Surgery Plus Systemic Therapy for Liver Cancer With Extrahepatic Metastases

NCT07537959 | Not Yet Recruiting DMC

• 1 other identifier: EHMS-101
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hepatocellular Carcinoma (HCC); Metastasis

Keywords

Hepatocellular Carcinoma; Extrahepatic Metastases; Primary Tumor Resection; Systemic Therapy; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Overall survival is defined as the time from randomization to death from any cause.

  From randomization until death from any cause, assessed up to 60 months

Secondary Outcomes (3)

• Progression-Free Survival

  From randomization until radiographic disease progression or death, assessed up to 60 months

• Objective Response Rate

  Assessed from randomization through disease progression, up to 60 months

• Disease Control Rate

  Assessed from randomization through disease progression, up to 60 months

Study Arms (2)

Systemic Therapy Alone

ACTIVE COMPARATOR

Participants receive protocol-allowed first-line immune-based systemic therapy without planned primary tumor resection. Optional HAIC may be used according to clinical need and will be recorded. Unplanned surgery after randomization will be recorded but will not change the original group assignment for the primary analysis.

Other: Protocol-Allowed First-Line Immune-Based Systemic Therapy

Primary Tumor Resection Plus Systemic Therapy

EXPERIMENTAL

Participants undergo resection of the primary intrahepatic tumor with curative intent (R0 intent) followed by protocol-allowed first-line immune-based systemic therapy after adequate postoperative recovery. Optional HAIC may be used according to clinical need and will be recorded.

Procedure: Primary Tumor Resection; Other: Protocol-Allowed First-Line Immune-Based Systemic Therapy

Interventions

Primary Tumor Resection PROCEDURE

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.

Primary Tumor Resection Plus Systemic Therapy

Protocol-Allowed First-Line Immune-Based Systemic Therapy OTHER

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.

Primary Tumor Resection Plus Systemic Therapy; Systemic Therapy Alone

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 75 years
• Hepatocellular carcinoma confirmed by imaging and/or histology according to AASLD or EASL criteria
• Resectable primary intrahepatic tumor with expected R0 resection
• ECOG performance status 0 to 1
• At least one measurable extrahepatic metastatic lesion according to RECIST version 1.1
• Child-Pugh class A or stable Child-Pugh B7
• Written informed consent and willingness to comply with study follow-up and data collection

You may not qualify if:

• Prior systemic therapy for hepatocellular carcinoma, including immunotherapy, targeted therapy, or chemotherapy
• Decompensated or clinically unstable liver disease, including refractory ascites, recurrent hepatic encephalopathy, active gastrointestinal bleeding, or - Child-Pugh class greater than B7
• Major bleeding risk or clinically significant coagulation abnormality, including recent gastrointestinal bleeding or untreated/high-risk gastroesophageal varices
• Active autoimmune disease or long-term systemic immunosuppressive therapy
• Active severe infection, including uncontrolled bacterial or fungal infection, uncontrolled hepatitis B virus replication without appropriate antiviral treatment, or active tuberculosis
• Uncontrolled central nervous system metastases
• Uncontrolled cardiovascular disease, including poorly controlled hypertension, recent myocardial infarction, unstable angina, stroke, or major thrombotic event
• Significant proteinuria or renal dysfunction considered unsuitable for study treatment
• Another active malignancy, except for selected low-risk malignancies allowed by the investigator and ethics committee
• Pregnancy or breastfeeding
• Known severe hypersensitivity to study-related drugs
• Poor compliance, psychiatric or cognitive disorder preventing study participation, or any other condition judged by the investigator to make the participant unsuitable for the trial

Sponsors & Collaborators

• Tongji Hospital: lead

Study Sites (1)

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430030, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Zhao Huang, M.D

CONTACT

+86 13006378908; huangzhao@tjh.tjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label trial because the intervention includes surgery and cannot be masked to participants or investigators.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Model Details: Participants are randomized in a 1:1 ratio to receive either primary tumor resection plus protocol-allowed first-line immune-based systemic therapy or protocol-allowed first-line immune-based systemic therapy alone.

Study Record Dates

• First Submitted: April 12, 2026
• First Posted: April 17, 2026
• Study Start: April 30, 2026
• Primary Completion: April 30, 2026
• Study Completion (Estimated): April 30, 2031
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

CN (1)