xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06022692</url>
    </required_header>
    <id_info>
      <org_study_id>ZhejiangH</org_study_id>
      <nct_id>NCT06022692</nct_id>
    </id_info>
    <brief_title>Hyperthermia Combined With Immune Checkpoint Inhibitor Therapy for Advanced Gastrointestinal Tumours</brief_title>
    <acronym>HEAIS001</acronym>
    <official_title>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</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Pengyuan Liu</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Zhejiang Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Zhejiang Hospital</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Gastrointestinal tumours (GITs) are the most common and fatal cancers worldwide; 96% of GITs&#xD;
        show the microsatellite-stable (MSS)/proficient mismatch repair (pMMR) phenotype, and these&#xD;
        tumours have a poor response to immune checkpoint inhibitor (ICI) therapy. Hyperthermia&#xD;
        combined with ICI treatment (HIT) has been reported to show a synergistic sensitisation&#xD;
        effect in numerous basic studies. This study aimed to validate the effectiveness, safety, and&#xD;
        feasibility of water-filtered infrared A radiation (WIRA) whole-body hyperthermia combined&#xD;
        with PD-1 inhibitor therapy and evaluate the real-world clinical application prospects of&#xD;
        HIT. This open-label single-arm phase 2 clinical trial aimed to enrol advanced GIT patients&#xD;
        with the MSS/pMMR phenotype in the East Asian population who had received third-line or&#xD;
        higher treatment. The patients were treated with whole-body hyperthermia on days 1 and 8 of&#xD;
        each HIT cycle along with administration of tislelizumab 200 mg on day 2 (24 h after the&#xD;
        hyperthermia at day 1). The primary outcome was the disease control rate (DCR), while the&#xD;
        secondary outcomes were progression-free survival (PFS), overall survival (OS), safety, and&#xD;
        improvement in quality of life.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The specific treatment process is shown in the trial flow diagram. The patients underwent&#xD;
        WIRA whole-body hyperthermia on days 1 and 8 of each HIT cycle. On day 2 (24 h after&#xD;
        hyperthermia on day 1), 200 mg of tislelizumab prepared with 100 mL of normal saline was&#xD;
        intravenously administered for less than 30 min. After six HIT cycles, tislelizumab was&#xD;
        administered intravenously every 21 days until drop-out. For quality control of hyperthermia,&#xD;
        the core temperature was set to 38·5-39·5 °C and measured using a rectal temperature-sensing&#xD;
        probe. Hyperthermia was considered to have been achieved when this temperature range was&#xD;
        recached and maintained for 60 min. Each hyperthermia session lasted for 2 h, including a&#xD;
        30-min heating stage, a 60-min insulation stage, and a 30-min cooling stage. Clinical data&#xD;
        were collected every two HIT treatment cycles and evaluated using the RECIST version 1.1&#xD;
        standard.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">June 1, 2020</start_date>
    <completion_date type="Actual">August 1, 2023</completion_date>
    <primary_completion_date type="Actual">May 31, 2022</primary_completion_date>
    <phase>Phase 1/Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>disease control rate (DCR)</measure>
      <time_frame>up to 6 months</time_frame>
      <description>DCR=(PR+CR) / (PD+SD+PR+CR) * 100%</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>progression-free survival (PFS)</measure>
      <time_frame>up to 36 months</time_frame>
      <description>The time between enrollment and tumor progression (in any aspect) or death (for any reason).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>overall survival (OS)</measure>
      <time_frame>up to 36 months</time_frame>
      <description>The time between enrollment and death (for any reason).</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Actual">18</enrollment>
    <condition>Gastrointestinal Tumor</condition>
    <arm_group>
      <arm_group_label>hyperthermia combined with immune checkpoint inhibitor group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>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).</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Water-filtered infrared A radiation whole-body hyperthermia (HECKEL 3000MT-4T, Germany)</intervention_name>
      <description>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).</description>
