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

NCT06904170 | Recruiting Phase 2 DMC

• 2 other identifiers: UC-GIG-24062024-514912-28-00
• Study Type: interventional
• Target: 196
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Hepatocellular Carcinoma

Keywords

High tumor burden, HAIC, GEMOX, HCC,

Outcome Measures

Primary Outcomes (2)

• 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

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

• Phase III : Overall Survival

  The time between Randomisation and death from any cause

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

Secondary Outcomes (6)

• Safety of the combination of immune therapy and HAIC

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

• Progression-Free Survival

  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

• Phase II : Overall Survival

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

• Phase III : Objective Response Rate

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

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

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

Study Arms (2)

Arm A

EXPERIMENTAL

Durvalumab + Tremelimumab (single dose), combined with Hepatic Arterial Infusion Chemotherapy (HAIC) of gemcitabine + oxaliplatin (GEMOX regimen)

Drug: Durvalumab Plus Tremelimumab; Drug: HAIC (GEMOX)

Arm B

ACTIVE COMPARATOR

Durvalumab + Tremelimumab (single dose)

Drug: Durvalumab Plus Tremelimumab

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.

Arm A; Arm B

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.

Arm A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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).

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• UNICANCER: lead
• AstraZeneca: collaborator

Study Sites (11)

CHU de Bordeaux

Bordeaux, 33604, France

NOT YET RECRUITING

AP-HP Hôpital Beaujon

Clichy, 92110, France

RECRUITING

Centre Georges Francois Leclerc

Dijon, 21079, France

NOT YET RECRUITING

Hôpital Saint Joseph

Marseille, France

RECRUITING

CHU de Montpellier

Montpellier, 34295, France

NOT YET RECRUITING

CHU Hôtel-Dieu

Nantes, 44093, France

NOT YET RECRUITING

AP-HP Hôpital Cochin

Paris, 75014, France

RECRUITING

CHU de Poitiers

Poitiers, 86000, France

NOT YET RECRUITING

Centre Eugene Marquis

Rennes, 35042, France

RECRUITING

CHRU de Strasbourg

Strasbourg, 67091, France

NOT YET RECRUITING

CHU de Rangueil

Toulouse, 31400, France

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Julien EDELINE, Professor

  Centre Eugène Marquis

  PRINCIPAL INVESTIGATOR

• Laure Monard

  UNICANCER

  STUDY DIRECTOR

Central Study Contacts

Veronica PEZZELLA

CONTACT

+33 6 28 69 53 14; v-pezzella@unicancer.fr

Guillaume BRARD

CONTACT

g-brard@unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2025
• First Posted: April 1, 2025
• Study Start: November 14, 2025
• Primary Completion (Estimated): September 14, 2029
• Study Completion (Estimated): September 1, 2030
• Last Updated: February 3, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (11)