ALPPS Combined With Tislelizumab in Liver Malignancy

Fudan University

Status and phase: Unknown; Phase 2

Conditions: Liver Malignant Tumors

Treatments: Drug: Tislelizumab; Procedure: ALPPS surgery

Study type: Interventional

Funder types: Other

Identifiers

NCT04996446

2020-183-2103

Details and patient eligibility

About

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.

Enrollment: 20 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

Alpps plus Tislelizumab group

Experimental group

Description:

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.

Treatment:

Procedure: ALPPS surgery

Drug: Tislelizumab

Alpps group

Active Comparator group

Description:

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.

Treatment:

Procedure: ALPPS surgery