[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100660283":3},{"organization":4,"outcomesModule":7,"designInfo":45,"detailedDescription":51,"studyPopulation":44,"armGroups":52,"interventions":61,"overallOfficials":82,"centralContacts":87,"locations":93,"responsibleParty":105,"collaborators":44,"id":107,"slug":108,"hasResults":109,"nctId":110,"briefTitle":111,"officialTitle":112,"acronym":113,"eligibilityCriteria":114,"healthyVolunteers":109,"sex":115,"minAge":116,"maxAge":44,"enrollmentInfo":117,"targetDuration":44,"studyType":120,"phases":121,"briefSummary":123,"conditions":124,"keywords":130,"overallStatus":138,"whyStopped":44,"lastUpdateSubmitDate":139,"lastUpdatePostDateStruct":140,"startDateStruct":143,"completionDateStruct":145,"leadSponsor":147,"locationsCount":148},{"fullName":5,"class":6},"First People's Hospital of Hangzhou","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":44},[9],{"measure":10,"description":11,"timeFrame":12},"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.",[14,17,21,25,29,33,37,41],{"measure":15,"description":16,"timeFrame":12},"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.",{"measure":18,"description":19,"timeFrame":20},"Disease Control Rate (DCR) of Liver Metastases","Proportion of patients achieving CR, PR, or stable disease (SD) in liver metastatic lesions.","At 6, 12, and 24 weeks after ILDR.",{"measure":22,"description":23,"timeFrame":24},"Overall Disease Control Rate (DCR)","Proportion of patients achieving CR, PR, or SD in all target lesions.","At 6, 12, 24 weeks and every 6 weeks thereafter, until disease progression, death, or up to 24 months.",{"measure":26,"description":27,"timeFrame":28},"Progression-Free Survival (PFS)","Time from the first day of treatment to disease progression or death from any cause, whichever occurs first.","From the first day of treatment to disease progression or death from any cause, whichever occurs first, assessed up to 36 months.",{"measure":30,"description":31,"timeFrame":32},"Overall Survival (OS)","Time from the first day of treatment to death from any cause.","Up to 3 years.",{"measure":34,"description":35,"timeFrame":36},"Incidence of Adverse Events (AEs)","Frequency and severity of adverse events graded according to CTCAE v5.0.","From informed consent to 30 days after the last dose.",{"measure":38,"description":39,"timeFrame":40},"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.","Baseline, 24-48 hours after ILDR, and Day 1 of each ICIs cycle (each cycle is 21 days).",{"measure":42,"description":43,"timeFrame":40},"Changes in Gut Microbiome and Metabolomics","Changes in gut microbiome composition (metagenomics) and metabolites (metabolomics) in stool samples.",null,{"allocation":46,"interventionModel":47,"interventionModelDescription":44,"primaryPurpose":48,"observationalModel":44,"timePerspective":44,"maskingInfo":49},"NA","SINGLE_GROUP","TREATMENT",{"masking":50,"maskingDescription":44,"whoMasked":44},"NONE","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.\n\nStudy 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\u002FPD-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\u002Fpancreatic 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.\n\nIntervention: Patients will receive ILDR (1 Gy\u002F1 fraction, IMRT\u002FVMAT) targeting the jejunum, ileum, and mesentery (Dmean = 1 Gy) on Day 1. ICIs (PD-1\u002FPD-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\u002FFOLFOX\u002FFOLFIRI\u002FAG for Cohort C.\n\nEndpoints: 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.\n\nStatistical 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.",[53],{"label":54,"type":55,"description":56,"interventionNames":57},"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\u002F1F) on Day 1. Immune checkpoint inhibitors (PD-1\u002FPD-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\u002FFOLFOX\u002FFOLFIRI\u002FAG for Cohort C (colorectal\u002Fpancreatic cancer).",[58,59,60],"Radiation: Intestinal Low-Dose Radiotherapy (ILDR)","Drug: PD-1\u002FPD-L1 inhibitors","Drug: Combined Chemotherapy",[62,69,76],{"type":63,"name":64,"description":65,"armGroupLabels":66,"otherNames":67},"RADIATION","Intestinal Low-Dose Radiotherapy (ILDR)","Single fraction of 1 Gy delivered to the intestine (jejunum, ileum, and mesentery) using IMRT\u002FVMAT.",[54],[68],"ILDR",{"type":70,"name":71,"description":72,"armGroupLabels":73,"otherNames":74},"DRUG","PD-1\u002FPD-L1 