Hyperthermia Combined With Immune Checkpoint Inhibitors in the Treatment of Advanced Gastrointestinal Malignancies With Liver Metastases: A Multicenter, Open-label, Dual-cohort Phase II Exploratory Clinical Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 40
- 主要终点
- Objective Response Rate
研究概览
简要总结
This study aims to explore the synergistic antitumor effects and safety of hyperthermia combined with immune checkpoint inhibitors (ICIs) in patients with advanced gastrointestinal malignancies with liver metastases. Liver metastasis represents a common cause of treatment failure in gastrointestinal cancers, and the response rate to ICIs remains suboptimal in certain patients with liver metastases, potentially attributable to the immunosuppressive hepatic microenvironment. The combination of hyperthermia with ICIs, chemotherapy, or other therapeutic modalities may further enhance treatment efficacy. Hyperthermia could potentially reverse immunosuppression and improve ICI effectiveness through mechanisms including enhanced tumor blood perfusion, promoted antigen presentation, and increased immune cell infiltration. This multicenter, open-label, dual-cohort phase II trial will evaluate patients stratified by tumor type (colorectal cancer versus gastric cancer) to assess the objective response rate (ORR), progression-free survival (PFS), and safety profile of hyperthermia-ICI combination therapy. Concurrently, dynamic monitoring of peripheral immune markers (such as neutrophil-to-lymphocyte ratio and interleukins) and tumor microenvironment alterations will be conducted to identify potential predictive biomarkers, thereby providing preliminary evidence for subsequent phase III investigations. The ultimate objective is to develop more effective combination treatment strategies for patients with advanced gastrointestinal malignancies accompanied by liver metastases.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18 and 75 years, male or female.
- •Histologically or cytologically confirmed diagnosis of gastrointestinal malignancy with liver metastases.
- •Prior treatment requirements:
- •Gastric cancer patients must have received at least one prior line of systemic therapy.
- •Colorectal cancer patients must have received at least two prior lines of systemic therapy.
- •Clinically assessed as suitable for hyperthermia combined with immune checkpoint inhibitor therapy.
- •At least one measurable lesion meeting RECIST 1.1 criteria.
- •Expected survival ≥6 months.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Adequate organ and bone marrow function.
- •Willingness to provide sufficient baseline and post-treatment samples, ability to comply with long-term follow-up and evaluation, and signed informed consent.
- •No prior history of other malignancies.
排除标准
- •Pregnant or lactating women.
- •Any comorbidities or underlying medical conditions that, in the investigator's judgment, render the patient unsuitable for study participation.
- •Presence of other severe physical or psychiatric disorders, or clinically significant laboratory abnormalities that may increase the risk associated with study participation, interfere with study results interpretation, or otherwise make the patient inappropriate for inclusion as determined by the investigator.
研究组 & 干预措施
Cohort 1: gastric cancer
Gastric cancer patients must have received at least one prior line of systemic therapy.
干预措施: Hyperthermia (Procedure)
Cohort 1: gastric cancer
Gastric cancer patients must have received at least one prior line of systemic therapy.
干预措施: Immunotherapy (Drug)
Cohort 2: colorectal cancer
Colorectal cancer patients must have received at least two prior lines of systemic therapy.
干预措施: Hyperthermia (Procedure)
Cohort 2: colorectal cancer
Colorectal cancer patients must have received at least two prior lines of systemic therapy.
干预措施: Immunotherapy (Drug)
结局指标
主要结局
Objective Response Rate
时间窗: From the start of treatment to tumor progression or death from any cause (whichever occurs first, at least 4 weeks, assessed up to 12 months).
Objective response rate (ORR) refers to the proportion of patients whose tumor volume has shrunk to the pre-specified value and can maintain the minimum duration requirement (at least 4 weeks, assessed up to 12 months) by the RECIST (Version 1.1), which is the sum of the proportions of complete response (CR) and partial response (PR).
次要结局
- Progression Free Survival(Progression-free survival (PFS) refers to the time from the start of treatment to tumor progression or death from any cause (whichever occurs first, at least 4 weeks, assessed up to 12 months).)
- Disease Control Rate(From the start of treatment to tumor progression or death from any cause (whichever occurs first, at least 4 weeks, assessed up to 12 months).)
- Overall Survival(From study enrollment through 12 months post-treatment completion of the last participant.)
研究者
Xiujuan Qu
Director
China Medical University, China