Unresectable Hepatocellular CarcinomaNCT06280313
Impact of Splenectomy on the Efficacy of Targeted Therapy and Immunotherapy in Unresectable HCC Patients With Cirrhotic Portal Hypertension
An observational study of Unresectable Hepatocellular Carcinoma, run by Zhiyong Huang at 1 site in China.
Trial summary
Currently, the combination of targeted therapy and immunotherapy is the first-line treatment for advanced hepatocellular carcinoma (HCC). However, a subset of HCC patients with severe splenomegaly, splenic hyperfunction, and esophagogastric varices due to liver cirrhosis and portal hypertension may be unable to… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Unresectable Hepatocellular Carcinoma
- What is being tested?
- Splenectomy+Targeted therapy+ Immunotherapy
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 15 Mar 2024to 15 Mar 2028
- Phase
- Observational
- 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
Study population: Unresectable HCC patients with cirrhotic portal hypertension
Who may be able to join
- Patients aged 18 to 75 years (inclusive).
- No prior systemic antitumor treatment or meeting the criteria for splenectomy during treatment.
- Clinical or pathological diagnosis of hepatocellular carcinoma (HCC) that is unresectable initially or has recurred after surgery.
- HBV-DNA less than 1*10^5 copies/ml and undergoing antiviral therapy.
- ECOG performance status score of 0-1, without significant organ dysfunction.
- Child-Pugh score of 5-7.
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- Spleen thickness >4.0 cm.
- History of esophagogastric varices, red signs, or variceal bleeding with or without splenomegaly.
- Splenomegaly with WBC <2.5 × 10^9/L and PLT <70 × 10^9/L, or splenomegaly with WBC <2.0 × 10^9/L or PLT <50 × 10^9/L.
- Important organ functions meeting the following criteria: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3*ULN, total bilirubin ≤ 3*ULN; International normalized ratio (INR) ≤ 1.5*ULN; prothrombin time ≤ 1.5*ULN; creatinine ≤ 1.5*ULN.
- Able to undergo local treatments such as transarterial chemoembolization (TACE), hepatic artery infusion chemotherapy (HAIC), selective internal radiation therapy with yttrium-90 (SIRT), stereotactic body radiation therapy (SBRT), and ablation (including radiofrequency ablation (RFA) and microwave ablation (MWA)).
- Willing to provide informed consent.
- Expected survival time of more than 3 months.
Who cannot join
- History of or concurrent active malignancy (excluding malignancies that have been cured for over 5 years or in situ cancers that can be completely cured with adequate treatment).
- Presence of central nervous system metastasis or a history of brain metastasis.
- History of organ transplantation.
- History of surgery in the head, chest, or abdomen within the past six months.
- Child-Pugh class C liver function or significant ascites.
- Marked thrombosis in the portal venous system or extensive cancer thrombus in the main portal vein.
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- Activated partial thromboplastin time (APTT) or prothrombin time (PT) exceeding 1.5 times the upper limit of normal (as per the normal values of the clinical trial research center), or evidence of bleeding tendency or history of bleeding within the two months prior to enrollment, regardless of severity.
- Ongoing active infection within 7 days after completion of systemic antibiotic therapy.
- Active coronary artery disease, severe/unstable angina, or newly diagnosed angina or myocardial infarction within the past 12 months before enrollment.
- Thrombotic or embolic events within the past 12 months, such as cerebrovascular accidents (including transient ischemic attacks), pulmonary embolism, or deep vein thrombosis.
- New York Heart Association (NYHA) class II or above congestive heart failure.
- Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), positive syphilis serology, untreated active hepatitis (defined as HBV-DNA ≥ 10^5 copies/ml; HCV-RNA higher than the lower limit of detection for the assay).
- Any active, known, or suspected autoimmune disease. Stable subjects not requiring systemic immunosuppressive therapy may be included, such as those with type 1 diabetes, hypothyroidism requiring only hormone replacement therapy, and skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis, and alopecia).
- Interstitial lung disease, non-infectious pneumonia, or uncontrolled systemic diseases (e.g., diabetes, hypertension, pulmonary fibrosis, and acute pneumonia).
