RadiotherapyPhase 2ILDR-02NCT07071103
Intestinal Low Dose Radiotherapy Combined With Immunotherapy in Immune-resistant Metastatic Malignant Solid Tumors
A Phase 2 study testing Low-dose radiotherapy to the intestine (ILDR) and PD-1/PD-L1 monoclonal antibodies in people with Radiotherapy and Metastatic Solid Cancers, run by Chuangzhen Chen at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Radiotherapy, Metastatic Solid Cancers, Immune Checkpoint Blockade
- What is being tested?
- Low-dose radiotherapy to the intestine (ILDR) and PD-1/PD-L1 monoclonal antibodies
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteChina
- Study dates
- 26 Sep 2025to 1 Jan 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 11Show fewer
- 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.
Who cannot join
- Patients with contraindications to radiation therapy and immunotherapy.
- Previous occurrence of unacceptable immune related toxic side effects (immune myocarditis, pneumonia, etc.).
- Patients who were assessed as hyperprogressive disease (HPD).
- 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).
- Patients with active uncontrolled systemic bacterial, viral, or fungal infections despite optimal treatment.
Show all 16Show fewer
- Significant liver or kidney dysfunction (i.e., laboratory values >3 times the upper limit of normal).
- 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.
- Drug and/or alcohol abuse.
- Pregnant or breastfeeding women.
- Concurrent participation in another therapeutic clinical trial.
- Poorly controlled pleural effusion, pericardial effusion, or ascites requiring frequent drainage (recurrence within ≤14 days after intervention).
- Major surgery within 30 days.
- Use of antibiotics, antifungals, antivirals, antiparasitics, or probiotics within 4 weeks before enrollment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Cancer Hospital, Shantou University Medical College
Shantou, Guangdong, 515031
Chuangzhen Chen
About this study
Official title: 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
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.
Read more
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.
- Conditions
- Radiotherapy, Metastatic Solid Cancers, Immune Checkpoint Blockade, Esophageal Neoplasms Malignant, Lung Neoplasm Malignant, Drug Resistance
- Being tested
- Low-dose radiotherapy to the intestine (ILDR), PD-1/PD-L1 monoclonal antibodies
- Medical subject headings
- Esophageal Neoplasms, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-dose radiotherapy to the intestine (ILDR)Radiation
A single total dose of 1 Gy irradiation targeting the jejunum and ileum. Primary tumor or metastatic lesions that are within the irradiation field are irradiated concurrently.
PD-1/PD-L1 monoclonal antibodiesDrug
Pre-progression immunotherapy regimen continues or switches to an alternative PD-1/PD-L1 monoclonal antibody according to clinical guidelines.PD-1/PD-L1 monoclonal antibody will be given 1 day after ILDR at a 3-week interval.
| Study group | Role | What they receive |
|---|---|---|
| Lung cancer arm | Experimental | This arm includes patients with metastatic non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) who have progressed after previous immune checkpoint blockades (ICBs) administration, and the intervention involves 1Gy/1F ILDR plus PD-1/PD-L1 inhibitors. Receives: Radiation: Low-dose radiotherapy to the intestine (ILDR); Drug: PD-1/PD-L1 monoclonal antibodies |
| Esophageal cancer group | Experimental | This arm includes patients with metastatic esophageal cancer (including squamous cell carcinoma or adenocarcinoma) who have progressed after previous ICB administration, and the intervention involves 1Gy/1F ILDR plus PD-1/PD-L1 inhibitors. Receives: Radiation: Low-dose radiotherapy to the intestine (ILDR); Drug: PD-1/PD-L1 monoclonal antibodies |
| Other solid tumor group | Experimental | This arm includes patients with other malignant solid tumors except lung cancer and esophageal cancer who have progressed after previous ICB administration, and the intervention involves 1Gy/1F ILDR plus PD-1/PD-L1 inhibitors. Receives: Radiation: Low-dose radiotherapy to the intestine (ILDR); Drug: PD-1/PD-L1 monoclonal antibodies |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
Proportion of patients achieving complete response (CR) or partial response (PR) (sustained ≥4 weeks) per RECIST v1.1.
Measured: 6, 12, 24 weeks after ILDR initiation.
Disease Control Rate（DCR）
Proportion of patients with CR, PR, or stable disease (SD) per RECIST v1.1.
Measured: 6, 12, 24 weeks after ILDR initiation.
Progression Free Survival while Receiving ILDR combined Therapy (PFS2)
Time from ILDR treatment to second documented disease progression (assessed by investigator via PSA, imaging, symptom, or the combinations) or death from any cause.
Measured: 6, 12, 24 weeks after ILDR initiation.
Incidence of Abscopal Effect
Proportion of patients demonstrating tumor response in one or more non-irradiated lesions.
Measured: 6, 12, 24 weeks after ILDR initiation.
Secondary outcomes (3)
Overall Survival (OS)
Time from ILDR treatment initiation to death from any cause.
Measured: 24, 48 weeks after radiotherapy initiation.
Cancer-Specific Survival (CSS)
Time from ILDR treatment initiation to death due to cancer.
Measured: 24, 48 weeks after radiotherapy initiation.
Adverse Events
Proportion of patients with treatment-related adverse events as assessed by CTCAE v5.0.
