Donafenib Combined With Hepatic Artery Chemoembolization for Perioperative Treatment of Liver Transplantation

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of the combination of donafenib and TACE in the perioperative period of liver transplantation.

Detailed Description
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This study plans to enroll about 20 patients with hepatocellular carcinoma (HCC) who do not meet the UCSF standard, they will receive donafenib combined with TACE in downstaging period and donafenib only in adjuvant period. Before the liver transplantation, the safety and efficacy will be evaluated every 3 and 6 weeks, respectively, until liver transplantation or the disease progression that couldn't be treated by TACE. After transplantation, the safety and efficacy will be evaluated every 6 and 12 weeks, respectively, until intolerable toxicity, recurrence or up to 12 months treatment.

Official Title
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Donafenib Combined With Hepatic Artery Chemoembolization for Perioperative Treatment of Liver Transplantation: a Single-arm Exploratory Study

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Donafenib
* Procedure: TACE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of HCC either by biopsy or according to AASLD criteria; At least one measurable lesion according to mRECIST; The previous palliative TACE treatment did not exceed one time, with an interval of ≥ 6 months; For patients who had received one prior TACE treatment, the treated lession progressed or lipiodol deposition was less than 50%; Child-Pugh class ≤ 7; ECOG Performance Status 0-1; Intrahepatic tumors meet any of the following conditions: Beyond the UCSF standard, no more than 5 intrahepatic tumors with the longest diameters ≤ 10cm, no tumor thrombus in the main portal vein Meet the UCSF standard, but AFP > 1000 ng / ml Exclusion Criteria: The pathological diagnosis was hepatocellular carcinoma intrahepatic cholangiocarcinoma (HCC-ICC) mixed type or fibrous lamellar hepatocellular carcinoma; There were inferior vena cava cancer thrombus, hepatic vein cancer thrombus, regional lymph node invasion or extrahepatic metastasis; HCC recurred within 2 years after radical resection or ablation; Patients who have received prior liver transplantation, ≥ 2 times of palliative TACE or other palliative local treatment (including HAIC, radiotherapy, etc.), but who have received prior radical hepatectomy, radical ablation and preventive TACE for the purpose of anti-recurrence can be enrolled; Prior or ongoing systemic therapy (including systemic therapeutic drugs under research, excluding antiviral therapy), including but not limited to TKI such as sorafenib, lenvatinib, regofinib, apatinib, and ambrotinib, PD-1 / PD-L1 monoclonal antibody or immunotherapy against PD-1 / PD-L1, etc; There are contraindications to TACE determined by the investigators (e.g., portal vein trunk obstruction without formation of collateral vessels, etc.);

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: Donafenib<br>Donafenib combine with TACE for downstaging treatment; Donafenib for adjuvant therapy. | Drug: Donafenib<br>* 0.2g BID for downstaging treatment; 0.1g BID for adjuvant therapy<br>Procedure: TACE<br>* For downstaging treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Downstaging success rate | Definition of successful downstaging: those who meet the UCSF standard with baseline AFP > 1000 ng/ml need to be reduced to < 500 ng/ml. | Immediately after downstaging treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate before transplantation (ORR) |  | 1 year | 
| Complete pathological response rate (pCR) |  | 1 year | 
| Recurrence-free survival (RFS) | Including median RFS, 1, 2, 3-years RFS rate | 3 years | 
| Overall survival (OS) | Including median OS, 1, 2, 3-years OS rate | 3 years | 
| Adverse events |  | 3 years |