NCT07071103RecruitingPhase 2

Intestinal Low Dose Radiotherapy Combined With Immunotherapy in Immune-resistant Metastatic Malignant Solid Tumors

Efficacy and Safety of Combining Intestinal Low Dose Radiotherapy and PD-1/PD-L1 Inhibitors for Metastatic Malignant Solid Tumors After Acquired Resistance to Anti-PD1/PD-L1 Treatment

Source: ClinicalTrials.gov · Last updated 20 Nov 2025

Brief summary (registry, in English)

Preclinical and clinical evidence suggests that intestinal low-dose radiotherapy (ILDR) may enhance antitumor immune responses by modulating the gut microenvironment, thereby improving the efficacy of immune checkpoint inhibitors (ICBs) in refractory solid tumors. Based on these findings, the investigators initiate a multicohort phase II clinical trial to evaluate the clinical benefit and safety of ILDR combined with PD-1/PD-L1 monoclonal antibody therapy in patients with metastatic solid tumors resistant to prior ICB treatment. In this study, patients are stratified into three parallel cohorts by tumor type (lung cancer, esophageal cancer, and other solid tumors), with 16 patients per cohort (48 in total, including subjects enrolled from the ILDR-01 study). Eligible participants includes patients with advanced metastatic solid tumors progressing after monotherapy or combination ICB treatment, meeting criteria of ECOG performance status 0-2, life expectancy ≥3 months, and have at least one measurable lesion. Exclusion criteria encompasses prior pelvic radiotherapy, ongoing infections, major organ dysfunction, or concurrent antitumor therapies. The primary endpoints includes objective response rate (ORR), disease control rate (DCR), progression-free survival after ILDR (PFS2), and the incidence of abscopal effects. Secondary endpoints includes overall survival (OS), treatment safety, α/β diversity changes in gut microbiota, peripheral blood immune cell subset dynamics, and tumor immune microenvironment remodeling characteristics. All patients receives a 1 Gy jejunoileal radiotherapy followed by PD-1/PD-L1 monoclonal antibody administration (in accordance to prior protocols or guidelines) within 24 hours, with maintenance therapy up to 2 years. Therapeutic efficacy is assessed via RECIST v1.1, while therapeutic toxicity is assessed according to CTCAE v5.0. Paired pre- and post-treatment samples (including wumor tissue, stool, peripheral blood etc.) are collected for metagenomic sequencing, metabolomic analysis, and multi-omics integrative modeling to systematically elucidate the regulation mechanism of gut microbiota-metabolite-immune axis mediated by ILDR. This approach aims to provide theoretical foundations for optimizing treatment strategies in immunotherapy-resistant tumors and identify biomarkers that potentially associated with therapeutic efficacy.

Status (registry): Recruiting
Phase (registry): Phase 2
Study type: Interventional
Enrollment: 48 (estimated)
First submitted: 9 Jul 2025
Start date: 26 Sept 2025
Primary completion date: 1 Jan 2028
Lead sponsor: Chuangzhen Chen
Diseases: Lung cancer, Gastric and esophageal cancer
NCT number: NCT07071103

What you commit to

Study type: Interventional · Phase 2
Planned participants: 48
From 26 Sept 2025 to the primary completion date, 1 Jan 2028
1 site in 1 country
Visits and tests: ask the trial team, the registry does not list them

Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.

Who cannot take part

Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.

Prior treatment

Patients with contraindications to radiation therapy and immunotherapy.
Previous occurrence of unacceptable immune related toxic side effects (immune myocarditis, pneumonia, etc.).
Patients who have received pelvic and abdominal radiation therapy within 6 months prior to enrollment.
The adverse reactions from prior treatment have not yet recovered to a CTCAE5.0 rating of ≤ 1 (excluding toxicity that has been determined to be risk-free, such as fatigue or hair loss).
Drug and/or alcohol abuse.
Concurrent participation in another therapeutic clinical trial.
Major surgery within 30 days.
Use of antibiotics, antifungals, antivirals, antiparasitics, or probiotics within 4 weeks before enrollment.

Other illness

Patients who were assessed as hyperprogressive disease (HPD).
Patients with active uncontrolled systemic bacterial, viral, or fungal infections despite optimal treatment.
Active hepatitis B, hepatitis C, HIV, or syphilis.
Brain disorders, symptomatic central nervous system (CNS) or meningeal metastases, or impaired cognitive function.
Hypersensitivity to any drug included in the trial.

Lab values

Significant liver or kidney dysfunction (i.e., laboratory values \>3 times the upper limit of normal).

Other

Pregnant or breastfeeding women.
Poorly controlled pleural effusion, pericardial effusion, or ascites requiring frequent drainage (recurrence within ≤14 days after intervention).

Who the study is looking for

Age ≥18 years, ≤80 years, regardless of gender.
ECOG level 0-2.
Expected life span\>3 months.
At least one accessible and measurable lesion should be selected as the target lesion for observation according to RECIST criteria.
Patients with metastatic solid tumors (of any histology) without standard therapy options, who have previously received immunotherapy, immunotherapy combined with chemotherapy, or immunotherapy combined with anti-angiogenesis treatment and have shown disease progression.
Patients should not be considered eligible for surgical treatment.
Patients with brain metastases that are assessed as clinically stable after treatment through repeated CT and/or MRI scans are eligible.
Patients have complete clinical and pathological information.
Patients should not be borthered by any psychological, family, social or geographical conditions that may hinder compliance with the research protocol.
Patients should be able to understand the informed consent form, voluntarily participate, and sign the informed consent form.
Other indicators accord with the general inclusion criteria for clinical trials.

Age in the registry: 18 years to 80 years · Sex: All · Does not accept healthy volunteers

Full criteria on ClinicalTrials.gov

Sites (1)

Sites in registry order. Pick your city on the disease page to sort them by distance.

Site	City	Country	Site status
Cancer Hospital, Shantou University Medical College Coordinator of this site? Confirm its status	Shantou	China	Recruiting

This page is information, not medical advice. Discuss any trial with your doctor.