超声引导高强度聚焦超声联合 PD-1 阻断治疗肺癌肝转移患者：一项单臂 2 期临床试验方案。

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.

机构信息

Respiratory Department, Xiangtan Central Hospital, Xiangtan, China.

Haifu Micro Noninvasive Center, Xiangtan Central Hospital, Xiangtan, China.

出版信息

JMIR Res Protoc. 2024 Nov 29;13:e59152. doi: 10.2196/59152.

DOI:10.2196/59152

PMID:39612480

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11645512/

Abstract

BACKGROUND

While 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.

OBJECTIVE

We 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.

METHODS

The 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.

RESULTS

The 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.

CONCLUSIONS

This 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 REGISTRATION

Chinese Clinical Trial Registry ChiCTR2200061076; https://www.chictr.org.cn/showproj.html?proj=170967.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/59152.

摘要

背景

免疫疗法已经彻底改变了肿瘤学的治疗方法，但它在肺癌伴肝转移患者中的疗效仍然有限，这可能是由于肝脏独特的免疫抑制微环境所致。局部肝脏治疗已被证明可以增强免疫治疗的反应，高强度聚焦超声（HIFU）作为一种微创的局部治疗方法，与免疫治疗联合使用已显示出有希望的结果。然而，关于肺癌伴肝转移患者中 HIFU 的临床数据有限。

目的

我们设计了 HILL（高强度聚焦超声联合免疫治疗肺癌肝转移患者）研究，旨在探讨 HIFU 联合免疫治疗肺癌伴肝转移的有效性和安全性。

方法

HILL 研究是一项单臂、单中心、二期临床试验，将纳入 30 例肺癌伴肝转移患者。治疗方案包括在首次接受程序性细胞死亡蛋白（PD）-1 阻断治疗前 1 周对肝转移灶进行 HIFU 治疗，然后每 3 周进行一次治疗。主要目的是根据免疫相关反应标准确定总体缓解率。次要目的包括安全性、无进展生存期、总体缓解率、总生存期和生活质量。还将在进展或复发时使用全血、血浆、存档的癌症组织和肿瘤活检进行探索性研究，以确定潜在的生物标志物。

结果

该研究于 2022 年 3 月 14 日获得资金，并于 2022 年 4 月 27 日获得伦理批准。临床试验注册于 2022 年 6 月 10 日完成，2022 年 7 月 10 日开始招募参与者。数据收集于 2022 年 7 月 14 日开始，首位患者入组。截至 2024 年 4 月，已招募 6 名参与者。预计结果将于 2026 年 12 月公布。