NCT07537959

Surgery Plus Systemic Therapy for Liver Cancer With Extrahepatic Metastases

Primary Tumor Resection Plus Systemic Therapy Versus Systemic Therapy Alone in Hepatocellular Carcinoma With Extrahepatic Metastases: A Multicenter Prospective Randomized Controlled Trial

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 280 (estimated)
• Sponsor: Tongji Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This study will evaluate whether resection of the primary liver tumor, in addition to standard first-line systemic therapy, improves survival in patients with hepatocellular carcinoma that has spread outside the liver but still has a resectable primary intrahepatic tumor. Participants will be randomly assigned to receive either primary tumor resection followed by protocol-allowed first-line immune-based systemic therapy or systemic therapy alone. The primary outcome is overall survival. Secondary outcomes include progression-free survival, objective response rate, disease control rate, immune-related adverse events, postoperative complications, and quality of life.

Detailed description

This is a multicenter, prospective, open-label, randomized, parallel-group controlled trial in patients with hepatocellular carcinoma (HCC) with extrahepatic metastases whose primary intrahepatic tumor is considered resectable with curative intent (R0 intent). A total of 280 participants will be randomized in a 1:1 ratio to either primary tumor resection plus protocol-allowed first-line systemic therapy or systemic therapy alone. Randomization will be performed using block randomization with a block size of 4 through a centralized system managed by an independent data management team. Stratification factors include maximum tumor diameter (\<5 cm vs. \>=5 cm), category of systemic therapy (immunotherapy plus anti-angiogenic therapy vs. immunotherapy plus targeted therapy), and liver function status (Child-Pugh A vs. B7). All participants will receive guideline-concordant first-line immune-based systemic therapy. Preferred regimens include PD-1/PD-L1 inhibitor plus anti-angiogenic therapy. PD-1 inhibitor plus multikinase targeted therapy is allowed when anti-angiogenic therapy is contraindicated or not feasible. The use of more than one PD-1/PD-L1 agent in combination is not permitted. Optional hepatic arterial infusion chemotherapy (HAIC) may be used according to clinical need in either arm and will be recorded for exploratory and adjusted analyses. In the experimental arm, participants will undergo resection of the primary liver tumor before systemic therapy. The surgical goal is R0 resection, and the procedure may be anatomic or non-anatomic hepatectomy based on tumor location, liver reserve, and operative risk. Systemic therapy will be initiated after adequate postoperative recovery. In the control arm, participants will receive systemic therapy alone. If a participant in the control arm later becomes a candidate for surgery, such surgery will be recorded as an unplanned intervention, but the participant will remain in the originally assigned group for the primary intention-to-treat analysis. Tumor response will be assessed by contrast-enhanced CT or MRI according to RECIST version 1.1. Imaging will be performed every 6 weeks through week 54 and every 9 weeks thereafter until disease progression or treatment discontinuation. To preserve comparability of response assessment between the two arms, lesions planned for resection in the experimental arm will not be selected as target lesions at baseline. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, objective response rate, disease control rate, postoperative complications of Clavien-Dindo grade II or higher, incidence of immune-related adverse events, and change in quality of life measured by the EORTC QLQ-C30 questionnaire.

Conditions

• Hepatocellular Carcinoma (HCC)
• Metastasis

Interventions

Type	Name	Description
PROCEDURE	Primary Tumor Resection	Surgical resection of the primary liver tumor with curative intent (R0 intent), using anatomic or non-anatomic hepatectomy as appropriate based on tumor location, liver reserve, and operative risk.
OTHER	Protocol-Allowed First-Line Immune-Based Systemic Therapy	Guideline-concordant first-line immune-based systemic therapy. Preferred regimens include PD-1/PD-L1 inhibitor plus anti-angiogenic therapy. PD-1 inhibitor plus multikinase targeted therapy is allowed when anti-angiogenic therapy is contraindicated or not feasible. Concurrent use of more than one PD-1/PD-L1 agent is not permitted.

Timeline

• Start date: 2026-04-30
• Primary completion: 2026-04-30
• Completion: 2031-04-30
• First posted: 2026-04-17
• Last updated: 2026-04-17

Locations

1 site across 1 country: China