      <arm_group_label>hyperthermia combined with immune checkpoint inhibitor group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>tislelizumab (BeiGene, China) combined with PD-1 inhibitor</intervention_name>
      <description>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).</description>
      <arm_group_label>hyperthermia combined with immune checkpoint inhibitor group</arm_group_label>
      <other_name>Immune checkpoint inhibitor</other_name>
      <other_name>PD-1 antibody</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients with advanced GIT who have previously received third-line or above treatment.&#xD;
  &#xD;
            -  Patients are aged 18-75.&#xD;
  &#xD;
            -  Patients with at least one measurable tumor lesion.&#xD;
  &#xD;
            -  Patients' all physiological indexes meet the HIT requirements.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients have participated in other clinical trials within 4 weeks before enrollment.&#xD;
  &#xD;
            -  Patients contraindicate to whole-body hyperthermia.&#xD;
  &#xD;
            -  Patients contraindicate to immunotherapy.&#xD;
  &#xD;
            -  Patients cannot fully cooperate with HIT and follow-up.&#xD;
  &#xD;
            -  Pregnant or lactating women.&#xD;
  &#xD;
            -  Other circumstances may affect the results.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jun Chen</last_name>
      <role>Study Director</role>
      <affiliation>Zhejiang Hospital</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Zhejiang Hospital</name>
        <address>
          <city>Hangzhou</city>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 18, 2023</study_first_submitted>
    <study_first_submitted_qc>September 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 5, 2023</study_first_posted>
    <last_update_submitted>September 1, 2023</last_update_submitted>
    <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 5, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Zhejiang Hospital</investigator_affiliation>
      <investigator_full_name>Pengyuan Liu</investigator_full_name>
      <investigator_title>Research Secretary</investigator_title>
    </responsible_party>
    <keyword>hyperthermia</keyword>
    <keyword>immune checkpoint inhibitor</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Digestive System Neoplasms</mesh_term>
      <mesh_term>Gastrointestinal Neoplasms</mesh_term>
      <mesh_term>Hyperthermia</mesh_term>
      <mesh_term>Fever</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Tislelizumab</mesh_term>
      <mesh_term>Immune Checkpoint Inhibitors</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06022692
  org study id: ZhejiangH
  nct id: NCT06022692
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  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.
  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.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: disease control rate (DCR)
  time frame: up to 6 months
  description: DCR=(PR+CR) / (PD+SD+PR+CR) * 100%
  measure: progression-free survival (PFS)
  time frame: up to 36 months
  description: The time between enrollment and tumor progression (in any aspect) or death (for any reason).
  measure: overall survival (OS)
  time frame: up to 36 months
  description: The time between enrollment and death (for any reason).
  arm group label: hyperthermia combined with immune checkpoint inhibitor group
  arm group type: Experimental
  description: 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).
  intervention type: Device
  intervention name: Water-filtered infrared A radiation whole-body hyperthermia (HECKEL 3000MT-4T, Germany)
  description: 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).
  arm group label: hyperthermia combined with immune checkpoint inhibitor group
  intervention type: Drug
  intervention name: tislelizumab (BeiGene, China) combined with PD-1 inhibitor
  description: 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).
  arm group label: hyperthermia combined with immune checkpoint inhibitor group
  other name: Immune checkpoint inhibitor
  other name: PD-1 antibody
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Jun Chen
  role: Study Director
  affiliation: Zhejiang Hospital
  facility: 
  country: China
  responsible party type: Sponsor-Investigator
  investigator affiliation: Zhejiang Hospital
  investigator full name: Pengyuan Liu
  investigator title: Research Secretary
  mesh term: Digestive System Neoplasms
  mesh term: Gastrointestinal Neoplasms
  mesh term: Hyperthermia
  mesh term: Fever
  mesh term: Tislelizumab
  mesh term: Immune Checkpoint Inhibitors
  sharing ipd: No