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

NCT07250334 | Not Yet Recruiting

• 1 other identifier: 4-2025-1025
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

"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.

Conditions

Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Incidence of Acute Treatment-Related Toxicities

  From initiation of CIRT to 30 days after surgery

• Surgery Feasibility and Completion Rate

  From completion of CIRT to 30 days after surgery

• Pathological Tumor Response Rate

  At surgical specimen evaluation (6-8 weeks after CIRT)

• R0 Resection Rate

  At surgery (6-8 weeks after CIRT)

• Local Control and Progression-Free Survival

  From date of surgery to 12 months postoperatively

Study Arms (1)

CIRT Group

EXPERIMENTAL

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)

Interventions

Carbon-Ion Radiotherapy (CIRT) RADIATION

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.

CIRT Group

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Yonsei Cancer Center, Yonsei University College of Medicine, Yonsei University Health System

Seoul, South Korea

Location

MeSH Terms

Conditions

Sarcoma

Interventions

Heavy Ion Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: November 26, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: November 26, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)