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Hepatocellular CarcinomaPhase 2/3ALICENCT06904170

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

A Phase 2/3 study testing Durvalumab Plus Tremelimumab and HAIC (GEMOX) in people with Hepatocellular Carcinoma, run by UNICANCER at 11 sites in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
Durvalumab Plus Tremelimumab and HAIC (GEMOX)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
196 participants
Where
11 sitesFrance
Study dates
14 Nov 2025to Sep 2030
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • Performance status Eastern Cooperative Oncology Group (ECOG) 0 to 1
  • Must have a life expectancy of at least 12 weeks
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  • Body weight >30 kg
  • At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to randomization
  • Adequate organ and marrow function as indicated by the following laboratory values
  • Haemoglobin ≥ 7.5 g/dL. Participants with 7.5 g/dL < haemoglobin < 9.0 g/dL having active or chronic bleeding to be excluded,
  • Platelet count ≥75 × 109/L,
  • Absolute neutrophil count (ANC ≥1.0 × 109 /L)
  • creatinine clearance > 40 mL/min (according to Cockcroft or MDRD formula)
  • AST (SGOT)/ALT (SGPT) ≤5x ULN
  • Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN).
  • International normalised ratio (INR) < 2.3
  • Women of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥90 days after the last dose of study drug, and have a negative urine or serum pregnancy test ≤7 days of first dose of study drug. In case of a urine pregnancy test, it must be a highly sensitive urine pregnancy test.
  • Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥90 days after the last dose of study drug. A sterile male is defined as one for whom azoospermia has been previously demonstrated in a semen sample examination as definitive evidence of infertility. Males with known "low sperm counts" (consistent with "sub-fertility") are not to be considered sterile for purposes of this study.
  • Men and women patients must consent to not donate or bank sperm or ova during treatment and for 180 days after treatment stop
  • Patients must have provided consent for the study by signing and dating a written informed consent form prior to any study specific procedures, sampling, or analyses. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
  • Patient affiliated to a social security regimen

Who cannot join

  • 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).
  • Active or prior documented gastrointestinal bleeding (GI; eg, esophageal varices or ulcer bleeding) within the past 6 months. Note: For participants with a history of GI bleeding greater than 6 months or assessed as high risk for esophageal varices by the investigator, including main trunk portal vein thrombosis, a recent endoscopy within 3 months of enrolment and adequate endoscopic therapy according to institutional standards is required.
  • Any unresolved toxicity NCI CTCAE grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
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  • Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.
  • Any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician
  • Patients with celiac disease controlled by diet alone
  • History of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases
  • History of leptomeningeal carcinomatosis
  • Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV infection (defined as the presence of anti HBc and absence of HBsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Known to have been tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
  • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea
  • Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart)
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
  • Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of prednisone or its equivalent
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of study drug
  • History of allogenic organ transplantation, or patient with intent for transplantation
  • Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study drug. Note: Local surgery of isolated lesions for palliative intent is acceptable
  • Prior malignancy active within the previous 5 years of inclusion except for locally curable cancers considered cured or successfully resected, such as basal or squamous cell skin cancers, superficial bladder cancer, or gastric cancers, or carcinoma in situ of the prostate, cervix, or breast carcinomas. Any oncological concomitant treatment is not allowed during the treatment period.
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
  • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or180 days after the last dose of durvalumab and tremelimumab combination therapy.
  • Participation in another therapeutic trial within the 30 days prior to study inclusion
  • Prior randomisation or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.
  • Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
  • Patients deprived of their liberty or under protective custody or guardianship
  • Patients unable to adhere to the protocol for geographical, social, or psychological reasons or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent

Trial locations and contacts

11 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Veronica PEZZELLA contact

