Clinical Research Directory

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

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.