU is given on week 1 of the first PD-1blockade dose. In total,30 evaluable patients for lung cancer with liver metastases are foreseen to enrol. The primary objective is to determine, at week 18, the objective response rate based on immune-related response criteria. Safety, progression-free survival, the best overall response, overall survival, and quality of life are secondary aims. In addition, whole blood, plasma, archival cancer tissue, and tumour biopsies during progression/relapse are obtained for exploratory studies.
Results:
The HILL study was funded by the State Key Laboratory of Ultrasound Medical Engineering of Chongqing Medical University in January 2022, and the first patient was enrolled in July 2022. By May 2024, we had enrolled a total of 6 patients, and no data analysis was carried out for the time being.
Conclusions:
This study aims to overcome the limited benefit and immunosuppressive tumor microenvironment in lung cancer patients with liver metastases by combining HIFU and PD-1 inhibition. Exploratory research is conducted to identify potential biomarkers that may help to choose accurate patients to optimize future outcomes. Clinical Trial: ClinicalTrials.gov Identifier: ChiCTR2200061076. Registered on June 10, 2022.
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