125I Seed Brachytherapy Combined With Immunotherapy for Primary, Recurrent, or Metastatic Malignant Tumors

Li Min

Status and phase: Not yet enrolling; Phase 2

Conditions: Malignant Tumors

Treatments: Drug: Immune Checkpoint Inhibitors; Other: 125I Seed Implantation

Study type: Interventional

Funder types: Other

Identifiers

NCT07277777

960HP20251119

Details and patient eligibility

About

This prospective randomized trial evaluates the efficacy and safety of combining 125I seed interstitial brachytherapy with immune checkpoint inhibitor therapy in patients with primary, recurrent, or metastatic malignant tumors. Immunotherapy has become an important systemic treatment option, yet many patients experience limited benefit due to low tumor immunogenicity, insufficient T-cell infiltration, and an immunosuppressive tumor microenvironment.

125I seed brachytherapy provides continuous low-dose-rate radiation to the tumor, promoting antigen release, enhancing dendritic cell activation, and potentially converting immunologically "cold" tumors into more responsive "hot" lesions. Integrating localized radiation with systemic immunotherapy may improve tumor response, prolong progression-free survival, and reduce recurrence.

Patients will be randomized 1:1 to receive 125I seed implantation plus immunotherapy or immunotherapy alone. The primary endpoints are objective response rate (ORR) and progression-free survival (PFS). Secondary endpoints include failure-free survival (FFS), overall survival (OS), disease control rate (DCR), duration of response (DoR), local control, recurrence rate, adverse events, and quality of life. Exploratory analyses will assess radiomics features, subgroup responses, and different patterns of recurrence. This study aims to determine whether adding 125I seed brachytherapy enhances the clinical benefits of immunotherapy across diverse malignant tumors.

Full description

Patients with malignant tumors-including primary, recurrent, and metastatic disease-often exhibit heterogeneous responses to immune checkpoint inhibitors (ICIs). Limited tumor antigen exposure, poor immune infiltration, and an immunosuppressive tumor microenvironment frequently restrict the efficacy of immunotherapy. Strategies capable of enhancing local tumor immunogenicity and promoting systemic immune activation may improve clinical outcomes.

125I seed interstitial brachytherapy delivers continuous low-dose-rate radiation precisely to the tumor, offering both durable local control and immunomodulatory effects. Low-dose-rate irradiation can induce immunogenic tumor cell death, increase tumor antigen presentation, enhance dendritic cell activation, and promote T-cell recruitment. This process may convert immunologically inactive ("cold") tumors into immunologically active ("hot") lesions, thereby synergizing with ICIs to enhance anti-tumor immunity. Combining these modalities may improve objective response, delay treatment failure, reduce recurrence, and prolong survival.

This prospective, randomized, open-label, parallel-group trial will compare 125I seed brachytherapy plus immunotherapy with immunotherapy alone. Eligible patients will be randomized 1:1. The combination arm will receive CT-guided seed implantation followed by ICI therapy; the control arm will receive ICI monotherapy. All patients will undergo standardized imaging and clinical evaluations at pre-defined intervals.

The primary endpoints are objective response rate (ORR) and progression-free survival (PFS). Secondary endpoints include failure-free survival (FFS), overall survival, disease control rate, duration of response, local control rate, tumor recurrence rate, treatment-related and immune-related adverse events, and patient-reported quality of life. Exploratory analyses will investigate radiomics features associated with response, patterns of recurrence (local, regional, or distant), and subgroup differences across tumor types, disease stages, biomarker profiles, and treatment characteristics. These analyses may help identify imaging or clinical predictors of benefit, refine patient selection, and support biomarker-driven optimization of 125I seed brachytherapy combined with immunotherapy.

Enrollment: 90 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age 18 to 80 years.
• Histologically or clinically confirmed primary, recurrent, or metastatic malignant tumor.
• At least one measurable lesion according to RECIST 1.1 or iRECIST.
• Tumor site suitable for 125I seed implantation under CT or PET/CT guidance.
• Planned to receive or eligible to receive an immune checkpoint inhibitor (ICI).
• ECOG performance status 0-2.
• Adequate organ function:

ANC ≥ 1.5 × 10⁹/L Platelets ≥ 80 × 10⁹/L Hemoglobin ≥ 90 g/L AST/ALT ≤ 3 × ULN (≤ 5 × ULN for liver metastasis) Creatinine clearance ≥ 50 mL/min

• Life expectancy ≥ 3 months.
• Ability to understand and sign informed consent.

Exclusion criteria

• Prior I-125 seed implantation at the planned treatment site.
• Active uncontrolled infection or systemic inflammatory disease.
• Known history of autoimmune disease requiring systemic immunosuppression.
• Prior treatment with immune checkpoint inhibitors within the last 4 weeks.
• Uncontrolled coagulopathy or contraindication to interventional seed implantation:

INR > 1.5 Platelets < 50 × 10⁹/L

• Tumor location that poses unacceptable procedural risk, including inability to obtain a safe puncture path.
• Severe cardiopulmonary dysfunction (e.g., heart failure, unstable arrhythmia, severe COPD).
• Pregnancy or breastfeeding.
• Known allergy or contraindication to radiopharmaceuticals, contrast agents, or anesthesia agents used during implantation.
• Any condition that, in the investigator's judgment, makes the participant unsuitable for the study (e.g., poor compliance, severe psychiatric disorder).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 2 patient groups

125I Seed Brachytherapy + Immunotherapy

Experimental group

Description:

Participants in this arm will receive CT-guided 125I seed interstitial brachytherapy, followed by systemic immune checkpoint inhibitor (ICI) therapy administered according to the approved dosing schedule for the selected agent. Seed implantation will be planned and delivered using standardized TPS-based dosimetric protocols, and immunotherapy will continue until progression, unacceptable toxicity, or study completion.

Treatment:

Other: 125I Seed Implantation

Drug: Immune Checkpoint Inhibitors

Drug: Immune Checkpoint Inhibitors

Immunotherapy Alone

Active Comparator group

Description:

Participants in this arm will receive systemic immune checkpoint inhibitor (ICI) therapy alone, following the same agent, schedule, and supportive care standards used in the experimental arm. No local radiotherapy or seed implantation will be performed. Treatment will continue until disease progression, unacceptable toxicity, or study completion.

Treatment:

Drug: Immune Checkpoint Inhibitors

Drug: Immune Checkpoint Inhibitors