NCT07122089

Brief Summary

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, being the third leading cause of cancer-related death worldwide, with approximately 745 000 deaths reported annually. For advanced patients, including patients with tumoral portal vein thrombosis (PVT), most treatment guidelines recommend systemic therapy, either combination immunotherapy (IO) or combination of immunotherapy and anti-angiogenic treatment for first line option. Results for PVT patients are provided in one trial with a median overall survival of 14.2 months with IO underlying the necessity to improve treatment of PVT patients. Two recent other phase 3 trials also reported positive results for different IO regimen. Selective internal radiation therapy (SIRT) using yttrium-90 (90Y)-loaded glass microspheres (TheraSphereTM) can be used for patients with early stage to locally advanced HCC including PVT patients without extrahepatic spread (EHS). TheraSphereTM is recognized and is reimbursed in France for PVT patients without EHS, since 2019.Several retrospective studies have shown promising results for PVT patients. Nowadays use of SIRT in locally advanced HCC is regaining interest based on the results of the randomized DOSISPHERE-01 study including non-operable patients, about 70% with PVT. This randomized Phase II trial using 90Y-loaded microspheres sought was noted the effectiveness of 90Y-loaded microspheres using a personalized dosimetry approach versus a standard dosimetry approach. The use of a systemic treatment as IO after a locoregional treatment with the strong local debulking effect of SIRT is logical and of interest. Indeed, the most frequent pattern of progression after SIRT is recurrence in an untreated area, including untreated liver or EHS. Patients are then usually referred to IO. Such kind of therapeutic approach, using SIRT followed by IO has already been evaluated in a phase 2 study using nivolumab after 90Y loaded resin microspheres with promising efficacy without safety deterioration. The aim of this study is to evaluate SIRT followed by IO used according to their current indications in advanced HCC patient with PVT patients and without EHS.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
80

participants targeted

Target at P50-P75 for phase_2

Timeline
45mo left

Started Feb 2026

Typical duration for phase_2

Geographic Reach
1 country

6 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress5%
Feb 2026Jan 2030

First Submitted

Initial submission to the registry

August 7, 2025

Completed
7 days until next milestone

First Posted

Study publicly available on registry

August 14, 2025

Completed
7 months until next milestone

Study Start

First participant enrolled

February 25, 2026

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 2, 2030

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 2, 2030

Last Updated

May 5, 2026

Status Verified

August 1, 2025

Enrollment Period

3.9 years

First QC Date

August 7, 2025

Last Update Submit

April 29, 2026

Conditions

Hepatocellular Carcinoma Non-resectable

Keywords

Hepatocellular carcinomaImmunotherapySelective internal radiation therapy

Outcome Measures

Primary Outcomes (1)

  • Objective Response Rate (ORR)

    The Objective Response Rate (ORR) is defined as the proportion of patients who have either a Partial Response (PR) or a Complete Response (CR) to treatment. CR and PR are the best overall response across all time points of tumor evaluation. Overall tumor response at each time point is assessed according to the modified RECIST criteria for HCC.

    Through study completion, an average of 4 years

Study Arms (1)

Hepatocellular carcinoma with portal vein thrombosis and without hepatic spread

EXPERIMENTAL

Patient will receive selective internal radiation therapy and immunotherapy as per standard of care. SIRT Administration is direct intra-arterial injection in the hepatic artery to target only liver disease and IO will be performed as describe below: * Tremelimumab (Imjudo®): 300 mg IV, one-hour infusion; * Durvalumab (Imfinzi®): 1500 mg IV, one-hour infusion every 4 weeks.

Device: Selective Internal RadiotherapyDrug: TremelimumabDrug: Durvalumab

Interventions

Selective Internal RadiotherapyDEVICE

SIRT will use Yttrium-90 glass-microspheres (TheraSphereTM). SIRT needs two steps: the treatment simulation (diagnostic angiography and scintigraphy of hepatic perfusion with 99mTc-MAA) and the administration (during a therapeutic angiography).

