Hyperthermia Combined With Immune Checkpoint Inhibitor Therapy for Advanced Gastrointestinal Tumours (HEAIS001)

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

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.

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Tumor
• Intervention / Treatment: Device: Water-filtered infrared A radiation whole-body hyperthermia (HECKEL 3000MT-4T, Germany); Drug: tislelizumab (BeiGene, China) combined with PD-1 inhibitor

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Hangzhou, China
    • Zhejiang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with advanced GIT who have previously received third-line or above treatment.
• Patients are aged 18-75.
• Patients with at least one measurable tumor lesion.
• Patients' all physiological indexes meet the HIT requirements.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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).

Device: Water-filtered infrared A radiation whole-body hyperthermia (HECKEL 3000MT-4T, Germany); 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).; Drug: tislelizumab (BeiGene, China) combined with PD-1 inhibitor; 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 Names: Immune checkpoint inhibitor; PD-1 antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disease control rate (DCR)	DCR=(PR+CR) / (PD+SD+PR+CR) * 100%	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival (PFS)	The time between enrollment and tumor progression (in any aspect) or death (for any reason).	up to 36 months
overall survival (OS)	The time between enrollment and death (for any reason).	up to 36 months

Collaborators and Investigators

• Sponsor: Pengyuan Liu
• Collaborators: Zhejiang Hospital
• Investigators: Study Director: Jun Chen, Zhejiang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): May 31, 2022
• Study Completion (Actual): August 1, 2023

Study Registration Dates

• First Submitted: August 18, 2023
• First Submitted That Met QC Criteria: September 1, 2023
• First Posted (Actual): September 5, 2023

Study Record Updates

• Last Update Posted (Actual): September 5, 2023
• Last Update Submitted That Met QC Criteria: September 1, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: hyperthermia; immune checkpoint inhibitor
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Wounds and Injuries; Gastrointestinal Diseases; Body Temperature Changes; Heat Stress Disorders; Gastrointestinal Neoplasms; Digestive System Neoplasms; Hyperthermia; Fever; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Tislelizumab
• Other Study ID Numbers: ZhejiangH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No