Phase III Randomized Clinical Trial of Radiotherapy Plus Toripalimab Versus Sorafenib in Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis
Overview
- Phase
- Phase 3
- Intervention
- Radiotherapy plus Toripalimab
- Conditions
- Radiotherapy
- Sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- TTP
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
To explore the efficacy of radiotherapy plus toripalimab Versus standard treatment of sorafenib in advanced hepatocellular carcinoma with Portal Vein/Hepatic vein Tumor Thrombosis.
Detailed Description
This is an single-center, open, randomized study, which is going to enroll patients filtered to meet the standard of advanced hepatocellular carcinoma, in a 2: 1-proportional randomly assigned to the test group and control group. Patients in the experimental group will be given local vein tumor thrombus/hepatic vein tumor thrombus +/- intrahepatic large lesions with hypofractionated intensity-modulated radiotherapy (tumor area dose 40-60Gy/10-20f), concurrent with and followed by 240mg Q3W of toripalimab within 1 week of radiotherapy started. Patients in the control group will be treated with sorafenib (400mg, twice a day).
Investigators
BO CHEN
Associate Professor
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Eligibility Criteria
Inclusion Criteria
- •Clinical or histologic diagnosis of Hepatocellular carcinoma (HCC) according to the 2019 version of liver cancer diagnosis and treatment guideline.
- •Aged between 18 and 80 years.
- •The left volume of liver-GTV which is received less than dose of 5Gy is more than 250ml after the portal vein/hepatic vein tumor thrombosis and its connected primary main lesion is received treatment dose of 40-60Gy/10-20f.
- •Patients may have a history of treatments for hepatocellular carcinoma such as TACE, radiofrequency, surgery, chemotherapy, and Chinese herbal medicine, but all patients must have not been received targeted therapy and Immunotherapy, such as anti-PD-1, anti-PD-L1 or anti-PD-L2 drug therapy.
- •BCLC Stage C, HCC combined with portal vein or hepatic vein tumor thrombosis. If it is a portal vein tumor thrombosis, it must involve the left or right portal trunk at least. If it is a hepatic vein tumor thrombosis, it must involve the left or middle or right main hepatic veins at least. At the same time, eligible patients have to meet one of the following conditions. (1) There are distant metastases (except for central nervous system and meningeal metastases); (2) Both hepatic lobes are showed multiple lesions which are unable to be fully covered within the target area; (3) portal vein tumor thrombosis involved main portal trunk.
- •The expected lifetime is more than 3 months.
- •Child A5, A6, B
- •Virus conditions: HBV DNA \<2000 IU/mL, if ≥ 2000 IU/mL, need to accept antiviral treatment until\<2000 IU/mL; patients with a positive HCV antibody must have a negative polymerase chain reaction (PCR) test result of HCV RNA;
- •Liver function: ALT is within 2.5 times of the upper limit of normal. AST can be within 6 times of the upper limit of normal if ALT is within 1.5 times of the upper limit of normal and cardiac infarction is excluded. If ALT is 1.5 to 2.5 times the upper limit of normal, AST must be within 1.5 times the upper limit of normal.
- •There is no obvious abnormality in the electrocardiography, and no obvious cardiac dysfunction.
Exclusion Criteria
- •Those who are participating in other clinical trials.
- •Had prior abdominal irradiation, or had prior liver transplantation.
- •Patients with chronic, serious diseases such as cardiac, pulmonary, and renal disease.
- •Suspected or true alcohol, drug abuse history.
- •May be allergic to treatment with sorafenib or toripalimab.
- •Have received immunotherapy in the past, such as anti-PD-1, anti-PD-L1, anti-PD-L2 drugs, and other drugs that stimulate or co-inhibitory T cell receptors (such as CTLA-4, OX- 40 or CD137) treatment
- •Severe mental or nervous system disorders that affect informed consent and/or expression or perception of adverse events.
- •Previous clinical diagnosis of hepatic encephalopathy in the past 6 months. Patients with hepatic encephalopathy which are controlled by rifaximin or lactulose are not allowed to participate in the study.
- •Moderate to severe ascitic fluid with obvious symptoms.
- •Concomitant secondary malignant tumors or other tumors (except superficial skin cancer, localized low-grade malignant tumors and carcinoma in situ) within 3 years before the start of the study.
Arms & Interventions
Radiotherapy plus Toripalimab
Patients in the experimental group will be given local vein tumor thrombus/hepatic vein tumor thrombus +/- intrahepatic large lesions with hypofractionated intensity modulated radiotherapy (tumor area dose 40-60Gy/10-20f), concurrent with and followed by 240mg Q3W of toripalimab within 1 week of radiotherapy.
Intervention: Radiotherapy plus Toripalimab
Sorafenib
Patients in the control group will be treated with sorafenib (400mg, twice a day).
Intervention: Sorafenib
Outcomes
Primary Outcomes
TTP
Time Frame: up to 24 months
Time to Progression (TTP) was defined as the duration from the date of patient recruited to the first progress at any site or the date of death.
Secondary Outcomes
- Incidence of grade 3 and above adverse events(up to 24 months)
- ORR(up to 24 months)
- OS(up to 24 months)