Donafenib
Conditions
Keywords
Donafenib, Hepatocellular Carcinoma
Brief summary
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.
Interventions
DRUGDonafenib, PD-1
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.
PROCEDURETACE
TACE will be performed by the investigator based on the patient's tumor status.
Sponsors
Shanghai Zhongshan Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients voluntarily enter the study and sign informed consent form (ICF); 2. Age ≥ 18 years and ≤ 75 years, and there is no limit on the gender; 3. Clinically or histologically diagnosed as unresectable HCC; 4. There is at least one measurable lesions that meet the mRECIST standard; 5. Child-pugh classification A or B (score≤7); 6. ECOG : 0 \ 1 ; 7. The number of intrahepatic tumors ≤ 10 and the maximum tumor diameter ≤ 10cm; 8. Previous TACE treatment ≤ 1 time; 9. Life expectancy ≥ 3 months; 10. 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; 11. 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) 1. HB≥90g/L； 2. ANC≥1.5×10\^9/L； 3. PLT≥70×10\^9/L. Biochemical tests are subject to the following criteria: 1. BIL \<1.25xULN ； 2. ALT and AST\<5xULN； 3. Serum creatinine. Less than 1.5 times the upper limit of normal value, Endogenous creatinine clearance\>50ml/min ( Cockcroft-Gault formula)； 4. Albumin≥28g/L； 5. Electrolytes (phosphorus, calcium, magnesium, potassium) ≥ LLN; 6. Urine protein \<2+ or 24-hour urine protein quantitative detection ≤1.0 g/L. Blood coagulation indexes are subject to the following criteria: 1. Prothrombin time (PT) and international normalized ratio (INR) ≤1.5 × ULN; 2. Activated partial thromboplastin time（APTT）≤1.5 × ULN. 12. 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
1. Pathologically confirmed hepatocellular carcinoma intrahepatic cholangiocarcinoma (HCC-ICC) mixed or fibrolamellar hepatocellular carcinoma; 2. The presence of a tumor thrombus in the main portal vein, biliary tract tumor thrombus, inferior vena cava tumor thrombus, or extrahepatic metastasis; 3. Hepatocellular carcinoma recurrence within 2 years after radical resection or ablation; 4. History of malignancy other than HCC within 5 years; 5. Esophageal and/or gastric varices bleeding within 4 weeks prior to initiation of study treatment; 6. Presence of uncontrolled hepatic encephalopathy, hepatorenal syndrome, ascites, pleural effusion, or pericardial effusion; 7. Patients who received liver transplant surgery, prior systemic therapy (chemotherapy, targeted therapy or immunotherapy) or palliative local treatment ≥2 times for HCC； 8. History of organ and cell transplantation； 9. TACE contraindications identified by the investigator; 10. Active severe infection; 11. Autoimmune disease or immune deficiency; 12. Severe organ (heart, kidney) dysfunction; 13. Pregnant or breastfeeding women, and women or men with fertility who are unwilling or unable to take effective contraceptive measures; 14. Unable to follow the research protocol for treatment or scheduled follow-up; Any other researcher who thinks they cannot be included.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival 1(PFS 1) | an average of 1 year | PFS 1 refers to the time from the date of enrollment to the first documented tumor progression as assessed by mRECIST criteria or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) per mRECIST | an average of 1 year | The proportion of patients exhibiting a complete response or partial response to treatment, as assessed by mRECIST. |
| Disease control rate (DCR) per mRECIST | an average of 1 year | The proportion of patients exhibiting a complete response, partial response or stable disease, as assessed by mRECIST. |
| Overall survival (OS) | an average of 1.5 year | The time from the date of enrollment to the date of death from any cause. |
| Adverse events and serious adverse events. | an average of 1.5 year. | Incidence of adverse events and serious adverse events. |
Countries
China
Outcome results
None listed