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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Donafenib
• Intervention / Treatment: Drug: Donafenib, PD-1; Procedure: TACE

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jian Zhou, M.D., Ph.D.; Phone Number: 13801914007; Email: Zhou.jian@zs-hospital.sh.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Zhongshan Hospital, Fudan University,
      • Contact: Jian Zhou, M.D., Ph.D.; Phone Number: 13801914007; Email: Zhou.jian@zs-hospital.sh.cn
      • Contact: Zhiping Yan, M.D., Ph.D.; Phone Number: 13681971205; Email: yan.zhiping@zs-hospital.sh.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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. Macrovascular invasion involving the main trunk or inferior vena cava, or the presence of bile duct tumor thrombus, 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Donafenib; 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; 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.; Procedure: TACE; TACE will be performed by the investigator based on the patient's tumor status.

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Investigators: Principal Investigator: Jian Zhou, M.D., Ph.D., Zhongshan Hospital, Fudan University, Shanghai, China.; Principal Investigator: Zhiping Yan, M.D., Ph.D., Zhongshan Hospital, Fudan University, Shanghai, China.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 20, 2022
• Primary Completion (Anticipated): March 20, 2024
• Study Completion (Anticipated): May 30, 2024

Study Registration Dates

• First Submitted: February 20, 2022
• First Submitted That Met QC Criteria: February 20, 2022
• First Posted (Actual): March 2, 2022

Study Record Updates

• Last Update Posted (Actual): March 21, 2022
• Last Update Submitted That Met QC Criteria: March 4, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Donafenib
• Other Study ID Numbers: B2021-631R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No