Also known as: SIRT
Hepatocellular carcinoma with portal vein thrombosis and without hepatic spread
TremelimumabDRUG

Tremelimumab should be done 1 to 3 weeks after SIRT and is administrated according to the Summary of Product Characteristic (SPC).

Also known as: IMJUDO®
Hepatocellular carcinoma with portal vein thrombosis and without hepatic spread
DurvalumabDRUG

After the end of the tremelimumab infusion, patient receive durvalumab then one injection every 4 weeks until further progression upon investigator decision. Also administrated according to the Summary of Product Characteristic (SPC).

Also known as: Imfinzi®
Hepatocellular carcinoma with portal vein thrombosis and without hepatic spread

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥ 18,
  • ECOG Performance Status 0-1,
  • Histologically proven HCC or noninvasive HCC diagnosis according to LiRADS criteria,
  • HCC with Portal vein involvement (PVT), segmental, sectorial or lobar, evaluated by diagnostic imaging (CT scan or MRI),
  • At least one measurable lesion≥ 10mm using mRECIST criteria evaluated by diagnostic imaging,
  • Tumor involvement \<50% of the liver,
  • Hepatic reserve after SIRT ≥ 30% (i.e. hepatic parenchyma not treated with SIRT) evaluated by diagnostic imaging
  • No cirrhosis or Compensated cirrhosis (Child Pugh A, ALBI score 1 or 2),
  • SIRT indication confirmed by a multidisciplinary team meeting (i.e. patient not a candidate for liver resection, thermal ablation, or transplantation at the time of study),
  • Registration with a social security scheme,
  • Written and informed consent of the patient.

You may not qualify if:

  • Patient with main PVT (partial or complete),
  • Extrahepatic metastases (patients with EHS), except hilum node \< 2 cm,
  • Previous episode of ascites and/or presence of ascites, even if only seen on imaging without clinical detection (except minimum blade only peri-hepatic),
  • Pulmonary insufficiency (defined by an arterial oxygen pressure (PaO2) of \<60 mmHg, or oxygen saturation (SaO2) of \<90% (Roussos \& Koutsoukou, 2003) or clinically evident chronic obstructive pulmonary disease (COPD),
  • Medical history of radiation pneumonitis or recent pneumonitis, regardless of causality,
  • Previous HCC therapies:
  • Any prior systemic treatment for HCC;
  • More than 2 prior TACE (or embolization), in the area to be treated;
  • Liver resection or ablation \<6 months from end of previous treatment to TheraSphere administration;
  • Liver ablation \<3 months from end of previous treatment to TheraSphere administration.
  • Prior exposure to immune mediated therapy for HCC or other disease, such as other anti-PD-1, anti-PDL-1, anti-PDL-2, anti-CTLA-4, antibodies, etc.
  • Previous liver radiation (external beam radiation therapy (EBRT) or peptide receptor radionuclide therapy (PRRT) or SIRT
  • Inadequate hematological, hepatic and renal functions:
  • Hemoglobin \<8,5 g/dl;
  • Granulocytes \<1500/mm3;
  • +41 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

CHU de Grenoble

Grenoble, France

ACTIVE NOT RECRUITING

CHU de Lille

Lille, France

ACTIVE NOT RECRUITING

La Timone

Marseille, France

NOT YET RECRUITING

CHU de Montpellier

Montpellier, France

ACTIVE NOT RECRUITING

CHU de Nice

Nice, France

ACTIVE NOT RECRUITING

Centre Eugène Marquis

Rennes, France

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

tremelimumabdurvalumab

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Study Officials

  • Etienne Garin, MD PHD

    Centre de Lutte Contre Le cancer Eugène Marquis

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Tassadit AMROUN-SEBILLE

CONTACT

0299253137t.amroun-sebille@rennes.unicancer.fr

Valérie Jolaine

CONTACT

0299253036v.jolaine@rennes.unicancer.fr

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 7, 2025

First Posted

August 14, 2025

Study Start

February 25, 2026

Primary Completion (Estimated)

January 2, 2030

Study Completion (Estimated)

January 2, 2030

Last Updated

May 5, 2026

Record last verified: 2025-08

Locations

FR(6)