- Pregnant or lactating women or females with a positive pregnancy test prior to the first dose who have the potential for pregnancy.
- The investigator deems the subject inappropriate for participation in this clinical study due to any clinical or laboratory abnormalities or compliance issues.
- Severe psychological or mental abnormalities.
- Participation in another drug clinical trial within the past 4 weeks.
- Other reasons that the investigator considers unsuitable for enrollment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Erlei Zhang contact
China1 site, 1 recruiting
- Recruiting
Tongji Hospital
Wuhan, Hubei, 430000
Zhiyong Huang, 86-13995507729, Zyhuang126@126.com
Erlei Zhang, baiyu19861104@163.com
About this study
Currently, the combination of targeted therapy and immunotherapy is the first-line treatment for advanced hepatocellular carcinoma (HCC). However, a subset of HCC patients with severe splenomegaly, splenic hyperfunction, and esophagogastric varices due to liver cirrhosis and portal hypertension may be unable to undergo or sustain the combination therapy, ultimately missing the optimal treatment window. Prior studies have indicated that splenectomy can significantly improve liver function and hepatic reserve in cirrhotic patients. It also addresses splenic hyperfunction and reduces the risk of bleeding from esophagogastric varices by combining splenectomy with devascularization around the cardia. Additionally, splenectomy contributes to the improvement of liver fibrosis and restoration of immune function in cirrhotic patients. This study aims to elucidate the impact of splenectomy on the efficacy of combination targeted and immunotherapy in unresectable HCC patients with cirrhotic portal hypertension, particularly those with poor liver function, significant splenic hyperfunction, and severe esophagogastric varices. The research also seeks to explore whether changes in the tumor immune microenvironment before and after splenectomy can influence the effectiveness of immunotherapy. Ultimately, the goal is to provide therapeutic opportunities for this specific patient population.
Read the detailed description
This is a single-arm, open-label, observational study assessing the impact of splenectomy on the efficacy of combined targeted and immune therapy in patients with unresectable hepatocellular carcinoma accompanied by cirrhotic portal hypertension. Eligible patients with unresectable hepatocellular carcinoma were enrolled in the trial, and all participants underwent either open or laparoscopic splenectomy, with or without devascularization around the cardia. Starting two weeks post-surgery, patients began intravenous infusion of PD-1 monoclonal antibody, Tislelizumab, at a dosage of 200mg every three weeks. Three weeks post-surgery, patients commenced oral administration of the targeted therapy, Lenvatinib, with a dosage based on body weight: 8mg (≤60kg) or 12mg (>60kg), once daily. The use of Tislelizumab and Lenvatinib continued until the primary endpoint, which was disease progression, intolerable toxicity reactions, or other criteria specified in the protocol for terminating the study treatment.
- Conditions
- Unresectable Hepatocellular Carcinoma
- Being tested
- Splenectomy+Targeted therapy+ Immunotherapy
- Keywords
- Immunotherapy, Targeted therapy, Splenectomy, HCC
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Splenectomy+Targeted therapy+ ImmunotherapyCombination product
Eligible patients with unresectable hepatocellular carcinoma accompanied by cirrhotic portal hypertension were enrolled in the trial, and all participants underwent either open or laparoscopic splenectomy, with or without devascularization around the cardia. Starting two weeks post-surgery, patients began intravenous infusion of PD-1 monoclonal antibody, Tislelizumab, at a dosage of 200mg every three weeks. Three weeks post-surgery, patients commenced oral administration of the targeted therapy, Lenvatinib, with a dosage based on body weight: 8mg (≤60kg) or 12mg (>60kg), once daily.
