SBRT Plus Systemic Therapy vs Systemic Therapy Alone in BCLC C Hepatocellular Carcinoma

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.

Eligibility

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.

Conditions5

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