NCT06904170

Durvalumab and Tremelimumab With or Without Hepatic Arterial Infusion of Chemotherapy in Hepatocellular Carcinoma

An Integrated Phase II/III Randomized Study Comparing Durvalumab and Tremelimumab +/- Hepatic ArteriaL Infusion Chemotherapy With GEMOX in Hepatocellular Carcinoma With High Tumor burdEn

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 196 (estimated)
• Sponsor: UNICANCER · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

The ALICE study will randomize 196 patients in about 20 sites in France, according to a ratio 1:1, and in 2 steps : * 90 Patients will first be included in the initial Phase II study, and compared in terms of ORR. * 106 additional patients with be included for the Phase III, and the total population will be analyzed in terms of Overall Survival. A safety run-in phase will be planned for the first 12 patients in the experimental arm, to assess the tolerance of the treatment combination. An independent Study Monitoring Board (DSMB), with expertise and experience in the pathology, and without direct involvement in the conduct of the study, will be set up specifically to ensure optimal safety monitoring.

Conditions

• Hepatocellular Carcinoma

Interventions

Type	Name	Description
DRUG	Durvalumab Plus Tremelimumab	Systemic infusion of : Tremelimumab 300 mg, single dose at Cycle 1 Durvalumab 1500 mg at Cycle 1 then every 4 weeks until disease progression or unacceptable toxicity. Durvalumab and Tremelimumab will be delivered during a single angiography. Implantable catheter is also allowed. Durvalumab infusion will start 1 hour after the end of the tremelimumab infusion.
DRUG	HAIC (GEMOX)	Hepatic Arterial Infusion of Chemotherapy (HAIC) : Gemcitabine 1000 mg/m² over 30 minutes, followed by Oxaliplatin 100 mg/m² over 2 hours. Administered every 2 weeks for 4 cycles. When a Durvalumab cycle match with an HAIC infusion, HAIC will be delivered on the same day.

Timeline

• Start date: 2025-11-14
• Primary completion: 2029-09-14
• Completion: 2030-09-01
• First posted: 2025-04-01
• Last updated: 2026-02-03

Locations

11 sites across 1 country: France