ALPPS Combined With Tislelizumab in Liver Malignancy

Study Overview
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Brief Summary
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Study design: Prospective, single-center, phase IIa clinical trial; Primary endpoint: Recurrence free survival; Secondary endpoints: Safety, overall survival; Main characteristics of patients: Liver malignancy, required (extended) hemihepatectomy, insufficient liver reserve; Study approaches: The experimental group is treated with ALPPS combined with Tislelizumab, and the control group was treated with ALPPS; Sample size: 20 (10:10); Study process: In experimental group, patients who meet the inclusion criteria will receive ALPPS stage I surgery, treated with Tislelizumab 2-4 weeks after stage I surgery, and receive ALPPS stage II surgery 2-4 weeks after Tislelizumab treatment, and treated with Tislelizumab q3W 6-12 months after stage II surgery; In control group, patients who meet the inclusion criteria will receive ALPPS stage I surgery, and receive ALPPS stage II surgery 3-6 weeks after stage I surgery.

Official Title
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Safety and Efficacy of the Combinationg of Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) and Tislelizumab in Liver Malignancy

Conditions
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Liver Malignant Tumors

Intervention / Treatment
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* Drug: Tislelizumab
* Procedure: ALPPS surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years and ≤70 years; ECOG physical condition score: 0 1; Clinical/pathological diagnosis of primary liver cancer or intrahepatic metastatic colorectal cancer; Clinical evaluation requires (extended) hemihepatectomy; Liver function Child A level sFLR < 30% The main organs function well, and the examination indicators meet the following requirements: Routine blood tests: Hemoglobin ≥90 g/L (no blood transfusion within 14 days); Neutrophil count ≥1.5×10^9/L; Platelet count ≥80×10^9/L; Biochemical examination: Total bilirubin ≤2×ULN (upper normal value); ALT or AST ≤ 2.5×ULN; Endogenous creatinine clearance ≥ 50 mL /min (Cockcroft-Gault formula); Sign the informed consent voluntarily; Good compliance, and family members willing to cooperate with follow-up. Exclusion Criteria: Presence of extrahepatic organ/distant lymph node metastasis; Hilar lymph node metastasis cannot be radically resected; Patients with intrahepatic metastatic colorectal cancer had received second-line or above systemic therapy; Other uncured malignant tumors; Pregnant or lactating women who are pregnant during the study period need to withdraw from the clinical trial; Concurrent use of any other antitumor therapy in patients with primary liver cancer; Patients with intrahepatic metastatic colorectal cancer have been treated with antitumor therapy in addition to primary surgery and standard first-line/second-line therapy; Patients with a known history of other systemic serious diseases before screening; Long-term unhealed wounds or incomplete healing fractures; Previous organ transplantation history; Having a history of abuse of psychotropic substances and being unable to quit or having mental disorders; A history of immune deficiency or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; Concomitant conditions that, in the investigator's judgment, seriously endanger the patient's safety or affect the patient's completion of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alpps plus Tislelizumab group<br>Patients who meet the inclusion criteria will receive ALPPS stage I surgery, treated with Tislelizumab 2-4 weeks after stage I surgery, and receive ALPPS stage II surgery 2-4 weeks after Tislelizumab treatment, and treated with Tislelizumab q3W 6-12 months after stage II surgery. | Drug: Tislelizumab<br>* In experimental group, patients who meet the inclusion criteria will receive ALPPS stage I surgery, treated with Tislelizumab 2-4 weeks after stage I surgery, and receive ALPPS stage II surgery 2-4 weeks after Tislelizumab treatment, and treated with Tislelizumab q3W 6-12 months after stage II surgery.<br>Procedure: ALPPS surgery<br>* In experimental group, patients who meet the inclusion criteria will receive ALPPS stage I surgery, and receive ALPPS stage II surgery 4-8 weeks after stage I surgery; In control group, patients who meet the inclusion criteria will receive ALPPS stage I surgery, and receive ALPPS stage II surgery 3-6 weeks after stage I surgery.<br>|
| Active Comparator: Alpps group<br>Patients who meet the inclusion criteria will receive ALPPS stage I surgery, and receive ALPPS stage II surgery 3-6 weeks after stage I surgery. | Procedure: ALPPS surgery<br>* In experimental group, patients who meet the inclusion criteria will receive ALPPS stage I surgery, and receive ALPPS stage II surgery 4-8 weeks after stage I surgery; In control group, patients who meet the inclusion criteria will receive ALPPS stage I surgery, and receive ALPPS stage II surgery 3-6 weeks after stage I surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| recurrence free survival | recurrence free survival | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety (incidence of adverse events and serious adverse events) | incidence of adverse events and serious adverse events | 3 weeks | 
| overall survival | overall survival | 6 weeks |