This single-center, prospective phase II clinical trial evaluates the safety and therapeutic efficacy of combining carbon ion radiotherapy with the standard first-line regimen of atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma. The study aims to determine whether the addition of carbon ion radiotherapy enhances tumor control and improves clinical outcomes beyond those achieved with systemic therapy alone. Key endpoints include overall survival, progression-free survival, objective response rate, and treatment-related adverse events.
Age ≥ 18 years Histologically or radiologically confirmed hepatocellular carcinoma (HCC) Barcelona Clinic Liver Cancer (BCLC) stage B or C, not eligible for curative surgery or transplantation.
Prior systemic therapy with anti-PD-1, anti-PD-L1, or anti-VEGF agents within the past year.
Single group
Carbon Ion Radiotherapy Atezolizumab Bevacizumab
RadiationParticipants will initiate systemic therapy with atezolizumab (1200 mg IV every 3 weeks) and bevacizumab (15 mg/kg IV every 3 weeks). Carbon ion radiotherapy will subsequently be administered to the primary hepatic lesion during the early phase of systemic therapy. Carbon ion radiotherapy will be delivered using a hypofractionated schedule (approximately 4-12 fractions), with dose and fractionation individualized based on tumor size, anatomical location, and organ-at-risk considerations. After completion of carbon ion radiotherapy, participants will continue maintenance treatment with atezolizumab and bevacizumab until disease progression or unacceptable toxicity.
Progression-Free Survival (PFS)
Progression-free survival is defined as the time from the first administration of atezolizumab plus bevacizumab to the date of documented tumor progression or death from any cause, whichever occurs first.
Overall survival
Overall survival is defined as the time from the first administration of atezolizumab plus bevacizumab to death from any cause. Surviving patients will be censored at the date of the last follow-up. OS defines death or last follow-up date from the date of first AtezoBev administration.
intrahepatic tumor response
Tumor response will be evaluated according to RECIST criteria at predefined time points. Complete Response (CR): Disappearance of all target lesions Partial Response (PR): ≥30% decrease in the sum of the longest diameters of target lesions Progressive Disease (PD): ≥20% increase in the sum of the longest diameters of target lesions, or appearance of new lesions Stable Disease (SD): Does not meet criteria for CR, PR, or PD Disease Control Rate (DCR) will be measured as CR + PR + SD. (ORR = CR + PR / DCR = CR + PR + SD)
rate of achieving curative down-staging
The proportion of patients who become eligible for curative-intent treatments after tumor down-staging will be assessed. Curative treatments may include liver transplantation, hepatic resection, ablation, TACE, or TARE, based on the discretion of the treating physician. How often radical treatments become possible after down-staging A decrease in stage was confirmed during the course of treatment, and treatment targeting the root, such as liver transplantation, hepatic resection, other local ablation, TACE, or TARE, is allowed at the discretion of the physician.
treatment-related toxicity
Treatment-related adverse events will be evaluated and graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Safety follow-up will continue from study entry until 30 days after the final planned dose of protocol treatment, or until initiation of subsequent alternative therapy, whichever occurs first.Toxicity is assessed using the National Cancer Society's Common Criteria for Judgment (NCI-CTC). Patients participating in the treatment are subject to safety and toxicity follow-up from participation in the study to 30 days after the final dose of the treatment under the plan is completed (or until the earliest of the start of the next alternative treatment).
Click on the lead sponsor to view all of their trials.
