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

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Combination product: Radiotherapy combined with 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 Type: Interventional
• Enrollment (Estimated): 38
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Guangying Zhu, M.D.; Phone Number: +86-010 84205381; Email: zryyfa@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Recruiting
      • China-Japan Friendship Hospital
      • Contact: Guangying Zhu, M.D.; Phone Number: +86 01084205381; Email: zryyfa@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: treatment group; 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; (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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: China-Japan Friendship Hospital
• Investigators: Principal Investigator: Guangying Zhu, M.D., China-Japan Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2025
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 7, 2023
• First Submitted That Met QC Criteria: December 7, 2023
• First Posted (Actual): December 15, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 25, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: immunotherapy; radiotherapy; advanced solid tumor; standard treatment failure
• Additional Relevant MeSH Terms: Immunologic Factors; Physiological Effects of Drugs; Immunomodulating Agents
• Other Study ID Numbers: 2023-ZF-63

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Original research data including study protocol and statistical analysis plan will be shared after the study is completed and the research results are published.
• IPD Sharing Time Frame: The data will become available starting 6 months and ending 5 years following article publication.
• IPD Sharing Access Criteria: People who provide reasonable research protocols can get access to the data by contacting the researchers.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No