Liver Transplant Clinical Trial
— IMMUNO-THOfficial title:
Safety of Atezolizumab-Bevacizumab in Liver Transplanted Patients With Advanced Hepatocellular Carcinoma
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.
Status | Not yet recruiting |
Enrollment | 50 |
Est. completion date | December 15, 2028 |
Est. primary completion date | May 15, 2028 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 90 Years |
Eligibility | Inclusion Criteria: - All patients over 18 and under 90 years old: - 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 - With a proposal for Atezo-Beva in first line treatment made in a multidisciplinary meeting - ECOG Performance Status of 0 or 1 - For women of childbearing potential and men: agreement to remain abstinent - Child-Pugh class A Exclusion Criteria: - History of ACR within 3 months before starting Atezo-Beva treatment - Banff score for acute cellular rejection = 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 - Patient not having signed consent - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT-scan - History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death - Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding - A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment. - Inadequately controlled arterial hypertension - Prior history of hypertensive crisis or hypertensive encephalopathy - History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction including sub-occlusive disease related to the underlying disease or requirement for routine parenteral hydration - Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses |
Country | Name | City | State |
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n/a |
Lead Sponsor | Collaborator |
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Assistance Publique - Hôpitaux de Paris |
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | 6 months | |
Secondary | 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. | 24 months | |
Secondary | 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. | at the end of treatment | |
Secondary | 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. | between the inclusion and 24 months after the last inclusion | |
Secondary | Overall survival (OS) | The Overall survival (OS) defined by the time from inclusion to death from any cause | between the inclusion and 24 months after the last inclusion | |
Secondary | Objective Response Rate (ORR) | The Objective Response Rate (ORR) at 12 months is defined as the percentage of patients with a confirmed complete or partial response according to RECIST 1.1 criteria on imaging (CT-scan) performed every 3 months. | 12 months | |
Secondary | Duration of response | The Duration of response is defined by the time from first documentation of complete or partial response to disease progression or death according to RECIST 1.1 criteria on imaging (CT-scan) performed every 3 months. | between the inclusion and 24 months after the last inclusion | |
Secondary | Time to deterioration of quality of life | The time to deterioration of quality of life is defined as the time from inclusion to the first deterioration of quality of life as reported by the patient, with deterioration defined as a decrease from baseline of 10 points or more on the EORTC QLQ-C30 maintained for two consecutive assessments or a decrease of 10 points or more in one assessment followed by death from any cause within 3 weeks. Each quality of life evaluation will be reported by the patient using EORTC QLQ-C30 score fill formed every 6 months until 24 months after the initiation of the treatment. | between the inclusion and 24 months after the last inclusion | |
Secondary | Type, frequency and severity of adverse events and serious adverse events | They will be assessed on the basis of the nature, frequency and severity of adverse events according to NCI Common Terminology Criteria for Adverse Events, version 4.0. The management of side effects usually observed under immunotherapy will be managed according to the American Society of Clinical Oncology Clinical Practice Guidelines | between the inclusion, at the end of Atezo-Bev treatment and up to 24 months | |
Secondary | Donor Specific Antibodies (DSA) median | DSA will be assessed and correlation to ACR, the PFS and OS will be evaluated | baseline and at Day 21, 3 Months 6 Months , 12 Months , 18 Months , 24 Months |
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