Effect of Splenectomy on Treatment for Unresectable Liver Cancer

Impact of Splenectomy on the Efficacy of Targeted Therapy and Immunotherapy in Unresectable HCC Patients With Cirrhotic Portal Hypertension

This study is testing if removing the spleen can help improve treatment outcomes for patients with advanced liver cancer who also have cirrhosis by using a combination of targeted therapy and immunotherapy.

Quick facts

• Study type: Observational
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Tongji Hospital (Academic / other)
• Drugs / interventions: chemotherapy, radiation, immunotherapy, Tislelizumab, Lenvatinib
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT06280313 on ClinicalTrials.gov

What this trial studies

This observational study investigates how splenectomy affects the efficacy of combined targeted therapy and immunotherapy in patients with unresectable hepatocellular carcinoma (HCC) who also have cirrhotic portal hypertension. Participants will undergo splenectomy followed by treatment with the PD-1 monoclonal antibody Tislelizumab and the targeted therapy Lenvatinib. The study aims to determine if splenectomy can improve treatment outcomes for these patients by enhancing liver function and immune response. The primary endpoint is disease progression or intolerable toxicity reactions.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with unresectable HCC, significant splenomegaly, and specific liver function criteria.

Not a fit: Patients with prior systemic antitumor treatment or those not meeting the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve treatment outcomes for patients with unresectable HCC and cirrhotic portal hypertension.

How similar studies have performed: While splenectomy has shown promise in improving liver function in cirrhotic patients, this specific combination of treatments is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Patients aged 18 to 75 years (inclusive).
2. No prior systemic antitumor treatment or meeting the criteria for splenectomy during treatment.
3. Clinical or pathological diagnosis of hepatocellular carcinoma (HCC) that is unresectable initially or has recurred after surgery.
4. HBV-DNA less than 1\*10\^5 copies/ml and undergoing antiviral therapy.
5. ECOG performance status score of 0-1, without significant organ dysfunction.
6. Child-Pugh score of 5-7.
7. Spleen thickness \>4.0 cm.
8. History of esophagogastric varices, red signs, or variceal bleeding with or without splenomegaly.
9. 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.
10. 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.
11. 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)).
12. Willing to provide informed consent.
13. Expected survival time of more than 3 months.

Exclusion Criteria:

1. 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).
2. Presence of central nervous system metastasis or a history of brain metastasis.
3. History of organ transplantation.
4. History of surgery in the head, chest, or abdomen within the past six months.
5. Child-Pugh class C liver function or significant ascites.
6. Marked thrombosis in the portal venous system or extensive cancer thrombus in the main portal vein.
7. 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.
8. Ongoing active infection within 7 days after completion of systemic antibiotic therapy.
9. Active coronary artery disease, severe/unstable angina, or newly diagnosed angina or myocardial infarction within the past 12 months before enrollment.
10. Thrombotic or embolic events within the past 12 months, such as cerebrovascular accidents (including transient ischemic attacks), pulmonary embolism, or deep vein thrombosis.
11. New York Heart Association (NYHA) class II or above congestive heart failure.
12. 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).
13. 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).
14. Interstitial lung disease, non-infectious pneumonia, or uncontrolled systemic diseases (e.g., diabetes, hypertension, pulmonary fibrosis, and acute pneumonia).
15. Pregnant or lactating women or females with a positive pregnancy test prior to the first dose who have the potential for pregnancy.
16. The investigator deems the subject inappropriate for participation in this clinical study due to any clinical or laboratory abnormalities or compliance issues.
17. Severe psychological or mental abnormalities.
18. Participation in another drug clinical trial within the past 4 weeks.
19. Other reasons that the investigator considers unsuitable for enrollment.

Where this trial is running

Wuhan, Hubei

• Tongji Hospital — Wuhan, Hubei, China (Recruiting)

Study contacts

• Principal investigator: Zhiyong Huang — Tongji Hospital
• Study coordinator: Zhiyong Huang

Conditions Unresectable Hepatocellular Carcinoma; Immunotherapy; Targeted therapy; Splenectomy; HCC