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

Fudan University

Status and phase: Completed; Phase 2

Conditions: Donafenib

Treatments: Procedure: TACE; Drug: Donafenib, PD-1

Study type: Interventional

Funder types: Other

Identifiers

NCT05262959

B2021-631R

Details and patient eligibility

About

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.

Enrollment: 30 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

30 participants in 1 patient group

Donafenib

Experimental group

Description:

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.

Treatment:

Drug: Donafenib, PD-1

Procedure: TACE