Liver MetastasesPhase 2ILDR-ICI-LMNCT07875465
Intestinal Low-Dose Radiotherapy Combined With Immune Checkpoint Inhibitors in Solid Tumors With Liver Metastases
A Phase 2 study testing Intestinal Low-Dose Radiotherapy (ILDR), PD-1/PD-L1 inhibitors and Combined Chemotherapy in people with Liver Metastases and Non-Small Cell Lung Cancer, run by Bing Xia at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Metastases, Non-Small Cell Lung Cancer, Colorectal Cancer (Diagnosis)
- What is being tested?
- Intestinal Low-Dose Radiotherapy (ILDR), PD-1/PD-L1 inhibitors and Combined Chemotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteChina
- Study dates
- Oct 2026to Apr 2031
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- 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.
- Other standard exclusion criteria (e.g., pregnancy, lactation, severe comorbidities, etc.).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Intestinal Low-Dose Radiotherapy Combined With Immune Checkpoint Inhibitors in the Treatment of Liver Metastases From Solid Tumors: A Prospective Cohort Study
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.
Read more
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.
Read the detailed description
Background: Liver metastasis is a common cause of death in advanced solid tumors and is associated with systemic immune suppression, leading to primary resistance to immune checkpoint inhibitors (ICIs). Preclinical and clinical evidence suggests that low-dose irradiation of the gut (ILDR, 1-3 Gy) can induce the migration of regulatory dendritic cells (mregDCs) from mesenteric lymph nodes to tumor-draining lymph nodes, cross-activate CD8+ T cells, and reprogram metabolism, thereby synergizing with ICIs. The Chen et al. (Cancer Cell 2025) study demonstrated that ILDR (1-3 Gy) significantly improved overall survival in patients receiving SABR plus anti-PD-L1, with an inverted U-shaped dose-response relationship. This study aims to prospectively evaluate the efficacy and safety of ILDR combined with ICIs in patients with liver metastases from solid tumors.
Study Design: This is a prospective, single-arm, single-center, exploratory cohort study. A one-sided exact binomial test will be used to compare the liver metastasis ORR with historical controls. The study plans to enroll 120 patients in three cohorts: Cohort A (NSCLC, driver gene negative, after first-line platinum-based chemotherapy plus PD-1/PD-L1 inhibitor progression, expected ORR 30% vs 10%), Cohort B (NSCLC, driver gene positive, after first-line targeted therapy progression, expected ORR 55% vs 35%), and Cohort C (colorectal/pancreatic cancer, after up to two lines of therapy progression, expected ORR 35% vs 15%). A two-stage execution rule with futility analysis will be applied.
Intervention: Patients will receive ILDR (1 Gy/1 fraction, IMRT/VMAT) targeting the jejunum, ileum, and mesentery (Dmean = 1 Gy) on Day 1. ICIs (PD-1/PD-L1 inhibitors) will be administered 24-72 hours after ILDR, every 3 weeks, for up to 2 years. Combined chemotherapy regimens include docetaxel for Cohort A, platinum-based doublet for Cohort B, and XELOX/FOLFOX/FOLFIRI/AG for Cohort C.
Endpoints: The primary endpoint is liver metastasis objective response rate (ORR) per RECIST v1.1. Secondary endpoints include overall ORR, disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety (CTCAE 5.0), and multi-omics analysis (gut microbiome, metabolomics, immune profiling) of peripheral blood and stool samples.
Statistical Analysis: The primary endpoint will be analyzed using the Clopper-Pearson exact method for 95% CI. PFS and OS will be estimated using the Kaplan-Meier method. Multi-omics data will be analyzed using Wilcoxon signed-rank test, Mann-Whitney U test, LEfSe, PLS-DA, and Spearman correlation analysis.
- Conditions
- Liver Metastases, Non-Small Cell Lung Cancer, Colorectal Cancer (Diagnosis), Pancreatic Cancer Metastatic, Solid Tumors
- Being tested
- Intestinal Low-Dose Radiotherapy (ILDR), PD-1/PD-L1 inhibitors, Combined Chemotherapy
- Keywords
- Intestinal Low-Dose Radiotherapy, ILDR, Immune Checkpoint Inhibitors, PD-1/PD-L1, Liver Metastasis, Immunotherapy Resistance, Gut Microbiome, Prospective Cohort Study, Solid Tumors
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intestinal Low-Dose Radiotherapy (ILDR)Radiation
Also called ILDR
Single fraction of 1 Gy delivered to the intestine (jejunum, ileum, and mesentery) using IMRT/VMAT.
PD-1/PD-L1 inhibitorsDrug
Also called ICIs
Administered 24-72 hours after ILDR, every 3 weeks, for up to 2 years.
Combined ChemotherapyDrug
Also called Systemic Chemotherapy
Regimens based on tumor type: docetaxel (Cohort A), platinum-based doublet (Cohort B), or XELOX/FOLFOX/FOLFIRI/AG (Cohort C).
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Radiation: Intestinal Low-Dose Radiotherapy (ILDR); Drug: PD-1/PD-L1 inhibitors; Drug: Combined Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Every 6 weeks (± 3 days) until disease progression, death, or up to 24 months.
Secondary outcomes (8)
Overall Objective Response Rate (ORR)
Proportion of patients achieving complete response (CR) or partial response (PR) in all target lesions, assessed by RECIST v1.1.
Measured: Every 6 weeks (± 3 days) until disease progression, death, or up to 24 months.
Disease Control Rate (DCR) of Liver Metastases
Proportion of patients achieving CR, PR, or stable disease (SD) in liver metastatic lesions.
Measured: At 6, 12, and 24 weeks after ILDR.
Overall Disease Control Rate (DCR)
Proportion of patients achieving CR, PR, or SD in all target lesions.
Measured: At 6, 12, 24 weeks and every 6 weeks thereafter, until disease progression, death, or up to 24 months.
Progression-Free Survival (PFS)
Time from the first day of treatment to disease progression or death from any cause, whichever occurs first.
Measured: 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)
Time from the first day of treatment to death from any cause.
Measured: Up to 3 years.
Incidence of Adverse Events (AEs)
Frequency and severity of adverse events graded according to CTCAE v5.0.
Measured: From informed consent to 30 days after the last dose.
Changes in Peripheral Blood Immune Landscape, Transcriptomics, and Metabolomics
Changes in immune cell subsets, gene transcription profiles, immune receptor repertoire, metabolomics, and cytokines in peripheral blood.
Measured: Baseline, 24-48 hours after ILDR, and Day 1 of each ICIs cycle (each cycle is 21 days).
Changes in Gut Microbiome and Metabolomics
Changes in gut microbiome composition (metagenomics) and metabolites (metabolomics) in stool samples.
Measured: Baseline, 24-48 hours after ILDR, and Day 1 of each ICIs cycle (each cycle is 21 days).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2026
- Study startOct 2026 (estimated)
- Primary completionApr 2029 (estimated)
- Study completionApr 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver MetastasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bing Xia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Bing Xia, First People's Hospital of Hangzhou
- Investigators
- Bing Xia, Principal investigator, Hangzhou Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07875465
- Sponsor's protocol ID
- HZCH-ILDR-ICI-LM-001
- Other IDs
- HZCH-2026-004
- Acronym
- ILDR-ICI-LM
- Status last verified
- Oct 2026
- First submitted
- 27 Sep 2026
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No