Lenvatinib, Sintilimab Plus SIRT for Unresectable HCC

Sponsor

Second Affiliated Hospital of Guangzhou Medical University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05992584

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: Lenvatinib, sintilimab plus SIRT	Phase 2

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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Aug 10, 2023

Anticipated Primary Completion Date :

Jan 9, 2026

Anticipated Study Completion Date :

Aug 9, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Len-Sin-SIRT Lenvatinib, sintilimab plus SIRT	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.

Arm

Intervention/Treatment

Experimental: Len-Sin-SIRT

Lenvatinib, sintilimab plus SIRT

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.

Outcome Measures

Primary Outcome Measures

Progression free survival (PFS) according to mRECIST [2.5 years]
The time from initiation of treatment until the first occurrence of disease progression or death from any cause, whichever occurs first.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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