The purpose of this study is to assess the efficacy and safety of Apatinib Mesylate combined with PD-1 antibody SHR-1210 in HCC patients with high risk of disease recurrence contained microsatellite lesions, microvascular invasion(MVI) or secondary and above portal vein tumor thrombosis (PVTT) after radical resection. Patients will be randomized 1:1 either to the experimental arm to receive Apatinib Mesylate and PD-1 antibody SHR-1210 or to the standard therapy arm of hepatic arterial infusion(HAI) .
Hepatocellular carcinoma (HCC) is a common malignancy worldwide, which is the third cause of cancer related deaths. Radical hepatic resection is one of the most potentially curative treatments for HCC. Unfortunately, the long-term survival after radical hepatic resection is unsatisfactory because of the high incidence of tumor recurrence with the recurrence rates at 2 and 5 years are approximately 50 % to 60 % and 80 %,respectively. Microsatellite lesions, microvascular invasion (MVI) , or portal vein tumor thrombosis (PVTT) are the main risk factors for poor prognosis in HCC. HCC is a typical vascular-rich tumor, and its occurrence, development, metastasis and invasion are closely related to angiogenesis. Due to the long-term chronic inflammatory response of the liver, the establishment and development of HCC can be induced by creating an immunosuppressive microenvironment, including up-regulation of PD-1 receptors. Therefore, immunotherapy is also considered to be a potential effective method for advanced HCC treatment. And there is little convincing evidence indicating that adjuvant therapy reduces the risk of recurrence after hepatic resection. Furthermore, no standard regimen has been established. In the present study, we assessed the efficacy and safety of Apatinib Mesylate that is Small molecule anti-angiogenic targeted drugs /PD-1 antibody SHR-1210 combination therapy for surgically resected HCCs with high incidence of tumor recurrence containing microsatellite lesions, microvascular invasion(MVI) or secondary and above portal vein tumor thrombosis (PVTT).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
200
Apatinib mesylate tablets: 250 mg, orally once a day. Take about half an hour after a meal with warm water (the daily dose should be as much as possible. SHR-1210: 200mg, intravenous infusion for 30 minutes (including the time of the tube, the overall infusion time is not shorter than 20 minutes, no longer than 60 minutes), once every 2 weeks. A total of 6 months of treatment,starting 4-8 weeks after radical hepatic resection.
Twice standard HAI treatment, the first treatment was performed 4-8 weeks after radical hepatic resection, and the second treatment was given 4-8 weeks after the first treatment (the specific time interval depends on the recovery of liver function of the patient). The specific dosage regimen is 80-100 mg of epirubicin or 50 mg of epirubicin + oxaliplatin 50 mg per HAI treatment.
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, China
Recurrence-free survival(RFS)
Duration from surgery to tumor recurrence or death for any reason will be recorded to assess the clinical efficacy of Apatinib Mesylate plus PD-1 antibody SHR-1210 for HCC with high incidence of tumor recurrence after radical resection
Time frame: 72 month
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