Clinical trial NCT05262959: A Single Center Study of Donafenib Combined With PD-1 + TACE in the First-line Treatment of aHCC
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Donafenib
Keywords: Donafenib
Hepatocellular Carcinoma
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2022-03-02
Enrollment: 30
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: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free survival 1(PFS 1)
timeFrame: an average of 1 year
Secondary outcomes:
measure: Objective response rate (ORR) per mRECIST
timeFrame: an average of 1 year
measure: Disease control rate (DCR) per mRECIST
timeFrame: an average of 1 year
measure: Overall survival (OS)
timeFrame: an average of 1.5 year
measure: Adverse events and serious adverse events.
timeFrame: an average of 1.5 year.
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University,
state: Shanghai
Study officials:
affiliation: Zhongshan Hospital, Fudan University, Shanghai, China.
name: Jian Zhou, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Zhongshan Hospital, Fudan University, Shanghai, China.
name: Zhiping Yan, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: