Hyperthermia Combined With Immune Checkpoint Inhibitors in the Treatment of Advanced Gastrointestinal Malignancies With Liver Metastases

NCT07118566 | Not Yet Recruiting Phase 2

• 1 other identifier: CLOG-2025GI-HT01
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study aims to explore the synergistic antitumor effects and safety of hyperthermia combined with immune checkpoint inhibitors (ICIs) in patients with advanced gastrointestinal malignancies with liver metastases. Liver metastasis represents a common cause of treatment failure in gastrointestinal cancers, and the response rate to ICIs remains suboptimal in certain patients with liver metastases, potentially attributable to the immunosuppressive hepatic microenvironment. The combination of hyperthermia with ICIs, chemotherapy, or other therapeutic modalities may further enhance treatment efficacy. Hyperthermia could potentially reverse immunosuppression and improve ICI effectiveness through mechanisms including enhanced tumor blood perfusion, promoted antigen presentation, and increased immune cell infiltration. This multicenter, open-label, dual-cohort phase II trial will evaluate patients stratified by tumor type (colorectal cancer versus gastric cancer) to assess the objective response rate (ORR), progression-free survival (PFS), and safety profile of hyperthermia-ICI combination therapy. Concurrently, dynamic monitoring of peripheral immune markers (such as neutrophil-to-lymphocyte ratio and interleukins) and tumor microenvironment alterations will be conducted to identify potential predictive biomarkers, thereby providing preliminary evidence for subsequent phase III investigations. The ultimate objective is to develop more effective combination treatment strategies for patients with advanced gastrointestinal malignancies accompanied by liver metastases.

Conditions

Gastrointestinal Cancer; Immunotherapy; Liver Metastasis

Keywords

gastrointestinal cancer; immunotherapy; liver metastasis; hyperthermia

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Objective response rate (ORR) refers to the proportion of patients whose tumor volume has shrunk to the pre-specified value and can maintain the minimum duration requirement (at least 4 weeks, assessed up to 12 months) by the RECIST (Version 1.1), which is the sum of the proportions of complete response (CR) and partial response (PR).

  From the start of treatment to tumor progression or death from any cause (whichever occurs first, at least 4 weeks, assessed up to 12 months).

Secondary Outcomes (3)

• Progression Free Survival

  Progression-free survival (PFS) refers to the time from the start of treatment to tumor progression or death from any cause (whichever occurs first, at least 4 weeks, assessed up to 12 months).

• Disease Control Rate

  From the start of treatment to tumor progression or death from any cause (whichever occurs first, at least 4 weeks, assessed up to 12 months).

• Overall Survival

  From study enrollment through 12 months post-treatment completion of the last participant.

Study Arms (2)

Cohort 1: gastric cancer

EXPERIMENTAL

Gastric cancer patients must have received at least one prior line of systemic therapy.

Procedure: Hyperthermia; Drug: Immunotherapy

Cohort 2: colorectal cancer

EXPERIMENTAL

Colorectal cancer patients must have received at least two prior lines of systemic therapy.

Procedure: Hyperthermia; Drug: Immunotherapy

Interventions

Hyperthermia PROCEDURE

Each session of hyperthermia should be spaced at least 24 hours apart, with at least one session administered prior to ICI (immune checkpoint inhibitor) treatment. Five times q3w.

Also known as: Microwave hyperthermia

Cohort 1: gastric cancer; Cohort 2: colorectal cancer

Immunotherapy DRUG

iv，d1，q3w

Cohort 1: gastric cancer; Cohort 2: colorectal cancer

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 75 years, male or female.
• Histologically or cytologically confirmed diagnosis of gastrointestinal malignancy with liver metastases.
• Prior treatment requirements:
• Gastric cancer patients must have received at least one prior line of systemic therapy.
• Colorectal cancer patients must have received at least two prior lines of systemic therapy.
• Clinically assessed as suitable for hyperthermia combined with immune checkpoint inhibitor therapy.
• At least one measurable lesion meeting RECIST 1.1 criteria.
• Expected survival ≥6 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Adequate organ and bone marrow function.
• Willingness to provide sufficient baseline and post-treatment samples, ability to comply with long-term follow-up and evaluation, and signed informed consent.
• No prior history of other malignancies.

You may not qualify if:

• Pregnant or lactating women.
• Any comorbidities or underlying medical conditions that, in the investigator's judgment, render the patient unsuitable for study participation.

Sponsors & Collaborators

• China Medical University, China: lead

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Hyperthermia

Interventions

Diathermy; Immunotherapy

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heat Stress Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Hyperthermia, Induced; Therapeutics; Immunomodulation; Biological Therapy

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: July 28, 2025
• First Posted: August 12, 2025
• Study Start: August 15, 2025
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: August 12, 2025

Record last verified: 2025-05