Camrelizumab Combined With Apatinib Mesylate for Perioperative Treatment of Resectable Hepatocellular Carcinoma

Study Overview
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Brief Summary
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Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Hepatectomy is a curable and effective method. However, the recurrence rate is as high as 50% 70% in 5 years after surgery. Perioperative treatment with immunotherapy combined with target therapy is expected to improve the patient's prognosis. This study aims to evaluate the efficacy, safety and tolerability of camrelizumab combined with apatinib mesylate in the perioperative period of resectable hepatocellular carcinoma. The primary purpose of this study is to evaluate the rate of subjects with major pathological response and 3-year event-free survival (EFS) of camrelizumab combined with apatinib mesylate in the perioperative period of hepatocellular carcinoma (CNLC Ib-IIIa). The secondary research purpose is to evaluate the R0 resection rate, the rate of subjects with pathological complete response, EFS, overall survival and disease-free survival of camrelizumab combined with apatinib mesylate in the perioperative period of resectable hepatocellular carcinoma. The safety and tolerability is also evaluated.

Detailed Description
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Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Hepatectomy is a curable and effective method. However, the recurrence rate is as high as 50% 70% in 5 years after surgery. Perioperative treatment with immunotherapy combined with target therapy is expected to improve the patient's prognosis. This study aims to evaluate the efficacy, safety and tolerability of camrelizumab combined with apatinib mesylate in the perioperative period of resectable hepatocellular carcinoma. This trial includes subjects with CNLC Ib/IIa/IIb/IIIa HCC. All eligible subjects will be randomized (1:1) to experimental group or control group. In the experimental group, patients will be treated with following: neoadjuvant therapy (camrelizumab and apatinib, 2 cycles), radical surgery, postoperative TACE treatment, adjuvant therapy (camrelizumab and apatinib, 6 cycles); in the control group, patients will be treated with following: radical surgery, postoperative TACE treatment. The primary purpose of this study is to evaluate the rate of subjects with major pathological response and 3-year event-free survival (EFS) of camrelizumab combined with apatinib mesylate in the perioperative period of HCC. The secondary research purpose is to evaluate the R0 resection rate, the rate of subjects with pathological complete response, EFS, overall survival and disease-free survival of camrelizumab combined with apatinib mesylate in the perioperative period of resectable HCC. The safety and tolerability is also evaluated.

Official Title
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Camrelizumab Combined With Apatinib Mesylate for Perioperative Treatment of Resectable Hepatocellular Carcinoma：a Randomized, Open-label, Parallel, Multicenter Trial

Conditions
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Hepatocellular Carcinoma, Immunotherapy, Molecular Targeted Therapy

Intervention / Treatment
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* Drug: Camrelizumab
* Drug: Apatinib Mesylate
* Procedure: TACE treatment
* Procedure: Radical surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Volunteer to participate in this study and sign an informed consent form Age 18 75 years old, no gender limit Hepatocellular carcinoma confirmed by histopathology, cytology or imaging CNLC stage Ib/IIa/IIb/IIIa hepatocellular carcinoma, except for CNLC IIIa hepatocellular carcinoma combined with main portal vein tumor thrombus Child-Pugh score: A-B grade (≤7 points) ECOG PS score: 0-1 points Exclusion Criteria: Known intrahepatic cholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and fibrolamellar cell carcinoma; have other active malignancies other than HCC within 5 years or at the same time. Currently accompanied by interstitial pneumonia or interstitial lung disease Existence of active autoimmune disease or history of autoimmune disease and may relapse Patients with active infection, unexplained fever ≥38.5℃ within 1 week before randomization, or baseline white blood cell count >15*10^9/L Patients with congenital or acquired immune deficiencies (such as HIV-infected persons) Those who are known to be allergic to any monoclonal antibodies, anti-angiogenesis targeted drugs or excipients

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>Preoperative camrelizumab combined with apatinib mesylate (q2w, 2 cycles) → radical surgery → postoperative TACE treatment → sequential camrelizumab and apatinib mesylate (q3w, at least 6 cycles) (Note: Surgery within 2-4 weeks after the last administration of neoadjuvant therapy, postoperative TACE treatment at least 4 weeks after surgery, and camrelizumab combined with apatinib mesylate within 2 weeks after TACE treatment) | Drug: Camrelizumab<br>* Camrelizumab is administered at 200mg, q2w (2cycles) before radical surgery and 200mg, q3w (at least 6 cycles) after radical surgery<br>Drug: Apatinib Mesylate<br>* Apatinib Mesylate is administered at 250mg, qd (2 cycles) before radical surgery and 250mg, qd (at least 6 cycles) after radical surgery<br>Procedure: TACE treatment<br>* TACE treatment<br>Procedure: Radical surgery<br>* Radical surgery<br>|
| Active Comparator: Control group<br>Radical surgery→postoperative TACE treatment | Procedure: TACE treatment<br>* TACE treatment<br>Procedure: Radical surgery<br>* Radical surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year event-free survival (EFS) | EFS is defined as the time from randomisation to tumor progression, postoperative relaspse or metastasis, or death, which occur first. | 3-year | 
| The rate of subjects of major pathological response (MPR) | MPR is defined as less than 50% residual tumor after neoadjuvant therapy of camrelizumab and apatinib therapy. | 30-day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | OS is defined as the time from randomisation to death. | 3-year | 
| Disease-free survival (DFS) | DFS is defined as the time from surgery to postoperative relaspse or metastasis, or death, which occur first. | 3-year | 
| Event-free survival (EFS) | EFS is defined as the time from randomisation to tumor progression, postoperative relaspse or metastasis, or death, which occur first. | 3-year | 
| R0 resection rate | R0 resection rate | 30-day | 
| Safety and toleraty | The incidence of adverse evetns, severe adverse events; surgery related safety. | 30-day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Camrelizumab; apatinib mesylate; hepatocellular carcinoma