A Single Center Study of Donafenib Combined With PD-1 + TACE in the First-line Treatment of aHCC

Study Overview
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Brief Summary
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This study is expected to recruit 30 patients with unresectable HCC who will be treated with Donafenib combined with PD-1 + TACE. During the study period, the tumor efficacy and resectability will be evaluated by imaging examination every 6 weeks. Patients with successful transformation can choose hepatectomy or observation. During the study, safety evaluation and effectiveness evaluation will be carried out.

Official Title
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A Single Center Study of Donafenib Combined With Programmed Cell Death-1 （PD-1） + Transarterial Chemoembolization (TACE) in the First-line Treatment of Advanced Hepatocellular Carcinoma (aHCC)

Conditions
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Donafenib

Intervention / Treatment
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* Drug: Donafenib, PD-1
* Procedure: TACE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients voluntarily enter the study and sign informed consent form (ICF); Age ≥ 18 years and ≤ 75 years, and there is no limit on the gender; Clinically or histologically diagnosed as unresectable HCC; There is at least one measurable lesions that meet the mRECIST standard; Child-pugh classification A or B (score≤7); ECOG : 0   1 ; The number of intrahepatic tumors ≤ 10 and the maximum tumor diameter ≤ 10cm; Previous TACE treatment ≤ 1 time; Life expectancy ≥ 3 months; For patients with HBV infection, if HBV-DNA is≥10^4copies/ml within 14 days before enrollment, they should take antiviral treatment first, reduce 1 log or reduce to <10^4copies/ml before entering the study, and continue antiviral treatment and monitor liver function and serum HBV-DNA levels; Baseline blood routine and biochemical indexes meet the following criteria within 14 days before treatment: Blood routine examination criteria must be met: (no blood transfusion within 14 days) HB≥90g/L； ANC≥1.5×10^9/L； PLT≥70×10^9/L. Biochemical tests are subject to the following criteria: BIL <1.25xULN ； ALT and AST<5xULN； Serum creatinine. Less than 1.5 times the upper limit of normal value, Endogenous creatinine clearance>50ml/min ( Cockcroft-Gault formula)； Albumin≥28g/L； Electrolytes (phosphorus, calcium, magnesium, potassium) ≥ LLN; Urine protein <2+ or 24-hour urine protein quantitative detection ≤1.0 g/L. Blood coagulation indexes are subject to the following criteria: Prothrombin time (PT) and international normalized ratio (INR) ≤1.5 × ULN; Activated partial thromboplastin time（APTT）≤1.5 × ULN. The serum pregnancy test results of female patients with fertility (referring to premenopausal or non surgical sterilization) must be negative within 14 days before enrollment. Exclusion Criteria: Pathologically confirmed hepatocellular carcinoma intrahepatic cholangiocarcinoma (HCC-ICC) mixed or fibrolamellar hepatocellular carcinoma; Macrovascular invasion involving the main trunk or inferior vena cava, or the presence of bile duct tumor thrombus, extrahepatic metastasis; Hepatocellular carcinoma recurrence within 2 years after radical resection or ablation; History of malignancy other than HCC within 5 years; Esophageal and/or gastric varices bleeding within 4 weeks prior to initiation of study treatment; Presence of uncontrolled hepatic encephalopathy, hepatorenal syndrome, ascites, pleural effusion, or pericardial effusion; Patients who received liver transplant surgery, prior systemic therapy (chemotherapy, targeted therapy or immunotherapy) or palliative local treatment ≥2 times for HCC； History of organ and cell transplantation； TACE contraindications identified by the investigator; Active severe infection; Autoimmune disease or immune deficiency; Severe organ (heart, kidney) dysfunction; Pregnant or breastfeeding women, and women or men with fertility who are unwilling or unable to take effective contraceptive measures; Unable to follow the research protocol for treatment or scheduled follow-up; Any other researcher who thinks they cannot be included.

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: 0.1g po. BID. And it will be taken on the first day of the study. PD-1: 200mg ivgtt. Q3W. It will be used at the same time as Donafenib. TACE: The first treatment will be carried out 2-3 weeks after taking Donafenib. | Drug: Donafenib, PD-1<br>* Eligible subjects will receive Donafenib combined with PD-1 and TACE. Donafenib will be taken orally twice a day, 0.1mg each time.PD-1 will be used intravenously every 3 weeks.<br>Procedure: TACE<br>* TACE will be performed by the investigator based on the patient's tumor status.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival 1(PFS 1) | PFS 1 refers to the time from the date of registration to the progression of tumors that cannot be treated by TACE or death from any cause. | an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to untreatable progression (TTUP) | Time from enrollment date to progression without TACE treatment | an average of 1 year | 
| PFS 2 | PFS 2 refers to the time from the date of enrollment to tumor progression or death from any cause according to mRECIST. | an average of 1 year | 
| Objective response rate (ORR) | According to mRECIST to evaluate the proportion of patients with CR and PR in the total number of patients. | an average of 1 year | 
| Disease control rate (DCR) | According to mRECIST to evaluate the proportion of patients with CR、PR and SD in the total number of patients. | an average of 1 year | 
| Objective response rate (OS) | The time from the date of enrollment to the date of death from any cause. | an average of 1.5 year | 
| Incidence of adverse events and serious adverse events. | Incidence of adverse events and serious adverse events. | an average of 1.5 year. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Donafenib, Hepatocellular Carcinoma