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

Официальное название

A Prospective, Randomized, Open-Label, Parallel-Group Clinical Trial Evaluating the Efficacy and Safety of 125I Seed Interstitial Brachytherapy Combined With Immune Checkpoint Inhibitor Therapy in Patients With Primary, Recurrent, or Metastatic Malignant Tumors Compared With Immune Checkpoint Inhibitor Therapy Alone

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Immune Checkpoint Inhibitors
  Examples include PD-1/PD-L1 inhibitors (e.g., pembrolizumab, nivolumab, camrelizumab, sintilimab) Administered per standard dosing schedule (e.g., every 2-3 weeks)
• Другое 125I Seed Implantation
  PET/CT-guided implantation or CT-guided implantation Dose planning: D90 typically 90-140 Gy (adjusted per tumor type and size) Post-implant dosimetry: D90, V100, V150 recorded
• Препарат Immune Checkpoint Inhibitors
  Same agent class and dosing schedule as the experimental arm Administered until disease progression, unacceptable toxicity, or study completion

Первичные конечные точки

• Objective Response Rate (ORR) [Срок оценки: Every 6-12 weeks, up to 24 months]
• Progression-Free Survival (PFS) [Срок оценки: Up to 24 months]

Вторичные конечные точки (9)

• Failure-Free Survival (FFS) [Срок оценки: Up to 24 months]
• Overall Survival (OS) [Срок оценки: Up to 36 months]
• Disease Control Rate (DCR) [Срок оценки: Every 6-12 weeks, up to 24 months]
• Duration of Response (DoR) [Срок оценки: Up to 24 months]
• Local Control Rate (LCR) [Срок оценки: Up to 24 months]
• Tumor Recurrence Rate [Срок оценки: Up to 24 months]
• Treatment-Related Adverse Events (TRAEs) [Срок оценки: From baseline until 90 days after last treatment]
• Immune-Related Adverse Events (irAEs) [Срок оценки: Up to 24 months]
• Quality of Life (QoL) [Срок оценки: Baseline, Week 12, Week 24, and every 6 months up to 24 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The 960th Hospital of People's Liberation Army (PLA) — Цзинань

Идентификаторы

NCT: NCT07277777 · 960HP20251119

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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