Liver cancer is a highly lethal malignancy and has become increasingly important in western countries. The management of liver cancer is complex. In advanced disease, two combinations of immunotherapies are recommanded as first line (atezolizumab-bevacizumab or durvalumab-tremelimumab). Results in patients with high tumor burden (Portal vein thrombosis Vp3 or Vp4, or tumoral liver involvement \>50%) are less impressive. Innovative combinations are necessary to improve the outcome of patients.
Recently, control trials conducted in Asia highlighted the benefit of hepatic arterial infusion chemotherapy, especially in patients with high tumor burden. Studies including a limited number of patients shown that the combination seems feasible.
ALICE is a randomized multicentric Phase II/Phase III trial conducted in French medical centers, evaluating the efficacy and safety of durvalumab+tremelimumab with or without Hepatic Arterial Infusion Chemotherapy of the GEMOX regimen (gemcitabine + oxaliplatin), in patients with high tumor burden.
Oxaliplatin induce immunogenic cell death, and gemcitabin deplete regulatory immune cells. The GEMOX regimen thus has the potential for a synergic effect with immunotherapy in HCC.
The trial will provide an innovative treatment to patients with no alternative for locoregional treatment, and with limited results with actual systemic treatments. It will also be the first trial of Hepatic Arterial infusion for such patients in the western population.
Age ≥18 years old,
Patient presenting with hepatocellular carcinoma (HCC), diagnosed either by histological or radiological criteria as described by EASL criteria, if no biopsy could be performed safely.
High-tumor burden, defined as at least one of the three criteria: (i) Vp4 PVTT, (ii) Vp3 PVTT with bilobar tumoral involvement and/or (iii) liver involvement >50% (as assessed by the investigator). Extra-hepatic spread is allowed.
Child-Pugh A liver function
Previous systemic treatment (either immunotherapy, anti-angiogenics, chemotherapy, or any combination thereof)
Previous treatment with hepatic arterial infusion of chemotherapy
Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
History of hepatic encephalopathy within the past 6 months or requirement for medications to prevent or control encephalopathy (eg, no lactulose, rifaximin, etc if used for purposes of hepatic encephalopathy).
UNICANCER
Lead sponsor
AstraZeneca
Collaborator