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

ConditionHepatocellular Carcinoma
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorUNICANCER

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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).

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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.

Treatment groups

196 Participants
are divided into 2 treatment groups
Group A: Arm AExperimental treatment 2 interventions
Group B: Arm BActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

Phase II : Objective Response Rate according to RECIST 1.1

The proportion of patients with Complete Response or Partial Response 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
2

Phase III : Overall Survival

The time between Randomisation and death from any cause

Time frame
From date of randomization to the date of death, up to 18 months after the randomization of the last patient

Secondary outcomes

1

Safety of the combination of immune therapy and HAIC

Will be assessed : * the frequency of limiting toxicities (LT) occuring during the combination phase (the first 12 weeks). LT are defined as any toxicity related to the experimental drug, that leads to definitive treatment discontinuation. * the frequency and severity of treatment-related adverse events as per NCI-CTCA v5.0

Time frame
From the first study treatment administration to 30 days after the last administration of study treatment
2

Progression-Free Survival

Defined as the delay between the date of randomization and the date of the first progression or death from any cause. Progression will be assessed via RECIST 1.1 and mRECIST.

Time frame
From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs first, up to 18 months after the inclusion of the last patient
3

Phase II : Overall Survival

Defined as the delay between randomization and death from any cause.

Time frame
From date of randomization to the date of death, up to 18 months after the randomization of the last patient
4

Phase III : Objective Response Rate

Defined as the proportion of patients with Complete Response or Partial Response 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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

UNICANCER

Lead sponsor

AstraZeneca

Collaborator

Source ClinicalTrials.gov
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