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

Primary Purpose

Hepatocellular Carcinoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Donafenib
TACE
Sponsored by
Beijing Tsinghua Chang Gung Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.);

Sites / Locations

  • Beijing Tsinghua Changgung HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Donafenib

Arm Description

Donafenib combine with TACE for downstaging treatment; Donafenib for adjuvant therapy.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Objective response rate before transplantation (ORR)
Complete pathological response rate (pCR)
Recurrence-free survival (RFS)
Including median RFS, 1, 2, 3-years RFS rate
Overall survival (OS)
Including median OS, 1, 2, 3-years OS rate
Adverse events

Full Information

First Posted
August 14, 2022
Last Updated
July 11, 2023
Sponsor
Beijing Tsinghua Chang Gung Hospital
Collaborators
Suzhou Zelgen Biopharmaceuticals Co.,Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05576909
Brief Title
Donafenib Combined With Hepatic Artery Chemoembolization for Perioperative Treatment of Liver Transplantation
Official Title
Donafenib Combined With Hepatic Artery Chemoembolization for Perioperative Treatment of Liver Transplantation: a Single-arm Exploratory Study
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 30, 2023 (Actual)
Primary Completion Date
October 15, 2024 (Anticipated)
Study Completion Date
October 15, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Beijing Tsinghua Chang Gung Hospital
Collaborators
Suzhou Zelgen Biopharmaceuticals Co.,Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Donafenib
Arm Type
Experimental
Arm Description
Donafenib combine with TACE for downstaging treatment; Donafenib for adjuvant therapy.
Intervention Type
Drug
Intervention Name(s)
Donafenib
Intervention Description
0.2g BID for downstaging treatment; 0.1g BID for adjuvant therapy
Intervention Type
Procedure
Intervention Name(s)
TACE
Intervention Description
For downstaging treatment
Primary Outcome Measure Information:
Title
Downstaging success rate
Description
Definition of successful downstaging: those who meet the UCSF standard with baseline AFP > 1000 ng/ml need to be reduced to < 500 ng/ml.
Time Frame
Immediately after downstaging treatment
Secondary Outcome Measure Information:
Title
Objective response rate before transplantation (ORR)
Time Frame
1 year
Title
Complete pathological response rate (pCR)
Time Frame
1 year
Title
Recurrence-free survival (RFS)
Description
Including median RFS, 1, 2, 3-years RFS rate
Time Frame
3 years
Title
Overall survival (OS)
Description
Including median OS, 1, 2, 3-years OS rate
Time Frame
3 years
Title
Adverse events
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.);
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lu Qian
Phone
15810088530
Email
luqianbtch@163.com
Facility Information:
Facility Name
Beijing Tsinghua Changgung Hospital
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lu Qian

12. IPD Sharing Statement

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

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