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

Sponsor
UNICANCER
Study ID
NCT06904170
Phase
PHASE2/PHASE3
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Durvalumab Plus Tremelimumab — DRUG
    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.
  • HAIC (GEMOX) — DRUG
    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.

Study Details

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.

Key Dates

Start date
Nov 14, 2025
Status verified
Jan 2026
Primary completion
Sep 14, 2029
Completion
Sep 30, 2030

Study Design

Enrollment
196 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Arm A
    Durvalumab + Tremelimumab (single dose), combined with Hepatic Arterial Infusion Chemotherapy (HAIC) of gemcitabine + oxaliplatin (GEMOX regimen)
  • Active Comparator: Arm B
    Durvalumab + Tremelimumab (single dose)

Primary Outcome Measure

Phase II : Objective Response Rate according to RECIST 1.1 [ Time Frame: From date of randomization until the date of first documented progression, and up to 6 months after the inclusion of the last patient ]

Central Contacts

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