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

Shandong First Medical University

Status and phase: Enrolling; Phase 2

Conditions: BCLC Stage C Hepatocellular Carcinoma; Hepatocellular Carcinoma

Treatments: Radiation: Radiotherapy; Drug: Systemic therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT07274774

SDZLEC2025-074-02

Details and patient eligibility

About

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.

Full 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.

Enrollment: 184 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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184 participants in 2 patient groups

Treatment

Experimental group

Description:

SBRT + Systemic Therapy

Treatment:

Radiation: Radiotherapy

Drug: Systemic therapy

Control

Other group

Description:

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.

Treatment:

Drug: Systemic therapy