Lenvatinib, Sintilimab Plus SIRT for Unresectable HCC

Official title

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

Overview

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

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).

Interventions

• Drug Lenvatinib, sintilimab plus SIRT
  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.

Primary outcome measures

• Progression free survival (PFS) according to mRECIST [Time frame: 2.5 years]

Secondary outcome measures (5)

• Progression free survival (PFS) according to RECIST 1.1 [Time frame: 2.5 years]
• Objective response rate (ORR) [Time frame: 2.5 years]
• Disease control rate (DCR) [Time frame: 2.5 years]
• Overall survival (OS) [Time frame: 2.5 years]
• Adverse Events (AEs) [Time frame: 2.5 years]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Second Affiliated Hospital of Guangzhou Medical University — Guangzhou

Identifiers

NCT: NCT05992584 · MIIR-14

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