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

NCT ID: NCT07274774

Last Updated: 2025-12-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 184 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-30
• Study Completion Date: 2028-11-10

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.

Conditions

Hepatocellular Carcinoma; BCLC Stage C Hepatocellular Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

SBRT + Systemic Therapy

Group Type: EXPERIMENTAL

Radiotherapy

Intervention Type: RADIATION

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.

Systemic therapy

Intervention Type: DRUG

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

Control

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.

Group Type: OTHER

Systemic therapy

Intervention Type: DRUG

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

Interventions

Radiotherapy

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.

Intervention Type: RADIATION

Systemic 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

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Shandong Cancer Hospital and Institute

OTHER

Sponsor Role: lead

Responsible Party

Jinbo Yue

Director of Department Radiation Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Shandong Cancer Hospital and Institute

Jinan, Shandong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jinbo Yue, doctor

Role: CONTACT

jbyue@sdfmu.edu.cn

0531-67626442

Facility Contacts

Jinbo Yue, doctor

Role: primary

jbyue@sdfmu.edu.cn

0531-67626442

Jinbo Yue, Doctor

Role: backup

jbyue@sdfmu.edu.cn

Other Identifiers

SDZLEC2025-074-02

Identifier Type: -

Identifier Source: org_study_id