A Single-arm Phase II Clinical Study Investigating the Safety and Efficacy of Carbon Ion Radiotherapy in Patients With Hepatocellular Carcinoma Previously Treated With Transarterial Radioembolization (TARE)

This is a prospective, single-arm Phase II study designed to evaluate the safety and efficacy of carbon ion radiotherapy in patients with hepatocellular carcinoma (HCC) who demonstrate residual or recurrent disease after prior transarterial radioembolization (TARE). Carbon ion radiotherapy delivers highly conformal, high-linear energy transfer radiation, enabling dose escalation to hepatic tumors while minimizing exposure to surrounding normal tissues.

Eligible patients will receive carbon ion radiotherapy to target lesions, and clinical outcomes including objective response rate, progression-free survival, overall survival, and treatment-related toxicity will be systematically assessed. The study aims to determine whether carbon ion radiotherapy can provide effective local tumor control and acceptable safety in this population, thereby establishing evidence to guide its therapeutic role following TARE.

Study Overview

• Status: Recruiting
• Conditions: Carcinoma; Hepatocellular Carcinoma
• Intervention / Treatment: Radiation: Carbon Ion Radiotherapy

Detailed Description

This prospective, single-arm Phase II study evaluates the safety and efficacy of carbon ion radiotherapy in patients with hepatocellular carcinoma (HCC) who have residual or recurrent disease after prior transarterial radioembolization (TARE). Although TARE is an important locoregional treatment, some patients exhibit incomplete response or local progression and have limited subsequent therapeutic options.

Carbon ion radiotherapy provides highly conformal dose distribution and increased biological effectiveness, enabling escalation of tumoricidal doses while sparing surrounding liver tissue and adjacent gastrointestinal organs. Eligible patients will undergo baseline assessments and multidisciplinary review to confirm suitability for treatment. Carbon ion radiotherapy will be delivered using hypofractionated regimens individualized based on tumor characteristics and organ-at-risk constraints.

Patients will be followed with scheduled imaging, laboratory tests, and toxicity assessments. Efficacy will be measured through tumor response, local control, progression-free survival, and overall survival. Safety will be evaluated according to CTCAE criteria. The study aims to determine whether carbon ion radiotherapy can serve as an effective and feasible salvage treatment for TARE-refractory or recurrent HCC.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• South Korea
  • Seoul, South Korea
    • Recruiting
    • Yonsei University Health System, Severance Hospital
    • Contact: Ik Jae Lee; Phone Number: +82-2-2228-8117; Email: IKJAE412@YUHS.AC

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• adult patients over the age of 19 Hepatocellular carcinoma patients confirmed imagingly or histologically Patients who have a residual lesion in the TARE-treated area or have a recurrence or progressive lesion in the TARE-treated area or nearby liver and are deemed to need additional treatment when evaluating the response for more than 6 months Child-Pugh Class A (Child-Pugh score 5-6), B (CP score 7) Patients who fall within the range of lesions that can afford the baryon treatment intended in this study Patients who have minimal availability of liver excluded from treatment in terms of preservation of liver function proper liver function Patients with AST/ALT less than 5 times the upper limit of normal If you don't have blood clotting disorder ECOG performance status 2 or lower Patients who are not pregnant or who are undergoing appropriate contraception for women of childbearing age No other underlying conditions that seriously affect survival Patients who have listened to and agreed to a documented explanation and a statement of consent

Exclusion Criteria:

• If you've had external radiotherapy in your liver Patients with unresolved infections at that point Patients who have a current or other history of advanced carcinoma within 5 years a patient who underwent a liver transplant If baryon treatment is inappropriate or dangerous under the judgment of a radiologic oncologist

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Carbon Ion Radiotherapy; Participants will receive carbon ion radiotherapy targeting residual or recurrent hepatocellular carcinoma following prior transarterial radioembolization (TARE). Treatment will be delivered using hypofractionated high-linear energy transfer radiation, with dose and fractionation individualized based on tumor size, anatomical location, and organ-at-risk constraints. The intervention aims to provide effective local tumor control while maintaining acceptable safety in patients who have limited subsequent treatment options after TARE.

Radiation: Carbon Ion Radiotherapy; Carbon ion radiotherapy will be delivered to residual or recurrent hepatocellular carcinoma in patients previously treated with transarterial radioembolization (TARE). Treatment will be administered using hypofractionated high-linear energy transfer radiation, with dose and fractionation individualized based on tumor size, tumor location, and organ-at-risk constraints. The aim of the intervention is to achieve enhanced local tumor control while minimizing toxicity to surrounding normal tissues

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective response rate is defined as the proportion of patients achieving complete response (CR) or partial response (PR) according to mRECIST criteria. Tumor response will be assessed through scheduled imaging studies within 6 months after carbon ion radiotherapy.	Up to 6 months after completion of carbon ion radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS is defined as the time from the start of carbon ion radiotherapy to the first documented disease progression or death from any cause, or to the date of last follow-up.	Up to 3 years after initiation of carbon ion radiotherapy
Overall Survival (OS)	OS is defined as the time from the start of carbon ion radiotherapy to death from any cause, or to the last follow-up date for censored patients.	Up to 3 years after initiation of carbon ion radiotherapy
Time to overall tumor progression (TTP)	TTP is defined as the time from the start of carbon ion radiotherapy to progression of any target or non-target lesion, or the appearance of new intrahepatic or extrahepatic lesions.	Up to 3 years after initiation of carbon ion radiotherapy
Time to local progression	Time to local progression is defined as the interval from the start of carbon ion radiotherapy to radiologic progression within the treated liver area.	Up to 3 years after initiation of carbon ion radiotherapy
Treatment-related toxicity	Toxicity will be evaluated and graded according to CTCAE version 5.0. Toxicity follow-up continues from treatment initiation until confirmation of study completion or until the earliest start of subsequent therapy.	From treatment initiation through 30 days post-treatment, or until the next alternative therapy

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: November 18, 2025
• First Submitted That Met QC Criteria: November 18, 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 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Therapeutics; Radiotherapy; Heavy Ion Radiotherapy
• Other Study ID Numbers: 4-2024-1588

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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