Lesion-Allocated Therapy for Multiple Metastases and Tumor-Zoned Treatment for Bulky Tumors: A Phase II Study of Iodine-125 Seed Implantation Combined With Cryoablation in High-Burden Metastatic Disease

NCT07437625 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 960HP20260222
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This open-label, randomized Phase II trial evaluates whether a strategy-based, multimodal local treatment approach improves local control compared with single-modality local therapy in patients with high-burden metastatic disease characterized by multiple metastases and at least one bulky lesion. In the experimental arm, prespecified target lesions are prospectively allocated to either iodine-125 (125I) seed implantation or cryoablation using protocol-defined anatomic and technical suitability criteria, and at least one bulky index lesion is treated using a tumor-zoned approach (e.g., core debulking with cryoablation and peripheral/high-risk margin control with 125I seeds) under predefined organ-at-risk constraints. The control arm treats all prespecified target lesions with a single local modality (either 125I seed implantation alone or cryoablation alone), with standardized supportive care and follow-up. The primary objective is to determine whether the "lesion allocation plus tumor zoning" strategy can improve local control of treated target lesions with acceptable safety. Imaging-based efficacy endpoints are evaluated using protocol-defined criteria with standardized blinded independent imaging review. Key secondary endpoints include local progression-free survival of the bulky index lesion, overall response rate (RECIST), progression-free survival, time to systemic progression (including new lesions), overall survival, tumor-burden reduction metrics, technical success, and re-intervention rates. Safety is assessed throughout the study using CTCAE v5.0, including monitoring for procedure-related and radiation-related complications. Exploratory analyses assess dosimetry-outcome relationships, zonal response patterns within bulky lesions, imaging/radiomics biomarkers, and peripheral blood biomarker dynamics.

Conditions

High-Burden Metastatic Solid Tumors

Keywords

Iodine-125 seed implantation; Cryoablation; High tumor burden; Multiple metastases; Lesion allocation; Tumor zoning; Local control

Outcome Measures

Primary Outcomes (2)

• Local Control Rate (LCR) of Treated Target Lesions

  Proportion of prespecified treated target lesions without local progression by blinded independent imaging review per protocol-defined criteria.

  6 months after completion of protocol local therapy

• Local Progression-Free Survival (LPFS) of the Bulky Index Lesion

  Time from randomization to local progression of the prespecified bulky index lesion or death from any cause, whichever occurs first, assessed by blinded independent imaging review.

  Up to 12 months

Secondary Outcomes (7)

• Progression-Free Survival (PFS)

  Up to 12 months

• Overall Response Rate (ORR)

  First assessment at ~8-12 weeks; up to 6 months

• Time to Systemic Progression

  Up to 12 months

• Overall Survival (OS)

  Up to 24 months

• Tumor-Burden Reduction

  Baseline to 3 months and 6 months

Other Outcomes (3)

• Zonal Response of Bulky Index Lesion

  Baseline to 8-12 weeks and 6 months

• Peripheral Blood Biomarker Dynamics

  Baseline; post-procedure/early follow-up (~2-4 weeks); then through 6-12 months

• Patterns of Failure

  Up to 12 months

Study Arms (2)

Lesion-Allocated + Tumor-Zoned Combined Local Therapy (125I Seeds + Cryoablation)

EXPERIMENTAL

Participants receive strategy-based multimodal local therapy. Prespecified metastatic target lesions are prospectively allocated to either iodine-125 (125I) seed implantation or cryoablation according to protocol-defined anatomic and technical suitability criteria. In addition, at least one bulky index lesion is treated using a tumor-zoned approach (e.g., core debulking with cryoablation and peripheral/high-risk margin control with \^125I seeds) under predefined organ-at-risk constraints. Standardized follow-up and supportive care are provided per protocol.

Other: Lesion Allocation and Tumor Zoning Strategy

Single-Modality Local Therapy (Cryoablation Alone or ^125I Seeds Alone)

ACTIVE COMPARATOR

Participants receive single-modality local therapy for all prespecified target lesions, using either cryoablation alone or iodine-125 (125I) seed implantation alone as specified by the protocol and/or center capability, with standardized supportive care and follow-up. Imaging-based efficacy endpoints are assessed per protocol with standardized blinded independent review.

