Hepatocellular Carcinoma (HCC)NCT07537959
Surgery Plus Systemic Therapy for Liver Cancer With Extrahepatic Metastases
A study testing Primary Tumor Resection and Protocol-Allowed First-Line Immune-Based Systemic Therapy in people with Hepatocellular Carcinoma (HCC) and Metastasis, run by Tongji Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma (HCC), Metastasis
- What is being tested?
- Primary Tumor Resection and Protocol-Allowed First-Line Immune-Based Systemic Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 280 participants
- Where
- 1 siteChina
- Study dates
- 30 Apr 2026to 30 Apr 2031
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430030
About this study
Official title: Primary Tumor Resection Plus Systemic Therapy Versus Systemic Therapy Alone in Hepatocellular Carcinoma With Extrahepatic Metastases: A Multicenter Prospective Randomized Controlled Trial
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.
Read the 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
- Being tested
- Primary Tumor Resection, Protocol-Allowed First-Line Immune-Based Systemic Therapy
- Keywords
- Hepatocellular Carcinoma, Extrahepatic Metastases, Primary Tumor Resection, Systemic Therapy, Immunotherapy
- Medical subject headings
- Carcinoma, Hepatocellular, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Primary Tumor ResectionProcedure or surgery
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.
Protocol-Allowed First-Line Immune-Based Systemic TherapyOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: Primary Tumor Resection; Other: Protocol-Allowed First-Line Immune-Based Systemic Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Overall survival is defined as the time from randomization to death from any cause.
Measured: From randomization until death from any cause, assessed up to 60 months
Secondary outcomes (3)
Progression-Free Survival
Progression-free survival is defined as the time from randomization to disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first.
Measured: From randomization until radiographic disease progression or death, assessed up to 60 months
Objective Response Rate
Objective response rate is defined as the proportion of participants with a best overall response of complete response or partial response according to RECIST version 1.1. In the experimental arm, lesions planned for resection are not selected as baseline target lesions.
Measured: Assessed from randomization through disease progression, up to 60 months
Disease Control Rate
Disease control rate is defined as the proportion of participants with complete response, partial response, or stable disease according to RECIST version 1.1.
Measured: Assessed from randomization through disease progression, up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2026
- Study start30 Apr 2026 (estimated)
- Primary completion30 Apr 2026 (estimated)
- Study completion30 Apr 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular Carcinoma (HCC)Studies of the same condition, open and under way.
- More trials run by Tongji HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 280 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tongji Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chen Xiaoping, Tongji Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07537959
- Sponsor's protocol ID
- EHMS-101
- Status last verified
- Apr 2026
- First submitted
- 12 Apr 2026
- Last updated
- 17 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Primary Tumor Resection Plus Systemic Therapy Versus Systemic Therapy Alone in Hepatocellular Carcinoma With Extrahepatic Metastases: A Multicenter Prospective Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07537959
- Acronym / sponsor ID
- EHMS-101
- Conditions
- Hepatocellular Carcinoma (HCC), Metastasis
- Keywords
- Hepatocellular Carcinoma, Extrahepatic Metastases, Primary Tumor Resection, Systemic Therapy, Immunotherapy
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 280 participants (estimated)
- Lead sponsor
- Tongji HospitalUniversity, hospital or other
- Study start
- 30 Apr 2026 (estimated)
- Primary completion
- 30 Apr 2026 (estimated)
- Study completion
- 30 Apr 2031 (estimated)
- First posted
- 17 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Systemic Therapy Alone | Active comparator | Other: Protocol-Allowed First-Line Immune-Based Systemic TherapyParticipants 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. |
| Primary Tumor Resection Plus Systemic Therapy | Experimental | Procedure: Primary Tumor Resection, Other: Protocol-Allowed First-Line Immune-Based Systemic TherapyParticipants 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Primary Tumor ResectionSurgical 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. | Procedure or surgery | Primary Tumor Resection Plus Systemic Therapy |
| Protocol-Allowed First-Line Immune-Based Systemic TherapyGuideline-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. | Other | Primary Tumor Resection Plus Systemic Therapy, Systemic Therapy Alone |
Primary outcome
Overall Survival
Time frame: From randomization until death from any cause, assessed up to 60 months
Overall survival is defined as the time from randomization to death from any cause.
3 secondary outcomes
Progression-Free Survival
Time frame: From randomization until radiographic disease progression or death, assessed up to 60 months
Objective Response Rate
Time frame: Assessed from randomization through disease progression, up to 60 months
Disease Control Rate
Time frame: Assessed from randomization through disease progression, up to 60 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Primary Tumor Resection and Protocol-Allowed First-Line Immune-Based Systemic Therapy in people with Hepatocellular Carcinoma (HCC) and Metastasis, run by Tongji Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 17 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zhao Huang, M.D (+86 13006378908, huangzhao@tjh.tjmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: From randomization until death from any cause, assessed up to 60 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2026.