Prospective Phase I/II Study Evaluating the Safety and Efficacy of Preoperative Carbon Ion Radiotherapy in Patients With Soft Tissue Sarcoma : The SARCOMA-01 Trial by the Severance sARCOma Multidisciplinary Team (SARCOMA-01)

"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 Overview

• Status: Not yet recruiting
• Conditions: Soft Tissue Sarcoma
• Intervention / Treatment: Radiation: Carbon-Ion Radiotherapy (CIRT)

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• South Korea
  • Seoul, South Korea
    • Yonsei Cancer Center, Yonsei University College of Medicine, Yonsei University Health System

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adults aged 19 years or older.
• Histologically confirmed soft tissue sarcoma deemed suitable for curative resection.
• Determined by the Yonsei Cancer Center sarcoma multidisciplinary team that preoperative carbon-ion radiotherapy followed by surgery is appropriate, considering tumor histologic subtype, size, and location.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 or Karnofsky Performance Status (KPS) ≥ 70.
• Adequate organ function (including hematologic, hepatic, and renal function) suitable for radiotherapy and surgery.
• Voluntarily provided written informed consent.

Exclusion Criteria:

• Presence of distant metastases.
• Inability to plan carbon-ion radiotherapy due to metallic implants or other factors at the tumor site.
• History of prior radiotherapy to the same anatomical region.
• Presence of other serious medical conditions or active infections that, in the investigator's judgment, could interfere with study participation.
• Presence of active implanted electronic devices (e.g., pacemaker or defibrillator) without established safety for carbon-ion radiotherapy.
• Pregnant or breastfeeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CIRT Group; Phase I (Dose-Escalation) Participants in the Phase I cohort will receive preoperative CIRT using a dose-escalation design to identify an optimal tolerated dose. Three dose levels are evaluated-32.0, 34.0, and 36.0 GyE/8 fractions-delivered in 2 weeks (4 fr/week). Surgical resection is performed 6-8 weeks after CIRT, followed by postoperative evaluation of wound healing, toxicity, and surgical outcomes. Phase II (Feasibility and Safety Evaluation) All enrolled patients will receive preoperative CIRT at the optimal dose determined in Phase I. The regimen consists of 8 fractions (4 fr/week), followed by surgical resection 6-8 weeks later. Postoperative assessments focus on feasibility and safety, particularly grade 3-5 wound complications within 120 days after surgery. Secondary analyses include pathological response, R0 resection rate, local control, survival, and quality of life. Participants are followed for at least 12 months to assess long-term safety and efficacy.

Radiation: Carbon-Ion Radiotherapy (CIRT); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	From initiation of CIRT to 120 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	From date of surgery to 12 months postoperatively
Overall Survival	To evaluate 12-month overall survival as an exploratory efficacy endpoint of preoperative CIRT.	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.	Baseline, post-CIRT, and 3, 6, and 12 months after surgery
Body Composition Change (InBody Analysis) : Skeletal-Muscle Mass Change	Unit of Measure: kg	Baseline, post-CIRT, and 3, 6, and 12 months after surgery
Body Composition Change (InBody Analysis) :Body-Fat Composition Change	Body-Fat Composition Change	Baseline, post-CIRT, and 3, 6, and 12 months after surgery

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2025
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 24, 2025
• First Posted (Actual): November 26, 2025

Study Record Updates

• Last Update Posted (Actual): November 26, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Sarcoma; Therapeutics; Radiotherapy; Heavy Ion Radiotherapy
• Other Study ID Numbers: 4-2025-1025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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