bTAE-HAIC Combined With Lenvatinib and Sintilimab for Infiltrative Hepatocellular Carcinoma

Study Overview
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Brief Summary
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This study intends to evaluate the efficacy and safety of blank- microsphere transcatheter arterial embolization-hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin (bTAE-HAIC) plus Lenvatinib and Camrelizumab for patients with infiltrative hepatocellular carcinoma.

Detailed Description
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Blank-microsphere transcatheter arterial embolization (bTAE) and hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, 5-fluorouracil and leucovorin are effective and safe for hepatocellular carcinoma. Lenvatinib is non-inferior to sorafenib in overall survival in untreated advanced hepatocellular carcinoma. Sintilimab, a programmed cell death protein-1 (PD-1) inhibitor, is effective and safe in patients with unresectable hepatocellular carcinoma. No study has evaluated bTAE-HAIC plus Lenvatinib and Sintilimab. Thus, the investigators carried out this prospective, single-arm study to find out it.

Official Title
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Sequential bTAE-HAIC Combined With Lenvatinib and Sintilimab for Infiltrative Hepatocellular Carcinoma

Conditions
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Liver Diseases, Hepatocellular Carcinoma, Immunotherapy, Lenvatinib, Sintilimab

Intervention / Treatment
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* Procedure: bTAE-HAIC
* Drug: Lenvatinib
* Drug: Sintilimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of infiltrative HCC. Infiltrative HCC was characterized as follows: nonencapsulated arterial phase hyperenhancement; tumor washout in the period of portal phase, and noncircular, ill-defined margin Age between 18 and 75 years; The maximum tumor size ≥10 cm, and the total tumor size ≥15 cm; Infiltrative HCC, with PVTT type I or type II or limited metastases (≤5). Child-Pugh class A or B; Eastern Cooperative Group performance status (ECOG) score of 0-2; Hemoglobin ≥ 8.5 g/dL Total bilirubin ≤ 30mmol/L Serum albumin ≥ 32 g/L ASL and AST ≤ 5 x upper limit of normal Serum creatinine ≤ 1.5 x upper limit of normal INR ≤ 1.5 or PT/APTT within normal limits Absolute neutrophil count (ANC) >1,500/mm3 Prothrombin time ≤18s or international normalized ratio < 1.7. Ability to understand the protocol and to agree to and sign a written informed consent document. Exclusion Criteria: HCC with capsule; Extrahepatic metastasis >5; Obstructive PVTT involving the main portal vein. Serious medical comorbidities. Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy Known history of HIV History of organ allograft Known or suspected allergy to the investigational agents or any agent given in association with this trial. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy Evidence of bleeding diathesis. Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.

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: bTAE-HAIC combined with Lenvatinib and Sintilimab<br>bTAE procedure was a 2.8-F microcatheter was super-selectively inserted into the tumor feeding artery using the coaxial technique. Then blank microspheres were used according to the tumor blood supply vessels (40-120um, 100-300um, 300-500um, 500-700um). Hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin every 4 weeks. Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing. Sintilimab, 200 mg intravenously every 3 weeks. | Procedure: bTAE-HAIC<br>* bTAE procedure was a 2.8-F microcatheter was superselectively inserted into the tumor feeding artery using the coaxial technique. Then blank microspheres were used according to the tumor blood supply vessels (40-120um, 100-300um, 300-500um, 500-700um). The microcatheter was reserved at the proper/left/right hepatic artery according tumor location. After the patient returned to the ward, the following FOLFOX-based regime was intra-arterially administered through the microcatheter. The FOLFOX regimen was administered via the hepatic artery as follows: 85 or 135 mg/m2 oxaliplatin from hour 0 to 2 on day 1, and 400 mg/m2 leucovorin from hour 2 to 4 on day 1, and 400 mg/m2 fluorouracil bolus at hour 5 on the day 1; and 2400 mg/m2 fluorouracil over 46 h on days 1 and 2.<br>Drug: Lenvatinib<br>* 12 mg (or 8 mg) once daily (QD) oral dosing.<br>* Other names: TKI inhibits;Drug: Sintilimab<br>* 200mg intravenously every 32 weeks<br>* Other names: programmed cell death protein-1 (PD-1) antibody;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | ORR, as determined based on tumor response according to RECIST 1.1 | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | PFS is defined as the time from the date of inclusion to the date of the first objectively documented tumor progression or death due to any cause. | 6 months | 
| Overall survival (OS) | OS is the length of time from the date of inclusion until death from any cause. | 12 months |