NCT05809869

Immunotherapy and Radioembolisation for Metastatic Hepatocellular Carcinoma

A Phase 2 Study on Immune Checkpoint Inhibitors and Radioembolisation for Previously Untreated Metastatic Hepatocellular Carcinoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sponsor: The University of Hong Kong · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Hepatocellular Carcinoma

Interventions

Type	Name	Description
DRUG	Durvalumab	Durvalumab 1500mg intravenous infusion on week 1, 5, 9, 13, 17, 21 and 25 for a total of 7 cycles
DRUG	Tremelimumab	Tremelimumab 300mg intravenous infusion on week 1 only.
RADIATION	Yttrium-90 radioembolisation	Yttrium-90 radioembolisation on week 2 only.

Timeline

• Start date: 2023-02-15
• Primary completion: 2025-12-31
• Completion: 2026-06-30
• First posted: 2023-04-12
• Last updated: 2023-04-12

Locations

1 site across 1 country: Hong Kong