Hepatocellular Carcinoma, Immunotherapy, Preoperative
Conditions
Brief summary
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 2 year event-free survival（2y-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 major pathological response, the rate of subjects with pathological complete response, event-free survival (EFS) and overall survival of camrelizumab combined with apatinib mesylate in the perioperative period of resectable hepatocellular carcinoma. The safety and tolerability is also evaluated.
Detailed description
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, adjuvant therapy (camrelizumab and apatinib, 6 cycles); in the control group, patients will be treated with following: radical surgery,adjuvant therapy (camrelizumab and apatinib, 6 cycles). The primary purpose of this study is to evaluate 2 year event-free survival（2y-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 major pathological response, the rate of subjects with pathological complete response, event-free survival (EFS) and overall survival of camrelizumab combined with apatinib mesylate in the perioperative period of resectable hepatocellular carcinoma. The safety and tolerability is also evaluated.
Interventions
DRUGCamrelizumab
Camrelizumab is administered at 200mg, q2w (2cycles) before radical surgery and 200mg, q3w (at least 6 cycles) after radical surgery
DRUGApatinib Mesylate
Apatinib Mesylate is administered at 250mg, qd (2 cycles) before radical surgery and 250mg, qd (at least 6 cycles) after radical surgery
PROCEDURERadical surgery
Radical surgery
PROCEDUREPreoperative TACE treatment
TACE treatment before preoperative camrelizumab combined with apatinib mesylate
Sponsors
Jiangsu Hengrui Pharmaceutical Co., Ltd.
The First Affiliated Hospital with Nanjing Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2 year event-free survival（2y-EFS） | 2-year | 2y-EFS is defined as time from randomization to any of the following events: progression of disease that precludes surgery, local or distant recurrence, or death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The rate of subjects of major pathological response (MPR) | 30-day | MPR is defined as less than 10% residual tumor after neoadjuvant therapy of camrelizumab and apatinib therapy. |
| Disease-free survival (DFS) | 3-year | DFS is defined as the time from randomization until disease recurrence or death from any cause. |
| the rate of subjects with pathological complete response (pCR) | 30-day | pCR is defined as no histologic evidence of malignancy or only the ingredients of carcinoma in situ was found in primary tumors. |
| Event-free survival (EFS) | 3-year | EFS is defined as the time from randomisation to tumor progression, postoperative relaspse or metastasis, or death, which occur first. |
| R0 resection rate | 30-day | R0 resection rate |
| Adverse event (AE) | 3-year | Adverse events (AEs) ; serious adverse events (SAEs); surgery related safety. |
| Overall survival (OS) | 3-year | OS is defined as the time from randomisation to death. |
Countries
China
Contacts
Primary ContactXuehao Wang, professor
Outcome results
None listed