Camrelizumab Combined With Apatinib Mesylate and TACE in the Perioperative Treatment of 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 recurrence-free survival (RFS) 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 major pathological response, the rate of subjects with pathological complete response, event-free survival (EFS), overall survival and 12-months recurrence-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 ( perioperative TACE treatment，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 recurrence-free survival (RFS) 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 major pathological response, the rate of subjects with pathological complete response, event-free survival (EFS), overall survival and 12-months recurrence-free survival of camrelizumab combined with apatinib mesylate in the perioperative period of resectable hepatocellular carcinoma. The safety and tolerability is also evaluated.

Official Title
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Camrelizumab Combined With Apatinib Mesylate and TACE in the Perioperative Treatment of Hepatocellular Carcinoma: a Randomized, Open-label, Parallel, Multicenter Trial

Conditions
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Hepatocellular Carcinoma, Immunotherapy, Preoperative

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


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 years old, no gender limit. Hepatocellular carcinoma confirmed by histopathology, cytology or imaging. CNLC stage Ib (single tumor with diameter ≥8 cm)/IIa/IIb/IIIa hepatocellular carcinoma, except for CNLC IIIa hepatocellular carcinoma combined with main portal vein tumor thrombus；multiple hepatocellular carcinoma was allowed to be treated with surgical excision combined with intraoperative ablation. Child-Pugh score: A grade (≤6 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

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 TACE treatment → 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 at least 1 week after the last administration of neoadjuvant therapy, postoperative TACE treatment within 4 8 weeks after surgery, camrelizumab combined with apatinib mesylate at 1 week 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: Postoperative TACE treatment<br>* TACE treatment after radical surgery<br>Procedure: Radical surgery<br>* Radical surgery<br>Procedure: Preoperative TACE treatment<br>* TACE treatment before preoperative camrelizumab combined with apatinib mesylate<br>|
| Active Comparator: Radical surgery<br>Radical surgery→postoperative TACE treatment | Procedure: Postoperative TACE treatment<br>* TACE treatment after radical surgery<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 |
| --- | --- | --- |
| Recurrence-free survival (RFS) | RFS is defined as the time from the date of surgery to tumor postoperative relaspse or metastasis, or death, which occur first. | 3-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 resection rate | R0 resection rate | 30-day | 
| The rate of subjects of major pathological response (MPR) | MPR is defined as less than 10% residual tumor after neoadjuvant therapy of camrelizumab and apatinib therapy. | 30-day | 
| the rate of subjects with pathological complete response (pCR) | pCR is defined as no histologic evidence of malignancy or only the ingredients of carcinoma in situ was found in primary tumors. | 30-day | 
| Overall survival (OS) | OS is defined as the time from randomisation to death. | 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 | 
| 12 months recurrence free survival (12 months RFS) | 12 months RFS is defined as the rate of subjects with no recurrence-free in 12 months. | 12 months | 
| Safety and toleraty | The incidence of adverse evetns, severe adverse events; surgery related safety. | 3-year |