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

NCT07277777 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 960HP20251119
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Malignant Tumors

Keywords

lodine-125 Seed Brachytherapy; Immune Checkpoint Inhibitors; Local-Systemic Synergy; Recurrent or Refractory Tumors

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR)

  Proportion of patients achieving complete response (CR) or partial response (PR) as defined by RECIST 1.1 or iRECIST, assessed via CT/MRI/PET-CT.

  Every 6-12 weeks, up to 24 months

• Progression-Free Survival (PFS)

  Time from randomization to radiographic disease progression or death from any cause.

  Up to 24 months

Secondary Outcomes (9)

• Failure-Free Survival (FFS)

  Up to 24 months

• Overall Survival (OS)

  Up to 36 months

• Disease Control Rate (DCR)

  Every 6-12 weeks, up to 24 months

• Duration of Response (DoR)

  Up to 24 months

• Local Control Rate (LCR)

  Up to 24 months

Other Outcomes (3)

• Radiomics Features and Predictive Modeling

  Up to 24 months

• Subgroup Analyses

  Up to 24 months

• Patterns of Failure / Recurrence Patterns

  Up to 24 months

Study Arms (2)

125I Seed Brachytherapy + Immunotherapy

EXPERIMENTAL

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.

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

Immunotherapy Alone

ACTIVE COMPARATOR

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.

Drug: Immune Checkpoint Inhibitors

Interventions

125I Seed Implantation OTHER

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

125I Seed Brachytherapy + Immunotherapy

Immune Checkpoint Inhibitors DRUG

Examples include PD-1/PD-L1 inhibitors (e.g., pembrolizumab, nivolumab, camrelizumab, sintilimab) Administered per standard dosing schedule (e.g., every 2-3 weeks)

125I Seed Brachytherapy + Immunotherapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Li Min: lead

Study Sites (1)

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

Jinan, Shandong, 250031, China

Location

MeSH Terms

Conditions

Neoplasms; Recurrence

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Min Li, Dr.

  STUDY DIRECTOR

Central Study Contacts

Min Li, Dr.

CONTACT

0531-51665482; liminyingxiang.@163.com

Min Li, Dr.

CONTACT

924787237@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Due to the procedural nature of 125I seed implantation, blinding of participants and treating clinicians is not feasible. However, imaging evaluators-including independent radiologists and nuclear medicine physicians responsible for tumor response assessment and imaging-based efficacy evaluations-will remain blinded to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Vice Director

Model Details: This is a two-arm, parallel-group, phase II trial in which eligible patients with recurrent or refractory, unresectable malignant tumors are randomized in a 1:1 ratio to receive either 125I seed interstitial brachytherapy combined with immune checkpoint inhibitor therapy or immune checkpoint inhibitor therapy alone. Treatment allocation remains fixed throughout the study; no crossover between arms is planned. Patients will be treated and followed according to the assigned arm until disease progression, unacceptable toxicity, withdrawal of consent, or study completion.

Study Record Dates

• First Submitted: November 30, 2025
• First Posted: December 11, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: January 6, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Individual participant data (IPD) will be available beginning 6 months after publication of the primary study results and will remain available for 5 years following publication, or until the main study database is closed, whichever occurs first.
• Access Criteria: Qualified researchers affiliated with academic institutions or recognized research organizations may request access to de-identified individual participant data (IPD), including imaging-derived parameters, dosimetric results, and clinical outcome data. Requests must include a brief research proposal describing the scientific rationale, objectives, and planned analyses. Approval will be granted by the study's principal investigator and institutional ethics committee. Data will be shared through secure institutional data transfer systems after execution of a formal data sharing agreement that ensures patient confidentiality and compliance with applicable privacy regulations.

Locations

CN (1)