Hepatocellular carcinoma is one of the most intractable primary malignancies in the hepatobiliary and pancreatic tract with a poor overall survival worldwide. Unfortunately, the vast majority of hepatocellular carcinoma patients suffer from advanced unresectable or metastatic disease at diagnosis. Currently targeted therapy alone, or in combination with anti-vascular endothelial growth factor antagonist, is the standard first-line treatment for metastatic hepatocellular carcinoma. On the other hand, there is growing evidence suggesting that radiation therapy (external or internal) with or without immune checkpoint inhibitors can produce or even augment abscopal effect in which the tumours away from the radiation field also show significant tumour shrinkage. The underlying mechanism of eliciting abscopal effect includes the increased antigen presentation by the myeloid cells within the tumour stroma leading to enhanced tumour cell killing. Previous case reports showed that radiation therapy alone can induce abscopal effect in mice and human models. However, a robust and concrete evidence of abscopal effect with combinational immune checkpoint inhibitors and radioembolisation or external radiation therapy in hepatocellular carcinoma is still lacking. This study investigates the efficacy and safety of immune checkpoint inhibitors and radioembolisation as first-line treatment for previously untreated metastatic hepatocellular carcinoma.
Hepatocellular carcinoma is one of the most intractable primary malignancies in the hepatobiliary and pancreatic tract with a poor overall survival worldwide. Surgery in the form of hepatectomy or liver transplantation provides the best chance of cure for early-stage disease. Unfortunately, the vast majority of hepatocellular carcinoma patients suffer from advanced unresectable or metastatic disease at diagnosis. Currently targeted therapy alone, or in combination with anti-vascular endothelial growth factor antagonist, is the standard first-line treatment for metastatic hepatocellular carcinoma. On the other hand, there is growing evidence suggesting that radiation therapy (external or internal) with or without immune checkpoint inhibitors can produce or even augment abscopal effect in which the tumours away from the radiation field also show significant tumour shrinkage. The underlying mechanism of eliciting abscopal effect includes the increased antigen presentation by the myeloid cells within the tumour stroma leading to enhanced tumour cell killing. Previous case reports showed that radiation therapy alone can induce abscopal effect in mice and human models. However, a robust and concrete evidence of abscopal effect with combinational immune checkpoint inhibitors and radioembolisation or external radiation therapy in hepatocellular carcinoma is still lacking. This phase 2 single-arm study will investigate the efficacy and safety of combination of immune checkpoint inhibitors and radioembolisation for previously untreated metastatic hepatocellular carcinoma.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Durvalumab 1500mg intravenous infusion on week 1, 5, 9, 13, 17, 21 and 25 for a total of 7 cycles
Tremelimumab 300mg intravenous infusion on week 1 only.
Yttrium-90 radioembolisation on week 2 only.
Department of Clinical Oncology, Queen Mary Hospital
Hong Kong, Hong Kong
RECRUITINGBest objective response
Best objective response
Time frame: 3 years
Rate of abscopal effect
Rate of abscopal effect, which is defined as the rate of objective response of tumour sites outside the liver after radioembolisation and immune checkpoint inhibitor therapy
Time frame: 3 years
Progression-free survival
Progression-free survival
Time frame: 3 years
Overall survival
Overall survival
Time frame: 3 years
Incidence of treatment-related side effects
Incidence of treatment-related side effects as determined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time frame: 3 years
Local control rate
Local control rate, which is defined as the percentage of tumour sites in the liver without evidence of progressive disease after radioembolisation and immune checkpoint inhibitor therapy
Time frame: 3 years
Distant control rate
Distant control rate, which is defined as the percentage of tumour sites outside the liver without evidence of progressive disease after radioembolisation and immune checkpoint inhibitor therapy
Time frame: 3 years
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