Clinical trial NCT05576909: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Lead sponsor: Beijing Tsinghua Chang Gung Hospital
Sponsor class: OTHER
Collaborators: name: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
First posted: 2022-10-13
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.);

Primary outcomes:
measure: Downstaging success rate
timeFrame: Immediately after downstaging treatment
Secondary outcomes:
measure: Objective response rate before transplantation (ORR)
timeFrame: 1 year
measure: Complete pathological response rate (pCR)
timeFrame: 1 year
measure: Recurrence-free survival (RFS)
timeFrame: 3 years
measure: Overall survival (OS)
timeFrame: 3 years
measure: Adverse events
timeFrame: 3 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tsinghua Changgung Hospital
Study officials:
References: