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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Donafenib; Procedure: TACE

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lu Qian; Phone Number: 15810088530; Email: luqianbtch@163.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Tsinghua Changgung Hospital
    • Contact: Lu Qian

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of HCC either by biopsy or according to AASLD criteria;
2. At least one measurable lesion according to mRECIST;
3. 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%;
4. Child-Pugh class ≤ 7;
5. ECOG Performance Status 0-1;

6. 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:

1. The pathological diagnosis was hepatocellular carcinoma intrahepatic cholangiocarcinoma (HCC-ICC) mixed type or fibrous lamellar hepatocellular carcinoma;
2. There were inferior vena cava cancer thrombus, hepatic vein cancer thrombus, regional lymph node invasion or extrahepatic metastasis;
3. HCC recurred within 2 years after radical resection or ablation;
4. 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;
5. 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;
6. There are contraindications to TACE determined by the investigators (e.g., portal vein trunk obstruction without formation of collateral vessels, etc.);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Donafenib; Donafenib combine with TACE for downstaging treatment; Donafenib for adjuvant therapy.	Drug: Donafenib; 0.2g BID for downstaging treatment; 0.1g BID for adjuvant therapy; Procedure: TACE; For downstaging treatment

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Beijing Tsinghua Chang Gung Hospital
• Collaborators: Suzhou Zelgen Biopharmaceuticals Co.,Ltd

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2023
• Primary Completion (Estimated): October 15, 2024
• Study Completion (Estimated): October 15, 2025

Study Registration Dates

• First Submitted: August 14, 2022
• First Submitted That Met QC Criteria: October 8, 2022
• First Posted (Actual): October 13, 2022

Study Record Updates

• Last Update Posted (Actual): July 13, 2023
• Last Update Submitted That Met QC Criteria: July 11, 2023
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma, Hepatocellular
• Other Study ID Numbers: DPM-HCC-N03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No