| Study group | Role | What they receive |
|---|---|---|
| Treatment (Splenectomy+Targeted therapy+ Immunotherapy) | Eligible patients with unresectable hepatocellular carcinoma accompanied by cirrhotic portal hypertension were enrolled in the trial, and all participants underwent either open or laparoscopic splenectomy, with or without devascularization around the cardia. Starting two weeks post-surgery, patients began intravenous infusion of PD-1 monoclonal antibody, Tislelizumab, at a dosage of 200mg every three weeks. Three weeks post-surgery, patients commenced oral administration of the targeted therapy, Lenvatinib, with a dosage based on body weight: 8mg (≤60kg) or 12mg (>60kg), once daily. Receives: Combination Product: Splenectomy+Targeted therapy+ Immunotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
ORR refers to the proportion of patients whose tumors shrink to a certain amount and maintain for a certain period of time (6 weeks after first dose of Tislelizumab), including CR+PR cases. CR (complete remission): disappearance of all target lesions, PR (partial remission): reduction of the sum of the length and diameter of the baseline lesions by ≥30%
Measured: 6 weeks after first dose of Tislelizumab
Secondary outcomes (2)
Overall Survival (OS)
OS was defined as time from diagnosis to death from any cause or the last follow-up
Measured: through study completion, an average of 2 year
Progression Free Survival (PFS)
PFS refers to the time from subject enrollment to disease progression according the Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1) or death
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2024
- Study start15 Mar 2024
- Primary completion15 Mar 2027 (estimated)
- Study completion15 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unresectable Hepatocellular CarcinomaStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhiyong Huang
- Sponsor type
- University, hospital or other
- Collaborators
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Zhongnan Hospital, Renmin Hospital of Wuhan University, Taihe Hospital, Hubei Cancer Hospital, Xiangyang Central Hospital, Wuhan Central Hospital, Yichang Third Renmin Hospital
- Responsible party
- Sponsor-investigator, Zhiyong Huang, Tongji Hospital
- Investigators
- Zhiyong Huang, Principal investigator, Tongji Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06280313
- Sponsor's protocol ID
- uHCC-STI-TJ01
- Status last verified
- Aug 2025
- First submitted
- 20 Feb 2024
- Last updated
- 15 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Splenectomy on the Efficacy of Targeted Therapy and Immunotherapy in Unresectable HCC Patients With Cirrhotic Portal Hypertension
- ClinicalTrials.gov ID
- NCT06280313
- Acronym / sponsor ID
- uHCC-STI-TJ01
- Conditions
- Unresectable Hepatocellular Carcinoma
- Keywords
- Immunotherapy, Targeted therapy, Splenectomy, HCC
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Zhiyong HuangUniversity, hospital or other
- Collaborators
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Zhongnan Hospital, Renmin Hospital of Wuhan University, Taihe Hospital, Hubei Cancer Hospital, Xiangyang Central Hospital, Wuhan Central Hospital, Yichang Third Renmin Hospital
- Study start
- 15 Mar 2024 (actual)
- Primary completion
- 15 Mar 2027 (estimated)
- Study completion
- 15 Mar 2028 (estimated)
- First posted
- 28 Feb 2024 (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.
Currently, the combination of targeted therapy and immunotherapy is the first-line treatment for advanced hepatocellular carcinoma (HCC). However, a subset of HCC patients with severe splenomegaly, splenic hyperfunction, and esophagogastric varices due to liver cirrhosis and portal hypertension may be unable to undergo or sustain the combination therapy, ultimately missing the optimal treatment window. Prior studies have indicated that splenectomy can significantly improve liver function and hepatic reserve in cirrhotic patients. It also addresses splenic hyperfunction and reduces the risk of bleeding from esophagogastric varices by combining splenectomy with devascularization around the cardia. Additionally, splenectomy contributes to the improvement of liver fibrosis and restoration of immune function in cirrhotic patients. This study aims to elucidate the impact of splenectomy on the efficacy of combination targeted and immunotherapy in unresectable HCC patients with cirrhotic portal hypertension, particularly those with poor liver function, significant splenic hyperfunction, and severe esophagogastric varices. The research also seeks to explore whether changes in the tumor immune microenvironment before and after splenectomy can influence the effectiveness of immunotherapy. Ultimately, the goal is to provide therapeutic opportunities for this specific patient population.
