Image-Guided 125I Seed Implantation Plus Standard Systemic Therapy for Patients With Multiple Metastatic Lesions

Standard-of-Care Systemic Therapy With or Without Image-Guided 125I Seed Implantation in Patients With Multiple (6-10) Metastatic Lesions: A Randomized Phase 2 Study

Patients with more than five and up to ten metastatic lesions often have limited tolerance for surgery, radiotherapy, or thermal ablation because of cumulative treatment burden or expected toxicity. In this setting, systemic therapy alone frequently remains the primary treatment option.

This prospective, open-label, randomized phase 2 study evaluates whether image-guided iodine-125 (125I) seed implantation, when added to standard-of-care systemic therapy, can improve disease control compared with standard systemic therapy alone in patients with multiple metastatic lesions. Clinical outcomes including progression-free survival, overall survival, safety, and quality of life will be prospectively assessed.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Solid Tumors
• Intervention / Treatment: Other: Standard-of-Care Systemic Therapy; Procedure: Iodine-125 (125I) Seed Implantation

Detailed Description

This is a prospective, open-label, randomized phase 2 interventional study designed to evaluate the efficacy and safety of image-guided iodine-125 (125I) seed implantation in combination with standard-of-care systemic therapy compared with standard systemic therapy alone in patients with multiple metastatic lesions. Patients with more than five and up to ten extracranial metastatic lesions often have limited tolerance for surgery, radiotherapy, or thermal ablation due to cumulative treatment burden or expected toxicity, and in this setting, systemic therapy alone frequently remains the only treatment option. This study therefore explores the potential role of image-guided radioactive seed implantation as an additional local treatment strategy for this patient population.

After eligibility confirmation and baseline assessments, participants will be randomly assigned in a 1:1 ratio to receive either standard-of-care systemic therapy alone or image-guided 125I seed implantation plus standard-of-care systemic therapy. Randomization will be performed using a predefined allocation scheme, and the study is conducted in an open-label manner due to the interventional nature of the procedure.

The primary endpoint of the study is progression-free survival (PFS), defined as the time from randomization to disease progression or death from any cause, whichever occurs first. Secondary endpoints, aligned with prior randomized studies of metastasis-directed therapy, include overall survival, time to initiation of a new systemic therapy, treatment-related adverse events, and patient-reported quality of life. Exploratory objectives include descriptive analyses of patterns of disease progression.

Participants assigned to the experimental arm will undergo image-guided 125I seed implantation targeting multiple metastatic lesions, performed under CT guidance (with PET/CT fusion planning when clinically indicated) according to institutional standards. Systemic anticancer therapy will be administered in both study arms at the discretion of the treating physician in accordance with current clinical guidelines. All participants will undergo scheduled clinical and imaging follow-up, with disease progression assessed using RECIST version 1.1 and/or PERCIST criteria.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Min Li, M.D.; Phone Number: 0531-51665482; Email: liminyingxiang.@163.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250031
      • The 960th Hospital of People's Liberation Army (PLA)
      • Contact: Min Li, M.D.; Phone Number: 0531-51665482; Email: liminyingxiang@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Histologically or cytologically confirmed malignant solid tumor with metastatic disease.
• Presence of more than five and up to ten (6-10) extracranial metastatic lesions, identified on CT or PET/CT imaging and assessable by RECIST version 1.1 (and/or PERCIST when PET imaging is used).
• At least one metastatic lesion considered suitable for image-guided iodine-125 (125I) seed implantation according to institutional assessment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Adequate organ function to undergo interventional procedures and systemic therapy, as determined by institutional standards.
• Ability to understand and willingness to provide written informed consent.

Exclusion Criteria:

• Diffuse or unstable central nervous system involvement, including leptomeningeal disease or uncontrolled/symptomatic brain metastases requiring immediate local intervention.
• Medical conditions that preclude safe interventional procedures, including uncontrolled infection, severe cardiopulmonary dysfunction, or other serious systemic illness, as judged by the investigator.
• Contraindications to percutaneous implantation, such as uncorrectable coagulation disorders, high bleeding risk, lack of a safe needle path, or unacceptable risk to critical organs.
• Pregnancy or breastfeeding.
• Inability to provide informed consent or comply with study procedures, due to severe psychiatric illness, cognitive impairment, or other limiting conditions.
• Any other condition that, in the investigator's judgment, would make the patient unsuitable for study participation or compromise patient safety or study integrity.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard-of-Care Systemic Therapy; Participants receive standard-of-care systemic anticancer therapy according to current clinical guidelines and treating physician discretion.	Other: Standard-of-Care Systemic Therapy; Systemic anticancer therapy administered according to current clinical guidelines and treating physician discretion, which may include chemotherapy, immunotherapy, targeted therapy, and/or maintenance therapy.
Experimental: 125I Seed Implantation plus Standard-of-Care Systemic Therapy; Participants receive image-guided iodine-125 (125I) seed implantation to multiple metastatic lesions in combination with standard-of-care systemic anticancer therapy.	Other: Standard-of-Care Systemic Therapy; Systemic anticancer therapy administered according to current clinical guidelines and treating physician discretion, which may include chemotherapy, immunotherapy, targeted therapy, and/or maintenance therapy.; Procedure: Iodine-125 (125I) Seed Implantation; Image-guided implantation of iodine-125 (125I) radioactive seeds to multiple metastatic lesions for local tumor control, performed under CT guidance (with PET/CT fusion planning when clinically indicated) according to institutional standards.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	Progression-free survival is defined as the time from randomization to disease progression or death from any cause, whichever occurs first. Disease progression will be assessed using RECIST version 1.1 and/or PERCIST criteria, based on the baseline imaging modality.	From randomization up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life (QoL)	Quality of life is assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Scores range from 0 to 100. Higher scores on functioning scales and global health status indicate better outcomes, while higher scores on symptom scales indicate worse symptoms.	Baseline, and 6 months
Overall Survival (OS)	Overall survival is defined as the time from randomization to death from any cause.	From randomization up to 24 months
Time to Initiation of a New Systemic Therapy (TTNT)	Time to initiation of a new systemic therapy is defined as the time from randomization to the start of a new line or regimen of systemic anticancer therapy due to disease progression or clinical decision.	From randomization up to 12 months
Local Control of Treated Lesions	Local control is defined as the absence of in-field progression of metastatic lesions treated with iodine-125 (125I) seed implantation on follow-up imaging.	From intervention up to 12 months
Safety and Treatment-Related Adverse Events	Incidence and severity of adverse events, including procedure-related toxicities, graded according to the Common Terminology Criteria for Adverse Events (CTCAE).	From intervention through 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patterns of Disease Progression	Patterns of disease progression will be descriptively analyzed, including the development of new metastatic lesions versus progression of pre-existing lesions, based on radiographic and/or clinical assessment at the time of disease progression.	From the date of randomization until the date of first documented disease progression, assessed up to 24 months.

Collaborators and Investigators

• Sponsor: Li Min

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: December 19, 2025
• First Submitted That Met QC Criteria: January 2, 2026
• First Posted (Estimated): January 12, 2026

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: January 2, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: lodine-125 Seed Brachytherapy; Multiple Metastases; Image-Guided Therapy
• Additional Relevant MeSH Terms: Iodine-125
• Other Study ID Numbers: 960HP20251220

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) will be made available to qualified researchers upon reasonable request after completion of the study and publication of the primary results. Data to be shared may include demographic information, treatment assignment, key efficacy outcomes, adverse events, and imaging-derived parameters. A data-sharing agreement will be required to ensure appropriate use of the dataset.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No