- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06280313
Impact of Splenectomy on the Efficacy of Targeted Therapy and Immunotherapy in Unresectable HCC Patients With Cirrhotic Portal Hypertension
April 9, 2024 updated by: Zhiyong Huang
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
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 Type
Observational
Enrollment (Estimated)
60
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Zhiyong Huang
- Phone Number: 86-13995507729
- Email: Zyhuang126@126.com
Study Contact Backup
- Name: Erlei Zhang
- Email: baiyu19861104@163.com
Study Locations
-
-
Hubei
-
Wuhan, Hubei, China, 430000
- Recruiting
- Tongji Hospital
-
Contact:
- Zhiyong Huang
- Phone Number: 86-13995507729
- Email: Zyhuang126@126.com
-
Contact:
- Erlei Zhang
- Email: baiyu19861104@163.com
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Sampling Method
Non-Probability Sample
Study Population
Unresectable HCC patients with cirrhotic portal hypertension
Description
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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.
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
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.
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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%
|
6 weeks after first dose of Tislelizumab
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (OS)
Time Frame: through study completion, an average of 2 year
|
OS was defined as time from diagnosis to death from any cause or the last follow-up
|
through study completion, an average of 2 year
|
Progression Free Survival (PFS)
Time Frame: 18 months
|
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
|
18 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Zhiyong Huang, Tongji Hospital
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 15, 2024
Primary Completion (Estimated)
March 15, 2027
Study Completion (Estimated)
March 15, 2028
Study Registration Dates
First Submitted
February 20, 2024
First Submitted That Met QC Criteria
February 20, 2024
First Posted (Actual)
February 28, 2024
Study Record Updates
Last Update Posted (Actual)
April 10, 2024
Last Update Submitted That Met QC Criteria
April 9, 2024
Last Verified
April 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- uHCC-STI-TJ01
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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