Detailed description
This is a single-arm, open-label, observational study assessing the impact of splenectomy on the efficacy of combined targeted and immune therapy in patients with unresectable hepatocellular carcinoma accompanied by cirrhotic portal hypertension. Eligible patients with unresectable hepatocellular carcinoma were enrolled in the trial, and all participants underwent either open or laparoscopic splenectomy, with or without devascularization around the cardia. Starting two weeks post-surgery, patients began intravenous infusion of PD-1 monoclonal antibody, Tislelizumab, at a dosage of 200mg every three weeks. Three weeks post-surgery, patients commenced oral administration of the targeted therapy, Lenvatinib, with a dosage based on body weight: 8mg (≤60kg) or 12mg (>60kg), once daily. The use of Tislelizumab and Lenvatinib continued until the primary endpoint, which was disease progression, intolerable toxicity reactions, or other criteria specified in the protocol for terminating the study treatment.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (Splenectomy+Targeted therapy+ Immunotherapy) | – | Combination Product: Splenectomy+Targeted therapy+ ImmunotherapyEligible patients with unresectable hepatocellular carcinoma accompanied by cirrhotic portal hypertension were enrolled in the trial, and all participants underwent either open or laparoscopic splenectomy, with or without devascularization around the cardia. Starting two weeks post-surgery, patients began intravenous infusion of PD-1 monoclonal antibody, Tislelizumab, at a dosage of 200mg every three weeks. Three weeks post-surgery, patients commenced oral administration of the targeted therapy, Lenvatinib, with a dosage based on body weight: 8mg (≤60kg) or 12mg (>60kg), once daily. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Unresectable HCC patients with cirrhotic portal hypertension
Key inclusion criteria (13 listed)
- Patients aged 18 to 75 years (inclusive).
- No prior systemic antitumor treatment or meeting the criteria for splenectomy during treatment.
- Clinical or pathological diagnosis of hepatocellular carcinoma (HCC) that is unresectable initially or has recurred after surgery.
- HBV-DNA less than 1*10^5 copies/ml and undergoing antiviral therapy.
- ECOG performance status score of 0-1, without significant organ dysfunction.
Key exclusion criteria (19 listed)
- History of or concurrent active malignancy (excluding malignancies that have been cured for over 5 years or in situ cancers that can be completely cured with adequate treatment).
- Presence of central nervous system metastasis or a history of brain metastasis.
- History of organ transplantation.
- History of surgery in the head, chest, or abdomen within the past six months.
- Child-Pugh class C liver function or significant ascites.
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 |
|---|---|---|
| Splenectomy+Targeted therapy+ ImmunotherapyEligible patients with unresectable hepatocellular carcinoma accompanied by cirrhotic portal hypertension were enrolled in the trial, and all participants underwent either open or laparoscopic splenectomy, with or without devascularization around the cardia. Starting two weeks post-surgery, patients began intravenous infusion of PD-1 monoclonal antibody, Tislelizumab, at a dosage of 200mg every three weeks. Three weeks post-surgery, patients commenced oral administration of the targeted therapy, Lenvatinib, with a dosage based on body weight: 8mg (≤60kg) or 12mg (>60kg), once daily. | Combination product | Treatment (Splenectomy+Targeted therapy+ Immunotherapy) |
Primary outcome
Objective Response Rate (ORR)
Time frame: 6 weeks after first dose of Tislelizumab
ORR refers to the proportion of patients whose tumors shrink to a certain amount and maintain for a certain period of time (6 weeks after first dose of Tislelizumab), including CR+PR cases. CR (complete remission): disappearance of all target lesions, PR (partial remission): reduction of the sum of the length and diameter of the baseline lesions by ≥30%
2 secondary outcomes
Overall Survival (OS)
Time frame: through study completion, an average of 2 year
Progression Free Survival (PFS)
Time frame: 18 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 15 Aug 2025.
- Individual participant dataSharing planned: No
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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.
Erlei Zhang contact
Zhiyong Huang principal investigator
Tongji Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Unresectable Hepatocellular Carcinoma, run by Zhiyong Huang 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 13 inclusion and 19 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: looking for participants now, as of the sponsor's last update on 15 Aug 2025. 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 Zhiyong Huang (86-13995507729, Zyhuang126@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: 6 weeks after first dose of Tislelizumab). 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 15 Aug 2025.