Tislelizumab or Tislelizumab Combined With Lenvatinib Neo-adjuvant Treatment for Resectable RHCC

Study Overview
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Brief Summary
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This non-randomized phase II clinical trial aimed to explore the efficacy and safety of Tislelizumab or Tislelizumab combined with Lenvatinib as neoadjuvant treatment for resectable RHCC patients

Detailed Description
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Hepatocellular carcinoma (HCC) patients have about 70% of 5-year recurrence rate after curative treatment. Only 30% of recurrent HCC (RHCC) patients are resectable when diagnosed. Neoadjuvant treatment may reduce tumor burden and recurrence rate after surgery for RHCC patients. Immune checkpoint inhibitors combined with or without antiangiogenic agents have already been reported effective in advanced HCC patients as first-line therapy, and in several early-stage solid tumors as neoadjuvant therapy. According to several preclinical results, immune infiltration and the expression of PD-1 were higher in RHCC tumors than in paired primary tumors. So, immune checkpoint inhibitors combined with or without antiangiogenic agents might have a better response in RHCC patients than primary HCC patients. Herein, we designed this phase II clinical trial to explore the efficacy and safety of Tislelizumab (PD-1 inhibitor) or Tislelizumab combined with Lenvatinib as neoadjuvant treatment for resectable RHCC patients. Enrolled resectable RHCC patients will be divided into two non-randomized seperate arms, sequentially (arm 1: neoadjuvant tislelizumab; arm 2: neoadjuvant tislelizumab and lenvatinib). Each arm was estimated to enroll 40 patients. We have already enrolled 11 patients in arm 1, and determined to terminate the enrollment of arm 1 due to modest treatment responses. The enrollment of arm 2 is ongoing.

Official Title
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Tislelizumab or Tislelizumab Combined With Lenvatinib Neo-adjuvant Treatment for Resectable Recurrent Hepatocellular Carcinoma：Phase II Non-randomized Control Clinical Trial

Conditions
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Recurrent Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Tislelizumab
* Drug: Tislelizumab combined with Levatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed as recurrent hepatocellular carcinoma after curative treatment; The criteria for resectability is met; Has at least one evaluable lesion according to the RECIST 1.1 standard and has not received local treatment; Eastern Cooperative Oncology Group score 0-1, Child-pugh score 5-7; Agree to biopsy and blood sample collection; Adequate organ and marrow function. Exclusion Criteria: Previously received any transarterial chemoembolization and immune therapy and other local or systemic liver cancer treatments, except for curative ablation; Extrahepatic metastasis; History of gastroesophageal varices or active cardia ulcers associated with a high risk of bleeding; History of autoimmune disease or need to take immunosuppressant drugs for a long time; History of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS); Abnormal organ function

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tislelizumab<br>Tislelizumab is one kind of PD-1 inhibitors. Patients enrolled will receive Tislelizumab as neoadjuvant treatment before surgery (200mg q3w*2 cycles) and as adjuvant treatment after surgery for 1 year | Drug: Tislelizumab<br>* Patients receive Tislelizumab on week 1 and week 4 (200mg, iv, q3w). After 2 cycles of Tislelizumab and evaluation of resectability, patients will receive surgery in 6 weeks after enrollment. Patients will receive Tislelizumab for 1 year (200mg, iv, q3w, 17 cycles) in 4-6 weeks after surgery.<br>|
| Experimental: Tislelizumab Combined Lenvatinib<br>Patients enrolled will receive Tislelizumab combined Lenvatinibas neoadjuvant treatment before surgery (Tislelizumab: 200mg q3w*2 cycles+Lenvatinib 8/12mg qd*4weeks) and as adjuvant treatment after surgery for 1 year | Drug: Tislelizumab combined with Levatinib<br>* Patients receive Tislelizumab on week 1 and week 4 (200mg, iv, q3w); Lenvatinib from Day1 to Day 28 (8/12mg qd). After neoadjuvant treatment and evaluation of resectability, patients will receive surgery in 6weeks after enrollment. Patients will receive Tislelizumab combined with Lenvatinib for 1 year in 4-6 weeks after surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival | Defined as the percent of patients without recurrence, progression or death in one year after enrollment | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | Defined as the percent of patients with a complete response (CR) or partial response (PR) documented by the Investigator per modified RECIST 1.1. | At time of surgery | 
| Incidence of severe adverse events | Defined as the percent of patients with adverse events over grade 3. | Three months after treatment | 
| Major pathological response rate | Defined as the percent of patients with less than 10% visible cancer cells out of the surface expression of the total tumor area at the time of surgery | At time of surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent hepatocellular carcinoma, neoadjuvant treatment, immune therapy