Lenvatinib, Sintilimab Plus SIRT for Unresectable HCC

Study Overview
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Brief Summary
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This study is conducted to evaluate the efficacy and safety of lenvatinib, sintilimab plus Y-90 selective internal radiation therapy (SIRT) for patients with unresectable intermediate-advanced hepatocellular carcinoma (HCC).

Detailed Description
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This is a single-center, prospective study to evaluate the efficacy and safety of lenvatinib, sintilimab plus SIRT (Len-Sin-SIRT) in patient with unresectable HCC. 30 patients with unresectable intermediate-advanced HCC (BCLC B/C stage) will be enrolled in this study. The patients will receive lenvatinib (body weight ≥60kg, 12mg; body weight <60kg, 8mg; P.O. QD) and sintilimab (200mg I.V. Q3W) at 3-7 days after SIRT. Sintilimab will last up to 24 months, or until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. Lenvatinib will last until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. The primary end point of this study is Progression free survival (PFS) per mRECIST. The secondary endpoints are PFS per RECIST 1.1, objective response rate (ORR), disease control rate (DCR), overall survival (OS) and adverse events (AEs).

Official Title
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Lenvatinib, Sintilimab Plus Y-90 Selective Internal Radiation Therapy for Patients With Unresectable Intermediate-advanced Hepatocellular Carcinoma: a Prospective, Single-center, Single Arm Trial

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Lenvatinib, sintilimab plus SIRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unresectable HCC (BCLC stage B/C) with diagnosis confirmed by histology/cytology or clinically At least one measurable untreated lesion Intrahepatic tumors can be treated with 1-2 session of SIRT Child-Pugh score 5-7 Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 Life expectancy of at least 3 months Patients with active hepatitis B are allowed, but they need to receive antiviral treatment to achieve a HBV DNA<10^3 IU/mL Patients with hepatitis C need to finish the anti-HCV treatment Exclusion Criteria: tumor extent ≥70% liver occupation Tumor thrombus involving main portal vein or both the first left and right branch of portal vein Vena cava invasion Central nervous system metastasis Metastatic disease that involves major airways or blood vessels Patients who previously received hepatic arterial infusion chemotherapy (HAIC), transarterial chemoembolization (TACE), transarterial embolization (TAE), radiotherapy, systemic therapy, or immunotherapy for HCC History of organ and cell transplantation Prior esophageal and/or gastric varices bleeding History of hepatic encephalopathy Peripheral blood white blood cell count<3×10^9/L, platelet count<50×10^9/L Prolongation of prothrombin time ≥ 4 seconds Severe organ dysfunction (heart, lungs, kidneys) History of malignancy other than HCC HBsAg and anti-HCV antibody positive concurrently Human immunodeficiency virus (HIV) infected

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Len-Sin-SIRT<br>Lenvatinib, sintilimab plus SIRT | Drug: Lenvatinib, sintilimab plus SIRT<br>* Lenvatinib 12mg (body weight ≥60kg) or 8mg (body weight <60kg) P.O. QD and sintilimab 200mg I.V. q3w will be started at 3-7 days after the first SIRT. Treatment of sintilimab will last up to 24 months. Patients will be allowed to have lenvatilib or sintilimab as a sigle agent and will be still considered on study when the other drug cause intolerable toxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) according to mRECIST | The time from initiation of treatment until the first occurrence of disease progression or death from any cause, whichever occurs first. | 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) according to RECIST 1.1 | The time from initiation of treatment until the first occurrence of disease progression or death from any cause, whichever occurs first. | 2.5 years | 
| Objective response rate (ORR) | The percentage of patients who had a best overall tumor response rating of complete response (CR) or partial response (PR) according to mRECIST and RECIST 1.1 | 2.5 years | 
| Disease control rate (DCR) | The percentage of patients who had a tumor response rating of CR, PR, or stable disease (SD) according to mRECIST and RECIST 1.1 | 2.5 years | 
| Overall survival (OS) | The time from initiation of treatment until the date of death from any cause. | 2.5 years | 
| Adverse Events (AEs) | Number of patients with AEs assessed by NCI CTCAE v5.0. | 2.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular Carcinoma, Lenvatinib, Sintilimab, Yttrium-90