Intestinal Low-Dose Radiotherapy Combined With Immune Checkpoint Inhibitors in Solid Tumors With Liver Metastases

NCT07875465 | Not Yet Recruiting Phase 2

• 2 other identifiers: HZCH-ILDR-ICI-LM-001HZCH-2026-004
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the effectiveness and safety of combining low-dose radiotherapy to the intestines with immune checkpoint inhibitors (ICIs) in patients with liver metastases from solid tumors. Liver metastases often create an "immune desert" that makes immunotherapy less effective. Recent research has shown that low-dose irradiation of the gut (1 Gy) can reshape the gut microbiome and activate the immune system, potentially reversing resistance to immunotherapy. This is a prospective, single-arm, single-center cohort study. We plan to enroll 120 patients with liver metastases from non-small cell lung cancer (NSCLC), colorectal cancer, or pancreatic cancer. All participants will receive a single low dose of radiotherapy to the intestine (1 Gy), followed by standard immune checkpoint inhibitors and chemotherapy. The main goal of this study is to see how well the liver metastases respond to this combined treatment. We will also monitor survival, side effects, and changes in the gut bacteria and blood immune markers to understand how this treatment works. This strategy may provide a low-cost, low-toxicity new option for patients whose liver metastases have stopped responding to standard immunotherapy.

Conditions

Liver Metastases; Non-Small Cell Lung Cancer; Colorectal Cancer (Diagnosis); Pancreatic Cancer Metastatic; Solid Tumors

Keywords

Intestinal Low-Dose Radiotherapy; ILDR; Immune Checkpoint Inhibitors; PD-1/PD-L1; Liver Metastasis; Immunotherapy Resistance; Gut Microbiome; Prospective Cohort Study; Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) of Liver Metastases

  Proportion of patients achieving complete response (CR) or partial response (PR) in liver metastatic lesions, as assessed by RECIST v1.1.

  Every 6 weeks (± 3 days) until disease progression, death, or up to 24 months.

Secondary Outcomes (8)

• Overall Objective Response Rate (ORR)

  Every 6 weeks (± 3 days) until disease progression, death, or up to 24 months.

• Disease Control Rate (DCR) of Liver Metastases

  At 6, 12, and 24 weeks after ILDR.

• Overall Disease Control Rate (DCR)

  At 6, 12, 24 weeks and every 6 weeks thereafter, until disease progression, death, or up to 24 months.

• Progression-Free Survival (PFS)

  From the first day of treatment to disease progression or death from any cause, whichever occurs first, assessed up to 36 months.

• Overall Survival (OS)

  Up to 3 years.

Study Arms (1)

ILDR Combined With ICIs and Chemotherapy

EXPERIMENTAL

Patients with liver metastases from solid tumors receive a single fraction of intestinal low-dose radiotherapy (ILDR, 1 Gy/1F) on Day 1. Immune checkpoint inhibitors (PD-1/PD-L1) are administered 24-72 hours after ILDR, every 3 weeks, for up to 2 years. Combined chemotherapy is given based on tumor type: docetaxel for Cohort A (NSCLC driver gene negative), platinum-based doublet for Cohort B (NSCLC driver gene positive), and XELOX/FOLFOX/FOLFIRI/AG for Cohort C (colorectal/pancreatic cancer).

Radiation: Intestinal Low-Dose Radiotherapy (ILDR); Drug: PD-1/PD-L1 inhibitors; Drug: Combined Chemotherapy

Interventions

Intestinal Low-Dose Radiotherapy (ILDR) RADIATION

Single fraction of 1 Gy delivered to the intestine (jejunum, ileum, and mesentery) using IMRT/VMAT.

Also known as: ILDR

ILDR Combined With ICIs and Chemotherapy

PD-1/PD-L1 inhibitors DRUG

Administered 24-72 hours after ILDR, every 3 weeks, for up to 2 years.

Also known as: ICIs

ILDR Combined With ICIs and Chemotherapy

Combined Chemotherapy DRUG

Regimens based on tumor type: docetaxel (Cohort A), platinum-based doublet (Cohort B), or XELOX/FOLFOX/FOLFIRI/AG (Cohort C).

Also known as: Systemic Chemotherapy

ILDR Combined With ICIs and Chemotherapy

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years, male or female.
• ECOG performance status 0-2.
• Expected survival ≥ 3 months.
• Histologically or cytologically confirmed advanced solid malignancies:
• Cohort A: Advanced NSCLC with negative driver genes (EGFR/ALK/ROS1), disease progression during first-line platinum-based doublet chemotherapy combined with PD-1/PD-L1 inhibitors.
• Cohort B: Advanced NSCLC with positive driver genes (EGFR/ALK/ROS1), disease progression during first-line targeted therapy.
• Cohort C: Advanced colorectal or pancreatic cancer, disease progression during no more than two lines of therapy.
• Confirmed liver metastasis (pathologically or by 2 imaging modalities).
• At least 1 measurable intrahepatic target lesion per RECIST v1.1.
• Brain metastases are permitted if radiologically stable.
• Adequate major organ function within 7 days prior to enrollment:
• Hematology: Absolute neutrophil count ≥ 1.5 × 10\^9/L, Platelets ≥ 100 × 10\^9/L, Hemoglobin ≥ 90 g/L.
• Liver: Total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for Gilbert's syndrome or liver metastasis); AST/ALT ≤ 2.5 × ULN (≤ 5 × ULN for liver metastasis).
• Kidney: Serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula).

You may not qualify if:

• Contraindications to radiotherapy and immune checkpoint inhibitor therapy.
• Prior unacceptable toxicity following immune checkpoint inhibitor therapy.
• History of abdominopelvic radiotherapy within 6 months prior to enrollment.
• Prior anti-tumor adverse events not recovered to CTCAE 5.0 Grade ≤ 1.
• Active uncontrolled systemic bacterial, viral, or fungal infection.
• Use of antibiotics, antifungals, antivirals, or antiparasitics within 2 weeks prior to enrollment.
• Any lesion burden with a maximum diameter \> 4 cm.

Sponsors & Collaborators

• Bing Xia: lead

Study Sites (1)

Hangzhou Cancer Hospital

Hangzhou, Zhejiang, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Disease

Interventions

Radiotherapy; Immune Checkpoint Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Antineoplastic Protocols; Clinical Protocols; Drug Therapy; Drug Therapy, Combination; Combined Modality Therapy

Study Officials

• Bing Xia

  Hangzhou Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bing Xia, MD.

CONTACT

+86-571-56005600; xb0918@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Hangzhou Cancer Hospital

Study Record Dates

• First Submitted: September 27, 2026
• First Posted: October 15, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2031
• Last Updated: October 15, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)