Water-filtered Infrared A Radiation Whole-body Hyperthermia Combined With Immune Checkpoint Inhibitor Therapy for Advanced Gastrointestinal Tumours: A Prospective Open-label Single-arm Phase 2 Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- disease control rate (DCR)
研究概览
简要总结
Gastrointestinal tumours (GITs) are the most common and fatal cancers worldwide; 96% of GITs show the microsatellite-stable (MSS)/proficient mismatch repair (pMMR) phenotype, and these tumours have a poor response to immune checkpoint inhibitor (ICI) therapy. Hyperthermia combined with ICI treatment (HIT) has been reported to show a synergistic sensitisation effect in numerous basic studies. This study aimed to validate the effectiveness, safety, and feasibility of water-filtered infrared A radiation (WIRA) whole-body hyperthermia combined with PD-1 inhibitor therapy and evaluate the real-world clinical application prospects of HIT. This open-label single-arm phase 2 clinical trial aimed to enrol advanced GIT patients with the MSS/pMMR phenotype in the East Asian population who had received third-line or higher treatment. The patients were treated with whole-body hyperthermia on days 1 and 8 of each HIT cycle along with administration of tislelizumab 200 mg on day 2 (24 h after the hyperthermia at day 1). The primary outcome was the disease control rate (DCR), while the secondary outcomes were progression-free survival (PFS), overall survival (OS), safety, and improvement in quality of life.
详细描述
The specific treatment process is shown in the trial flow diagram. The patients underwent WIRA whole-body hyperthermia on days 1 and 8 of each HIT cycle. On day 2 (24 h after hyperthermia on day 1), 200 mg of tislelizumab prepared with 100 mL of normal saline was intravenously administered for less than 30 min. After six HIT cycles, tislelizumab was administered intravenously every 21 days until drop-out. For quality control of hyperthermia, the core temperature was set to 38·5-39·5 °C and measured using a rectal temperature-sensing probe. Hyperthermia was considered to have been achieved when this temperature range was recached and maintained for 60 min. Each hyperthermia session lasted for 2 h, including a 30-min heating stage, a 60-min insulation stage, and a 30-min cooling stage. Clinical data were collected every two HIT treatment cycles and evaluated using the RECIST version 1.1 standard.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Patients with advanced GIT who have previously received third-line or above treatment.
- •Patients are aged 18-
- •Patients with at least one measurable tumor lesion.
- •Patients' all physiological indexes meet the HIT requirements.
排除标准
- •Patients have participated in other clinical trials within 4 weeks before enrollment.
- •Patients contraindicate to whole-body hyperthermia.
- •Patients contraindicate to immunotherapy.
- •Patients cannot fully cooperate with HIT and follow-up.
- •Pregnant or lactating women.
- •Other circumstances may affect the results.
研究组 & 干预措施
hyperthermia combined with immune checkpoint inhibitor group
The patients were treated with whole-body hyperthermia on days 1 and 8 of each HIT cycle along with administration of tislelizumab 200 mg on day 2 (24 h after the hyperthermia at day 1).
干预措施: Water-filtered infrared A radiation whole-body hyperthermia (HECKEL 3000MT-4T, Germany) (Device)
hyperthermia combined with immune checkpoint inhibitor group
The patients were treated with whole-body hyperthermia on days 1 and 8 of each HIT cycle along with administration of tislelizumab 200 mg on day 2 (24 h after the hyperthermia at day 1).
干预措施: tislelizumab (BeiGene, China) combined with PD-1 inhibitor (Drug)
结局指标
主要结局
disease control rate (DCR)
时间窗: up to 6 months
DCR=(PR+CR) / (PD+SD+PR+CR) \* 100%
次要结局
- progression-free survival (PFS)(up to 36 months)
- overall survival (OS)(up to 36 months)
研究者
Pengyuan Liu
Research Secretary
Zhejiang Hospital