+33 6 28 69 53 14

v-pezzella@unicancer.fr

Guillaume BRARD contact

g-brard@unicancer.fr

11 sites in 1 country

France11 sites, 11 recruiting

  • CHU de Bordeaux

    Bordeaux, 33604

    Camille DUCERF, +33 5 57 62 34 47, camille.ducerf@chu-bordeaux.fr

    Jean-Frédéric BLANC, Professor

    Not yet recruiting

  • AP-HP Hôpital Beaujon

    Clichy, 92110

    Yasmine HEMDANE, +33 1 40 87 55 53, yasmine.hemdane@aphp.fr

    Mohamed BOUATTOUR, Doctor

    Recruiting

  • Centre Georges Francois Leclerc

    Dijon, 21079

    Sandrine TIAGO, +33 3 45 34 80 51

    Francois GHIRINGHELLI, Professor

    Not yet recruiting

  • Hôpital Saint Joseph

    Marseille

    Xavier Adhoute, +33 (0) 4 91 80 82 35, xadhoute@hopital-saint-joseph.fr

    Recruiting

  • CHU de Montpellier

    Montpellier, 34295

    Chloe GUILLOT, +33 4 67 33 73 27, chloe-guillot@chu-montpellier.fr

    Boris GUIU, Professor

    Not yet recruiting

  • CHU Hôtel-Dieu

    Nantes, 44093

    Claire PELUCHON, +33 2 53 48 22 43, claire.peluchon@chu-nantes.fr

    Yann TOUCHEFEU, Professor

    Not yet recruiting

  • AP-HP Hôpital Cochin

    Paris, 75014

    Emilie ROUSSEAUD, +33 1 58 41 29 88, emilie.rousseaud@aphp.fr

    Anais VALLET-PICHARD, Doctor

    Recruiting

  • CHU de Poitiers

    Poitiers, 86000

    Marielle DUBREUIL, +33 5 16 60 42 34, marielle.dubreuil@chu-poitiers.fr

    Amina LARBI, Doctor

    Not yet recruiting

  • Centre Eugene Marquis

    Rennes, 35042

    Enora MICHEL, +33 2 99 25 32 11, e.michel@rennes.unicancer.fr

    Julien EDELINE, Professor

    Recruiting

  • CHRU de Strasbourg

    Strasbourg, 67091

    Hakim TAYEBI, +33 3 88 11 51 58, Delegation_recherche@chru-strasbourg.fr

    Antonio SAVIANO, Doctor

    Not yet recruiting

  • CHU de Rangueil

    Toulouse, 31400

    Dehlia JURION, +33 5 61 32 30 71, jurion.d@chu-toulouse.fr

    Jean-Marie PERON, Professor

    Recruiting

Other trials in France

About this study

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

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.

Read more

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.

Read the 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.

Being tested
Durvalumab Plus Tremelimumab, HAIC (GEMOX)
Keywords
High tumor burden, HAIC, GEMOX, HCC,
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Durvalumab Plus TremelimumabDrug

    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 groups in NCT06904170
Study groupRoleWhat they receive
Arm AExperimentalDurvalumab + Tremelimumab (single dose), combined with Hepatic Arterial Infusion Chemotherapy (HAIC) of gemcitabine + oxaliplatin (GEMOX regimen)
Receives: Drug: Durvalumab Plus Tremelimumab; Drug: HAIC (GEMOX)
Arm BActive comparatorDurvalumab + Tremelimumab (single dose)
Receives: Drug: Durvalumab Plus Tremelimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 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

    Measured: From date of randomization to the date of death, up to 18 months after the randomization of the last patient

Secondary outcomes (6)

  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

    Measured: 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.

    Measured: 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.

    Measured: 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

    Measured: From date of randomization until the date of first documented progression, and up to 6 months after the inclusion of the last patient

  5. Health-Related Quality of Life (HRQoL) measured by the EORTC QLQ-C30 questionnaire

    Quality of life will be assessed with questionnaire EORTC QLQ-C30, at baseline and every 2 months until disease progression or study termination

    Measured: From date of randomization and until the date of first documented progression, up to 18 months after the inclusion of the last patient

  6. Health-Related Quality of Life (HRQoL) measured by the EORTC HCC-18 questionnaire

    Quality of life will be assessed with questionnaire EORTC HCC-18, at baseline and every 2 months until disease progression or study termination

    Measured: From date of randomization and until the date of first documented progression, up to 18 months after the inclusion of the last patient

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Apr 2025
  2. Study start14 Nov 2025
  3. Primary completion14 Sep 2029 (estimated)
  4. Study completionSep 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
196 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06904170
Sponsor's protocol ID
UC-GIG-2406
Other IDs
2024-514912-28-00
Acronym
ALICE
Status last verified
Jan 2026
First submitted
9 Mar 2025
Last updated
3 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Durvalumab Plus Tremelimumab and HAIC (GEMOX) in people with Hepatocellular Carcinoma, run by UNICANCER at 11 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 3 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Veronica PEZZELLA (+33 6 28 69 53 14, v-pezzella@unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06904170.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2026; AzTrials last refreshed its copy on 8 Nov 2026.

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