Safety of Atezolizumab-Bevacizumab in Liver Transplanted Patients With Advanced Hepatocellular Carcinoma

Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-90
SponsorAssistance Publique - Hôpitaux de Paris

About this trial

The prognosis of liver transplanted (LT) patients with recurrence of hepatocellular carcinoma (HCC), especially those with progression after locoregional treatment or advanced HCC, remains poor. Current treatment modalities involve tyrosine kinase inhibitors (TKIs) characterized by a low response rate and often poor tolerability. Encouraging findings from the Imbrave 150 study, demonstrating increased survival rates coupled with favorable treatment tolerance, prompt the investigators to consider the potential of offering the combination of treatment with Atezolizumab-Bevacizumab (Atezo-Beva) to patients with LT. No data regarding the safety and efficacy of this new combination are available for patients with LT as they were not included in Imbrave 150. Immunosuppression after LT is low when compared to essentially all other organ recipients, liver recipients are considered with lower immunological risk. However, the use of ICIs has been associated with a risk of hepatic rejection in LT patients. In this study, in order to prevent acute cellular rejection (ACR) occurrence, we propose to adopt a standardized immunosuppressive regimen closed to the one used immediately after LT but with lower therapeutic goals for tacrolimus and everolimus to allow immunotherapy treatment to be effective. The better tolerance of liver grafts will probably lead to less risk of rejection with Atezo-Beva than in other organ transplants.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

who underwent LT more than 6 months ago (to prevent the higher risk of ACR which exists within the first months after LT and to deal with populations with a lowered immunosuppressive regimen long after LT)

with HCC recurrence diagnosis according to the EASL diagnostic criteria (33)

with advanced HCC not accessible to surgery and locoregional treatment

with at least one measurable untreated lesion

Disqualifiers

History of ACR within 3 months before starting Atezo-Beva treatment

Banff score for ACR ≥ 3 on liver biopsy performed before the initiation of the treatment

Pregnant or breastfeeding woman

Patient not affiliated to a beneficiary or entitled social security scheme or to the PUMA

Trial design

Design model

Single group

Treatments tested in this trial

  • Systemic therapy

    Drug

    Atezolizumab-Bevacizumab every 3 weeks until progression or side effects in combination with Standardized immunosuppressive treatment: Tacrolimus (objective 5-7 ng/ml) Mycophenolate Mofetil 1000 mg per day Corticosteroids at least 5 mg per day Everolimus will be continued if already started before the inclusion (objective 5-7 ng/ml). If everolimus has not been started prior to inclusion, do not start it, but adopt the following protocol: corticoids + Tacrolimus + Cellcept.

Treatment groups

50 Participants
are divided into 1 treatment group
Group A: Atezo-Beva combinationExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Rate of Acute cellular rejection (ACR) (defined by a Histological Banff score ≥ 5) at 6 months (confirmed by an external expert center)

To study the safety (ACR on histology) at 6 months of the first-line Atezo-Beva combination in LT patients with recurrent HCC in association with a standardized immunosuppressive treatment to prevent the risk of liver graft rejection

Time frame
6 months

Secondary outcomes

1

Rate of Acute Cellular Rejection (ACR) at 24 months

Rate of ACR (defined by a Histological Banff score ≥ 5) at 24 months (confirmed by a second external expert center.

Time frame
24 months
2

Rate of Acute Cellular Rejection (ACR) at the end of Atezo-Beva treatment

Rate of ACR (defined by a Histological Banff score ≥ 5) at 24 months and at the end of Atezo-Beva treatment (confirmed by a second external expert center.

Time frame
at the end of treatment
3

Progression Free Survival (PFS)

The Progression Free Survival (PFS) is defined as the time from inclusion to disease progression according to RECIST 1.1 on imaging (CT-scan) performed every 3 months or death from any cause, whichever occurred first.

Time frame
between the inclusion and 24 months after the last inclusion
4

Overall survival (OS)

The Overall survival (OS) defined by the time from inclusion to death from any cause

Time frame
between the inclusion and 24 months after the last inclusion

Other outcomes

Sponsors and contacts

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