"This prospective, single-institution Phase I/II clinical trial investigates the safety, feasibility, and preliminary efficacy of preoperative carbon-ion radiotherapy (CIRT) for patients with resectable soft tissue sarcoma. Given the radioresistant nature of sarcomas and the limitations of photon-based preoperative radiotherapy-particularly high wound complication rates-CIRT is expected to enhance local tumor control while minimizing treatment-related toxicity and surgical morbidity. The trial consists of an initial dose-escalation phase (phase 1) to identify an optimal and tolerable dose level, followed by an expansion phase (phase 2) assessing the feasibility of completing both CIRT and surgery without major wound complications. CIRT is delivered in eight fractions over two weeks, with surgery planned 6-8 weeks after radiotherapy. Primary endpoints include the incidence of grade 3-5 post-operative wound complications within 120 days and overall treatment completion. Secondary endpoints include pathological response, surgical outcomes, local control, progression-free survival, overall survival, and patient-reported quality of life. All participants will be followed for at least 12 months postoperatively to evaluate safety and long-term outcomes.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Participants receive preoperative CIRT as the investigational intervention, delivered in 8 fractions, once daily, four times per week. In Phase I, three dose levels (DL1: 32.0 GyE, DL2: 34.0 GyE, DL3: 36.0 GyE) are evaluated using a 3+3 dose-escalation design to determine the recommended Phase II dose (RP2D). Three patients are initially enrolled per dose level, expanded to six if dose-limiting toxicities occur. In Phase II, all participants receive CIRT at the RP2D following a Simon's two-stage design (Stage I: 20 patients; Stage II: 22 additional if criteria met). Treatment uses fixed-beam or rotating gantry techniques. Post-treatment imaging (CT or MRI) is performed 4-6 weeks after CIRT, followed by surgical resection 6-8 weeks post-radiotherapy. All participants are followed for at least 12 months after surgery to assess postoperative wound complications, treatment completion, and overall outcomes.
Yonsei Cancer Center, Yonsei University College of Medicine, Yonsei University Health System
Seoul, South Korea
Phase I: Incidence of Dose-Limiting Toxicities (DLTs)
To evaluate the safety and tolerability of preoperative CIRT and identify the optimal tolerated dose level. DLTs are defined as grade ≥3 toxicities, including severe wound complications, prolonged hospitalization, or significant treatment delay, assessed according to CTCAE version 5.0.
Time frame: From initiation of CIRT to 30 days after surgery
Phase II: Proportion of Patients Completing Both CIRT and Surgery Without Grade 3-5 Postoperative Wound Complications or Serious Adverse Events
To determine the clinical feasibility and safety of completing preoperative CIRT followed by surgical resection without major wound-healing complications or treatment-related serious adverse events (SAEs). The endpoint represents the proportion of patients achieving treatment completion without grade 3-5 wound complications or other SAEs within 120 days postoperatively.
Time frame: From initiation of CIRT to 120 days after surgery
Incidence of Acute Treatment-Related Toxicities
To record and grade all acute adverse events associated with preoperative carbon-ion radiotherapy using CTCAE v5.0 criteria to characterize the overall safety profile at each dose level.
Time frame: From initiation of CIRT to 30 days after surgery
Surgery Feasibility and Completion Rate
To assess the proportion of participants who successfully undergo and complete surgical resection following preoperative CIRT without protocol deviation or treatment interruption.
Time frame: From completion of CIRT to 30 days after surgery
Pathological Tumor Response Rate
To determine the rate of pathological tumor regression or necrosis in resected specimens following preoperative CIRT, based on standardized histologic grading criteria.
Time frame: At surgical specimen evaluation (6-8 weeks after CIRT)
R0 Resection Rate
To evaluate the proportion of patients achieving microscopically margin-negative (R0) resection after preoperative CIRT, reflecting its impact on surgical resectability.
Time frame: At surgery (6-8 weeks after CIRT)
Local Control and Progression-Free Survival
To estimate 1-year local control and progression-free survival using Kaplan-Meier analysis as measures of preliminary efficacy.
Time frame: From date of surgery to 12 months postoperatively
Overall Survival
To evaluate 12-month overall survival as an exploratory efficacy endpoint of preoperative CIRT.
Time frame: From initiation of CIRT to 12 months postoperatively
Quality of Life (EORTC QLQ-C30)
To assess longitudinal changes in patient-reported quality of life using the EORTC QLQ-C30 questionnaire throughout treatment and follow-up.
Time frame: Baseline, post-CIRT, and 3, 6, and 12 months after surgery
Body Composition Change (InBody Analysis) : Skeletal-Muscle Mass Change
Unit of Measure: kg
Time frame: Baseline, post-CIRT, and 3, 6, and 12 months after surgery
Body Composition Change (InBody Analysis) :Body-Fat Composition Change
Body-Fat Composition Change
Time frame: Baseline, post-CIRT, and 3, 6, and 12 months after surgery
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