Hyperthermia Combined With Immune Checkpoint Inhibitor Therapy for Advanced Gastrointestinal Tumours
Condition: Gastrointestinal Tumor
MeSH terms: Digestive System Neoplasms; Gastrointestinal Neoplasms; Hyperthermia; Fever
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Water-filtered infrared A radiation whole-body hyperthermia (HECKEL 3000MT-4T, Germany); tislelizumab (BeiGene, China) combined with PD-1 inhibitor
Intervention type(s): Device; Drug
Intervention description(s): The patients were treated with whole-body hyperthermia (HECKEL 3000MT-4T, Germany)) on days 1 and 8 of each hyperthermia combined with immune checkpoint inhibitor treatment cycle along with administration of tislelizumab (BeiGene, China) 200 mg on day 2 (24 hours after the hyperthermia at day 1).; The patients were treated with whole-body hyperthermia (HECKEL 3000MT-4T, Germany)) on days 1 and 8 of each hyperthermia combined with immune checkpoint inhibitor treatment cycle along with administration of tislelizumab (BeiGene, China) 200 mg on day 2 (24 hours after the hyperthermia at day 1).
Other intervention name(s): Immune checkpoint inhibitor; PD-1 antibody
Intervention MeSH terms: Tislelizumab; Immune Checkpoint Inhibitors
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: hyperthermia; immune checkpoint inhibitor