ALPPS Combined With Tislelizumab in Liver Malignancy

Phase 2

• Conditions: Liver Malignant Tumors
• Interventions: Procedure: ALPPS surgery; Drug: Tislelizumab

• Registration Number: NCT04996446
• Lead Sponsor: Fudan University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-08-01
• Status Verified: 2021-08
• Study First Submitted: 2021-08-04
• Study First Submitted QC: 2021-08-05
• Last Update Submitted: 2021-08-05
• Study First Posted: 2021-08-09
• Last Update Posted: 2021-08-09
• Primary Completion: 2023-08
• Study Completion: 2023-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Age ≥18 years and ≤70 years;

2. ECOG physical condition score: 0~1;

3. Clinical/pathological diagnosis of primary liver cancer or intrahepatic metastatic colorectal cancer;

4. Clinical evaluation requires (extended) hemihepatectomy;

5. Liver function Child A level

6. sFLR < 30%

7. 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);

8. Sign the informed consent voluntarily;

9. Good compliance, and family members willing to cooperate with follow-up.

Exclusion Criteria

1. Presence of extrahepatic organ/distant lymph node metastasis;
2. Hilar lymph node metastasis cannot be radically resected;
3. Patients with intrahepatic metastatic colorectal cancer had received second-line or above systemic therapy;
4. Other uncured malignant tumors;
5. Pregnant or lactating women who are pregnant during the study period need to withdraw from the clinical trial;
6. Concurrent use of any other antitumor therapy in patients with primary liver cancer;
7. Patients with intrahepatic metastatic colorectal cancer have been treated with antitumor therapy in addition to primary surgery and standard first-line/second-line therapy;
8. Patients with a known history of other systemic serious diseases before screening;
9. Long-term unhealed wounds or incomplete healing fractures;
10. Previous organ transplantation history;
11. Having a history of abuse of psychotropic substances and being unable to quit or having mental disorders;
12. A history of immune deficiency or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
13. Concomitant conditions that, in the investigator's judgment, seriously endanger the patient's safety or affect the patient's completion of the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Alpps group	ALPPS surgery	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.
Alpps plus Tislelizumab group	ALPPS surgery	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.
Alpps plus Tislelizumab group	Tislelizumab	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.

Primary Outcome Measures

Name	Time	Method
recurrence free survival	6 weeks	recurrence free survival

Secondary Outcome Measures

Name	Time	Method
safety (incidence of adverse events and serious adverse events)	3 weeks	incidence of adverse events and serious adverse events
overall survival	6 weeks	overall survival

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, China