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

Systemic Therapy Combined With Stereotactic Body Radiotherapy Versus Systemic Therapy Alone in BCLC Stage C Hepatocellular Carcinoma (SCRATCH): A Prospective, Multicenter, Phase II, Randomized Controlled Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma; BCLC Stage C Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Systemic therapy; Radiation: Radiotherapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 184
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jinbo Yue, Doctor; Phone Number: 0531-67626442; Email: jbyue@sdfmu.edu.cn

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China
      • Recruiting
      • Shandong Cancer Hospital and Institute
      • Contact: Jinbo Yue, Doctor; Phone Number: 0531-67626442; Email: jbyue@sdfmu.edu.cn
      • Contact: Jinbo Yue, Doctor; Email: jbyue@sdfmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; SBRT + Systemic Therapy	Drug: 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; Radiation: 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.
Other: 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.	Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time from date of randomization to date of death from any cause	subjects will be followed up for a minimum combined accrual + follow-up period of 48 months (24-month enrollment + 24-month follow-up planned)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	Time from randomization to radiographic disease progression per RECIST 1.1/mRECIST or death	2 years
Objective Response Rate (ORR)	proportion achieving CR or PR by RECIST 1.1 and mRECIST; assessed at scheduled imaging	2 years
Disease Control Rate (DCR)	proportion achieving CR + PR + SD	2 years
Duration of Response (DoR)	from first documented CR/PR to progression or death	2 years
Quality of Life (QoL)	baseline and every 3 months using EORTC QLQ-C30	3 years
Quality of Life (QoL)	baseline and every 3 months using EORTC QLQ-HCC18	3 years
Treatment-Related Adverse Events (AEs)	from consent through 30 days after last radiotherapy (Serious Adverse Event reporting up to 90 days post-radiotherapy)	3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patterns of Failure (exploratory)	description of local vs distant progression and subsequent treatments.	2 years
Biomarker (exploratory): Hepatitis B Virus DNA Level	Quantitative assessment of HBV DNA in peripheral blood as a marker of viral replication.	2 years
Biomarker (exploratory): Alpha-fetoprotein (AFP) Level	Serum AFP concentration measured as a tumor burden indicator.	2 years
Biomarker (exploratory): Circulating Tumor DNA (ctDNA) Level	Quantification of tumor-derived DNA fragments in peripheral blood using next-generation sequencing.	2 years
Biomarker (exploratory): Peripheral Immune Cell Subsets	Flow cytometry-based analysis of circulating immune cell populations	2 years
Biomarker (exploratory): ALBI grade	ALBI grade assessed as indicators of survival	2 years

Collaborators and Investigators

• Sponsor: Shandong Cancer Hospital and Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2025
• Primary Completion (Estimated): November 10, 2027
• Study Completion (Estimated): November 10, 2028

Study Registration Dates

• First Submitted: November 22, 2025
• First Submitted That Met QC Criteria: December 9, 2025
• First Posted (Actual): December 10, 2025

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: hepatocellular carcinoma; metastasis; radiotheraphy; BCLC stage C
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Neoplastic Processes; Carcinoma; Pathological Conditions, Signs and Symptoms; Carcinoma, Hepatocellular; Neoplasm Metastasis; Therapeutics; Radiotherapy
• Other Study ID Numbers: SDZLEC2025-074-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No