Measured: 12, 24, 48 weeks after radiotherapy initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2025
- Study start26 Sep 2025
- Primary completion1 Jan 2028 (estimated)
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for RadiotherapyStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chuangzhen Chen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Chuangzhen Chen, Shantou University Medical College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07071103
- Sponsor's protocol ID
- SUMC-ILDR02
- Acronym
- ILDR-02
- Status last verified
- Nov 2025
- First submitted
- 9 Jul 2025
- Last updated
- 20 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07071103
- Acronym / sponsor ID
- ILDR-02 / SUMC-ILDR02
- Conditions
- Radiotherapy, Metastatic Solid Cancers, Immune Checkpoint Blockade, Esophageal Neoplasms Malignant, Lung Neoplasm Malignant, Drug Resistance
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Chuangzhen ChenUniversity, hospital or other
- Study start
- 26 Sep 2025 (actual)
- Primary completion
- 1 Jan 2028 (estimated)
- Study completion
- 1 Jan 2028 (estimated)
- First posted
- 17 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Lung cancer arm | Experimental | Radiation: Low-dose radiotherapy to the intestine (ILDR), Drug: PD-1/PD-L1 monoclonal antibodiesThis arm includes patients with metastatic non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) who have progressed after previous immune checkpoint blockades (ICBs) administration, and the intervention involves 1Gy/1F ILDR plus PD-1/PD-L1 inhibitors. |
| Esophageal cancer group | Experimental | Radiation: Low-dose radiotherapy to the intestine (ILDR), Drug: PD-1/PD-L1 monoclonal antibodiesThis arm includes patients with metastatic esophageal cancer (including squamous cell carcinoma or adenocarcinoma) who have progressed after previous ICB administration, and the intervention involves 1Gy/1F ILDR plus PD-1/PD-L1 inhibitors. |
| Other solid tumor group | Experimental | Radiation: Low-dose radiotherapy to the intestine (ILDR), Drug: PD-1/PD-L1 monoclonal antibodiesThis arm includes patients with other malignant solid tumors except lung cancer and esophageal cancer who have progressed after previous ICB administration, and the intervention involves 1Gy/1F ILDR plus PD-1/PD-L1 inhibitors. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (16 listed)
- Patients with contraindications to radiation therapy and immunotherapy.
- Previous occurrence of unacceptable immune related toxic side effects (immune myocarditis, pneumonia, etc.).
- Patients who were assessed as hyperprogressive disease (HPD).
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low-dose radiotherapy to the intestine (ILDR)A single total dose of 1 Gy irradiation targeting the jejunum and ileum. Primary tumor or metastatic lesions that are within the irradiation field are irradiated concurrently. | Radiation | Esophageal cancer group, Lung cancer arm, Other solid tumor group |
| PD-1/PD-L1 monoclonal antibodiesPre-progression immunotherapy regimen continues or switches to an alternative PD-1/PD-L1 monoclonal antibody according to clinical guidelines.PD-1/PD-L1 monoclonal antibody will be given 1 day after ILDR at a 3-week interval. | Drug | Esophageal cancer group, Lung cancer arm, Other solid tumor group |
Primary outcome
Objective Response Rate (ORR)
Time frame: 6, 12, 24 weeks after ILDR initiation.
Proportion of patients achieving complete response (CR) or partial response (PR) (sustained ≥4 weeks) per RECIST v1.1.
Disease Control Rate（DCR）
Time frame: 6, 12, 24 weeks after ILDR initiation.
Proportion of patients with CR, PR, or stable disease (SD) per RECIST v1.1.
Progression Free Survival while Receiving ILDR combined Therapy (PFS2)
Time frame: 6, 12, 24 weeks after ILDR initiation.
Time from ILDR treatment to second documented disease progression (assessed by investigator via PSA, imaging, symptom, or the combinations) or death from any cause.
Incidence of Abscopal Effect
Time frame: 6, 12, 24 weeks after ILDR initiation.
Proportion of patients demonstrating tumor response in one or more non-irradiated lesions.
3 secondary outcomes
Overall Survival (OS)
Time frame: 24, 48 weeks after radiotherapy initiation.
Cancer-Specific Survival (CSS)
Time frame: 24, 48 weeks after radiotherapy initiation.
Adverse Events
Time frame: 12, 24, 48 weeks after radiotherapy initiation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2025.
- Individual participant dataSharing planned: No
Related trials for Radiotherapy
RecruitingObservational study
Proton Re-irradiation in Patients With Recurrent or Second Primary Head and Neck Cancer , a Multicentre Phase II Single Arm Trial
Head & Neck Cancer
RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
Not yet recruitingPhase 2
Toripalimab and Lenvatinib With or Without SBRT Before Surgery for Non-Clear Cell Kidney Cancer
Nonmetastatic Locally Advanced Non-Clear Cell Renal Cell Carcinoma
RecruitingObservational study
A Study of Neurocognitive Tests and Questionnaires for People With Head and Neck Cancer Who Are Undergoing Radiation Therapy
Head and Neck Cancer
RecruitingPhase 2
SBRT With Immunotherapy and Atezo-Bev in HCC With Major Portal Vein Thrombosis
HCC
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Low-dose radiotherapy to the intestine (ILDR) and PD-1/PD-L1 monoclonal antibodies in people with Radiotherapy and Metastatic Solid Cancers, run by Chuangzhen Chen at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chuangzhen Chen, MD (+86 13923995569, czchen2@stu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: 6, 12, 24 weeks after ILDR initiation.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2025.