BCLC Stage C Hepatocellular Carcinoma, Hepatocellular Carcinoma
Conditions
Keywords
hepatocellular carcinoma, BCLC stage C, metastasis, radiotheraphy
Brief summary
This prospective, multicenter, phase II randomized controlled trial compares the efficacy and safety of SBRT combined with systemic therapy versus systemic therapy alone in BCLC stage C hepatocellular carcinoma (HCC). The primary objective is to compare overall survival (OS) between the two arms. Secondary objectives include progression-free survival (PFS), objective response rate (ORR), quality of life (QoL), and incidence and severity of adverse events (AEs). Eligible patients will be randomized 2:1 to an experimental arm (SBRT + systemic therapy) or control arm (systemic therapy alone). Key inclusion criteria include BCLC C disease, Child-Pugh A-B liver function, ECOG ≤2, measurable disease per RECIST 1.1, and stable intrahepatic disease after initial systemic therapy for ≥3 months when applicable. The trial will also include predefined safety monitoring, QoL assessments (EORTC QLQ-C30 and QLQ-HCC18), and exploratory biomarker analyses.
Detailed description
Background: Hepatocellular carcinoma (HCC) is frequently diagnosed at advanced stages with limited curative options. Systemic therapies (targeted agents and immune checkpoint inhibitors) have improved outcomes in BCLC C patients, but their therapeutic effect is unsatisfactory. SBRT provides precise high-dose local control and may synergize with systemic therapy by enhancing tumor immunogenicity and improving local disease control. Study design: Prospective, randomized, open-label, multicenter Phase II trial. In the experimental arm, patients will continue the guideline-recommended systemic treatment received prior to enrollment, in accordance with approved labels and national guidelines, combined with SBRT delivered to portal vein tumor thrombus (PVTT, if present) and/or limited extrahepatic metastatic lesions. In the control arm, patients will continue the same guideline-recommended systemic treatment without SBRT. Endpoints: The primary endpoint is overall survival (OS). Secondary endpoints include progression-free survival (PFS), objective response rate (ORR by RECIST 1.1 and mRECIST), disease control rate (DCR), duration of response (DoR), quality of life (EORTC QLQ-C30 and QLQ-HCC18), and safety (CTCAE v5.0). Exploratory endpoints may include biomarker dynamics (e.g., immune cell infiltration, viral markers) and patterns of progression. Safety and monitoring: AEs will be collected from consent through 30 days after the last radiotherapy; SAEs will be reported per protocol (including deaths up to 90 days after radiotherapy). Regular imaging and clinical assessments will monitor efficacy and safety. Data management and monitoring will follow GCP.
Interventions
DRUGSystemic therapy
Systemic therapy will consist of the continuation of the guideline-recommended systemic treatment received prior to enrollment, in accordance with approved labels and national guidelines
RADIATIONRadiotherapy
portal vein tumor thrombus (PVTT, if present) and/or limited extrahepatic active lesions. For patients presenting with more than 10 lesions at baseline (including extrahepatic metastases with or without portal vein tumor thrombus), a comprehensive FDG-PET/CT reassessment of the whole body is required after 3 months of systemic therapy. Patients who demonstrate ≤10 active lesions at this reassessment may then be considered eligible for SBRT. Dose and fractionation: total dose 25-40 Gy delivered in 5 fractions (5-8 Gy per fraction). Dose selection individualized based on tumor size, location and nearby organ-at-risk constraints; sequential or staged SBRT allowed.
Sponsors
Shandong Cancer Hospital and Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age 18-70 years. 2. Histologically or clinically diagnosed HCC per national guidelines. 3. BCLC stage C (CNLC IIIA/IIIB), including PVTT and/or extrahepatic metastases amenable to protocol procedures. 4. Child-Pugh class A or B (score ≤7). 5. At least one measurable lesion per RECIST 1.1 (criteria specified). 6. ECOG ≤2. 7. Expected survival ≥6 months. 8. Adequate organ function per protocol thresholds. 9. For experimental arm candidates: active lesion count (when PET-CT used) ≤10. 10. If prior initial systemic therapy given: intrahepatic disease stable ≥3 months. 11. Effective contraception from consent through 1 year after treatment end. 12. Ability to understand and sign consent.
Exclusion criteria
1. Second primary malignancy (exceptions apply). 2. Tumor thrombus/metastases judged not amenable to radiotherapy. 3. Prior systemic anticancer therapy for current HCC (prior local therapy permitted per rules). 4. Severe organ dysfunction precluding treatment. 5. Uncontrolled comorbidities (e.g., uncontrolled diabetes, active peptic ulcer, severe cardiopulmonary disease). 6. Active uncontrolled infection or active autoimmune disease requiring systemic therapy. 7. Significant neurologic dysfunction. 8. Pregnant or breastfeeding women; no effective contraception. 9. Known hypersensitivity to planned drugs. 10. Any other condition making participation unsuitable per investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | subjects will be followed up for a minimum combined accrual + follow-up period of 48 months (24-month enrollment + 24-month follow-up planned) | Time from date of randomization to date of death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | 2 years | Time from randomization to radiographic disease progression per RECIST 1.1/mRECIST or death |
| Objective Response Rate (ORR) | 2 years | proportion achieving CR or PR by RECIST 1.1 and mRECIST; assessed at scheduled imaging |
| Disease Control Rate (DCR) | 2 years | proportion achieving CR + PR + SD |
| Duration of Response (DoR) | 2 years | from first documented CR/PR to progression or death |
| Quality of Life (QoL) | 3 years | baseline and every 3 months using EORTC QLQ-C30 |
| Treatment-Related Adverse Events (AEs) | 3 months | from consent through 30 days after last radiotherapy (Serious Adverse Event reporting up to 90 days post-radiotherapy) |
Countries
China
Contacts
CONTACTJinbo Yue, doctor
Outcome results
None listed