Hyperthermia Combined With Immune Checkpoint Inhibitor Therapy for Advanced Gastrointestinal Tumours

NCT ID: NCT06022692

Last Updated: 2023-09-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-01
• Study Completion Date: 2023-08-01

Brief 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.

Conditions

Gastrointestinal Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Water-filtered infrared A radiation whole-body hyperthermia (HECKEL 3000MT-4T, Germany)

Intervention Type: DEVICE

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).

tislelizumab (BeiGene, China) combined with PD-1 inhibitor

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: DEVICE

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).

Intervention Type: DRUG

Other Intervention Names

Immune checkpoint inhibitor; PD-1 antibody

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zhejiang Hospital

OTHER

Sponsor Role: collaborator

Pengyuan Liu

OTHER

Sponsor Role: lead

Responsible Party

Pengyuan Liu

Research Secretary

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jun Chen

Role: STUDY_DIRECTOR

Zhejiang Hospital

Locations

Zhejiang Hospital

Hangzhou, , China

Countries

China

Other Identifiers

ZhejiangH

Identifier Type: -

Identifier Source: org_study_id