Procedure: Iodine-125 (125I) Seed Implantation (Low-Dose-Rate Brachytherapy); Procedure: cryoablation

Interventions

Iodine-125 (125I) Seed Implantation (Low-Dose-Rate Brachytherapy) PROCEDURE

Image-guided percutaneous implantation of 125I radioactive seeds into prespecified target lesions according to protocol-defined treatment planning and organ-at-risk constraints. Seed number and distribution are determined by pre-implant planning to achieve protocol-specified target coverage, with post-implant verification imaging and dosimetry as required.

Single-Modality Local Therapy (Cryoablation Alone or ^125I Seeds Alone)

cryoablation PROCEDURE

Image-guided percutaneous cryoablation of prespecified target lesions using standardized probe placement and freeze-thaw cycles per protocol. The ablation zone is planned to achieve protocol-defined tumor coverage while maintaining safety margins to adjacent critical structures, with intraprocedural monitoring and post-procedure imaging assessment.

Single-Modality Local Therapy (Cryoablation Alone or ^125I Seeds Alone)

Lesion Allocation and Tumor Zoning Strategy OTHER

Protocol-defined decision rules assign each prespecified metastatic target lesion to 125I seed implantation or cryoablation based on anatomic and technical suitability criteria. For at least one bulky index lesion, a tumor-zoned approach is applied (e.g., core debulking with cryoablation and peripheral/high-risk margin control with 125I seeds) under predefined organ-at-risk constraints and quality assurance requirements.

Lesion-Allocated + Tumor-Zoned Combined Local Therapy (125I Seeds + Cryoablation)

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years;
• Histologically or cytologically confirmed solid malignancy with metastatic disease not amenable to curative surgery or definitive curative-intent radiotherapy;
• High-burden metastatic disease, defined as: Multiple metastases: ≥3 metastatic lesions on imaging, and at least 2 measurable lesions (RECIST v1.1) planned as protocol target lesions; and Bulky lesion: at least 1 lesion meeting bulky criteria (e.g., longest diameter ≥7 cm or tumor volume ≥100 mL, per protocol) designated as the bulky index lesion;
• At least 2 and up to 5 prespecified target lesions are suitable for protocol local therapy and can be assigned per protocol (lesion allocation and/or tumor zoning);
• ECOG performance status 0-2;
• Adequate organ function;
• Willing and able to provide written informed consent.

You may not qualify if:

• Lesions requiring emergent surgical decompression or other urgent intervention that cannot be deferred to protocol timelines;
• Target lesions not safely accessible for percutaneous cryoablation and/or 125I seed implantation (e.g., no feasible needle path, unacceptable risk to critical structures despite protective maneuvers);
• Active, uncontrolled infection; uncontrolled pleural effusion/ascites requiring frequent drainage (unless stabilized);
• Severe cardiopulmonary comorbidity prohibiting anesthesia/sedation or percutaneous intervention (e.g., unstable angina, recent MI, uncontrolled arrhythmia, severe COPD with high oxygen requirement);
• Prior local therapy to the same bulky index lesion that would confound response assessment (prior treatment to other non-index lesions may be allowed);
• Uncontrolled CNS metastases (symptomatic, requiring escalating steroids, or not stable after local therapy). Stable treated brain metastases may be allowed per protocol;
• Any condition that, in the investigator's judgment, would compromise protocol compliance or make participation unsafe.

Sponsors & Collaborators

• Li Min: lead

Study Sites (1)

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

Jinan, Shandong, 250031, China

Location

MeSH Terms

Interventions

Iodine-125; Cryosurgery

Intervention Hierarchy (Ancestors)

Ablation Techniques; Surgical Procedures, Operative

Study Officials

• Min Li

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

  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 and cryoablation, blinding of participants and treating clinicians is not feasible; therefore, the study is open label. 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, with adjudication when necessary to minimize assessment bias.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Vice Director

Model Details: This strategy-based local therapy model uses (1) lesion allocation of prespecified metastatic targets to either 125I seed implantation or cryoablation using predefined suitability criteria, and (2) tumor-zoned treatment of a bulky index lesion (core debulking plus peripheral/high-risk margin control) under organ-at-risk constraints, compared with single-modality local therapy for all target lesions.

Study Record Dates

• First Submitted: February 22, 2026
• First Posted: February 27, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: February 27, 2026

Record last verified: 2026-02

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.

Locations

CN (1)