inhibitors","Administered 24-72 hours after ILDR, every 3 weeks, for up to 2 years.",[54],[75],"ICIs",{"type":70,"name":77,"description":78,"armGroupLabels":79,"otherNames":80},"Combined Chemotherapy","Regimens based on tumor type: docetaxel (Cohort A), platinum-based doublet (Cohort B), or XELOX\u002FFOLFOX\u002FFOLFIRI\u002FAG (Cohort C).",[54],[81],"Systemic Chemotherapy",[83],{"name":84,"affiliation":85,"role":86},"Bing Xia","Hangzhou Cancer Hospital","PRINCIPAL_INVESTIGATOR",[88],{"name":89,"role":90,"phone":91,"phoneExt":44,"email":92},"Bing Xia, MD.","CONTACT","+86-571-56005600","xb0918@hotmail.com",[94],{"facility":85,"status":44,"city":95,"state":96,"zip":44,"country":97,"countryCode":98,"cosmosGeoPoint":99,"geoPoint":104,"contacts":44},"Hangzhou","Zhejiang","China","CN",{"type":100,"coordinates":101},"Point",[102,103],120.16142,30.29365,{"lat":103,"lon":102},{"type":106,"investigatorFullName":84,"investigatorTitle":85,"investigatorAffiliation":5,"oldNameTitle":44,"oldOrganization":44},"SPONSOR_INVESTIGATOR","100660283","phase-2-intestinal-low-dose-radiotherapy-combined-with-immune-checkpoint-inhibitors-in-solid-tumors-with-liver-metastases-100660283",false,"NCT07875465","Intestinal Low-Dose Radiotherapy Combined With Immune Checkpoint Inhibitors in Solid Tumors With Liver Metastases","Intestinal Low-Dose Radiotherapy Combined With Immune Checkpoint Inhibitors in the Treatment of Liver Metastases From Solid Tumors: A Prospective Cohort Study","ILDR-ICI-LM","Inclusion Criteria:\n\n* Age ≥ 18 years, male or female.\n* ECOG performance status 0-2.\n* Expected survival ≥ 3 months.\n* Histologically or cytologically confirmed advanced solid malignancies:\n\n  * Cohort A: Advanced NSCLC with negative driver genes (EGFR\u002FALK\u002FROS1), disease progression during first-line platinum-based doublet chemotherapy combined with PD-1\u002FPD-L1 inhibitors.\n  * Cohort B: Advanced NSCLC with positive driver genes (EGFR\u002FALK\u002FROS1), disease progression during first-line targeted therapy.\n  * Cohort C: Advanced colorectal or pancreatic cancer, disease progression during no more than two lines of therapy.\n* Confirmed liver metastasis (pathologically or by 2 imaging modalities).\n* At least 1 measurable intrahepatic target lesion per RECIST v1.1.\n* Brain metastases are permitted if radiologically stable.\n* Adequate major organ function within 7 days prior to enrollment:\n\n  * Hematology: Absolute neutrophil count ≥ 1.5 × 10\\^9\u002FL, Platelets ≥ 100 × 10\\^9\u002FL, Hemoglobin ≥ 90 g\u002FL.\n  * Liver: Total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for Gilbert's syndrome or liver metastasis); AST\u002FALT ≤ 2.5 × ULN (≤ 5 × ULN for liver metastasis).\n  * Kidney: Serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL\u002Fmin (Cockcroft-Gault formula).\n\nExclusion Criteria:\n\n* Contraindications to radiotherapy and immune checkpoint inhibitor therapy.\n* Prior unacceptable toxicity following immune checkpoint inhibitor therapy.\n* History of abdominopelvic radiotherapy within 6 months prior to enrollment.\n* Prior anti-tumor adverse events not recovered to CTCAE 5.0 Grade ≤ 1.\n* Active uncontrolled systemic bacterial, viral, or fungal infection.\n* Use of antibiotics, antifungals, antivirals, or antiparasitics within 2 weeks prior to enrollment.\n* Any lesion burden with a maximum diameter \\> 4 cm.\n* Other standard exclusion criteria (e.g., pregnancy, lactation, severe comorbidities, etc.).","ALL","18 Years",{"count":118,"type":119},120,"ESTIMATED","INTERVENTIONAL",[122],"PHASE2","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.\n\nLiver 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.\n\nThis 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.\n\nThe 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.",[125,126,127,128,129],"Liver Metastases","Non-Small Cell Lung Cancer","Colorectal Cancer (Diagnosis)","Pancreatic Cancer Metastatic","Solid Tumors",[131,68,132,133,134,135,136,137,129],"Intestinal Low-Dose Radiotherapy","Immune Checkpoint Inhibitors","PD-1\u002FPD-L1","Liver Metastasis","Immunotherapy Resistance","Gut Microbiome","Prospective Cohort Study","NOT_YET_RECRUITING","2026-10-08",{"date":141,"type":142},"2026-10-15","ACTUAL",{"date":144,"type":119},"2026-10",{"date":146,"type":119},"2031-04",{"name":84,"class":6},1]