Safety and Efficacy of Radiotherapy Combined with Immunotherapy for Advanced Malignant Tumors.

Phase 1

Recruiting

• Conditions: Advanced Solid Tumor
• Interventions: Combination Product: Radiotherapy combined with immunotherapy

• Registration Number: NCT06173219
• Lead Sponsor: China-Japan Friendship Hospital

Brief Summary

The goal of this clinical trial is to find a new radioimmunotherapy regimen for advanced malignancies with multiple metastatic after standard treatment failure/drug resistance. The main questions it aims to answer is: the safety and efficacy of the new regimen for advanced multiple metastatic solid tumors standard treatment failure/drug resistance, and explore the impact on immune function. Participants will receive the combination of radiotherapy and immunotherapy.

Detailed Description

More effective treatment regimens remain to be explored for advanced malignancies with multiple metastatic after standard treatment failure/drug resistance. The combination of radiotherapy and immunotherapy is considered to be a promising therapeutic strategy. Studies showed the efficacy of PRaG (PD-1 inhibitor, Radiotherapy and GM-CSF) treatment and stereotactic radiotherapy (SBRT) combined with low-dose radiotherapy (LDRT) for advanced tumors. Therefore, the investigators designed a new radioimmunotherapy regimen, including SBRT, LDRT , PD-1/PD-L1 inhibitor, and GM-CSF. This study aimed to evaluate the safety and efficacy of the new regimen for advanced multiple metastatic solid tumors standard treatment failure/drug resistance, and explore the impact on immune function.

Study Timeline

• Study First Submitted: 2023-12-07
• Study First Submitted QC: 2023-12-07
• Study First Posted: 2023-12-15
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-25
• Last Update Posted: 2025-02-27
• Study Start: 2025-08-01
• Primary Completion: 2026-07-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

1. advanced malignant solid tumors with multiple metastases or relapses, with pathological diagnosis or medical record;
2. disease progression or recurrence after standard treatment, or unsuitable/intolerable for standard treatment, or rejection of standard treatment due to personal willingness;
3. patients with disease progression or drug resistance after previous immunotherapy are allowed to be included; a history of radiotherapy in the LDRT area or other sites is allowed to be included, provided that there are no residual toxic effects;
4. at least ≥1 lesion suitable for SBRT, and ≥1 lesion suitable for LDRT, and the above lesions must be measured;
5. no contraindications to radiotherapy;
6. Eastern Cooperative Oncology Group (ECOG) score: 0-2 points, and life expectancy >3 months;
7. important organ function is acceptable, defined as: white blood cells ≥3.0×10^9/L, platelets ≥75×10^9/L, hemoglobin ≥90g/L, glutamic pyruvic transaminase and glutamic oxalacetic transaminase ≤2.5 times the upper limit of normal value, serum creatinine < 178μmol/L;
8. voluntary participation and sign the informed consent.

Exclusion Criteria

1. no suitable lesions for radiotherapy, or the limit of important organs at risk could not be met;
2. permanent discontinuation of PD-1/L1 inhibitors due to ≥ grade 3 immune-related toxic reactions;
3. serious cardiovascular or cerebrovascular diseases, severe liver or kidney dysfunction, serious and uncontrolled systemic infections or other contraindications, or any contraindications to radiotherapy, and some comorbidities should be re-evaluated after symptomatic treatment;
4. any active immune system disease or related history;
5. systemic immunosuppressive drugs are expected to be used during the study;
6. a history of severe uncontrollable central nervous system diseases or mental disorders, which may hinder the signing of informed consent or treatment compliance;
7. other important medical or physiological conditions (such as pregnancy or breastfeeding status);
8. patients who are known to be allergic to the drugs used in this study;
9. patients refuse or are unable to sign the informed consent.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
treatment group	Radiotherapy combined with immunotherapy	The subjects will receive the combination therapy of SBRT, LDRT, PD-1/L1 inhibitor and GMCSF. The specific treatment regimen is as follows: (1) SBRT 8Gy×3f, (2) LDRT 2Gy ×3f, PD-1/L1 inhibitor, periodically, until the disease progresses or intolerable toxic side effects, (4) GM-CSF, 200ug/QD, subcutaneous injection, the first course of treatment for 7 days.

Primary Outcome Measures

Name	Time	Method
Adverse event rate	6 weeks	The proportion of treatment-related toxicities cases to the total evaluable cases, assessed according to CTCAE 5.0 criteria.

Secondary Outcome Measures

Name	Time	Method
Disease control rate	6weeks	Proportion of patients who achieved remission (PR+CR) or stable lesion (SD) after treatment.
Objective response rate	6 weeks	Proportion of patients whose tumor volume has shrunk to a predetermined value and can maintain the minimum time limit.

Trial Locations

Locations (1)

China-Japan Friendship Hospital; 🇨🇳 Beijing, Beijing, China