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)

Overview

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.

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.

Interventions

• 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

Primary outcome measures

• Objective Response Rate (ORR) [Time frame: Up to 6 months after completion of carbon ion radiotherapy]

Secondary outcome measures (5)

• Progression-free survival (PFS) [Time frame: Up to 3 years after initiation of carbon ion radiotherapy]
• Overall Survival (OS) [Time frame: Up to 3 years after initiation of carbon ion radiotherapy]
• Time to overall tumor progression (TTP) [Time frame: Up to 3 years after initiation of carbon ion radiotherapy]
• Time to local progression [Time frame: Up to 3 years after initiation of carbon ion radiotherapy]
• Treatment-related toxicity [Time frame: From treatment initiation through 30 days post-treatment, or until the next alternative therapy]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

South Korea · 1 center

• Yonsei University Health System, Severance Hospital — Seoul

Identifiers

NCT: NCT07252323 · 4-2024-1588

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