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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Prospective Clinical Trial Evaluating the Safety and Efficacy of Radiotherapy Combined With Immunotherapy in Advanced Refractory Solid Malignancies After Standard Treatment Failure/Drug Resistance.

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Combination Product: Radiotherapy combined with immunotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: advanced malignant solid tumors with multiple metastases or relapses, with pathological diagnosis or medical record; disease progression or recurrence after standard treatment, or unsuitable/intolerable for standard treatment, or rejection of standard treatment due to personal willingness; 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; at least ≥1 lesion suitable for SBRT, and ≥1 lesion suitable for LDRT, and the above lesions must be measured; no contraindications to radiotherapy; Eastern Cooperative Oncology Group (ECOG) score: 0-2 points, and life expectancy >3 months; 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; voluntary participation and sign the informed consent. Exclusion Criteria: no suitable lesions for radiotherapy, or the limit of important organs at risk could not be met; permanent discontinuation of PD-1/L1 inhibitors due to ≥ grade 3 immune-related toxic reactions; 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; any active immune system disease or related history; systemic immunosuppressive drugs are expected to be used during the study; a history of severe uncontrollable central nervous system diseases or mental disorders, which may hinder the signing of informed consent or treatment compliance; other important medical or physiological conditions (such as pregnancy or breastfeeding status); patients who are known to be allergic to the drugs used in this study; patients refuse or are unable to sign the informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment group<br>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. | Combination Product: Radiotherapy combined with immunotherapy<br>* (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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event rate | The proportion of treatment-related toxicities cases to the total evaluable cases, assessed according to CTCAE 5.0 criteria. | 6 weeks | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced solid tumor, standard treatment failure, radiotherapy, immunotherapy