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

Sponsor
Shanghai Zhongshan Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT05262959
Collaborator
(none)
30
Enrollment
1
Location
1
Arm
26.3
Anticipated Duration (Months)
1.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Donafenib, PD-1
  • Procedure: TACE
 Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Anticipated Study Start Date :
Mar 20, 2022
Anticipated Primary Completion Date :
Mar 20, 2024
Anticipated Study Completion Date :
May 30, 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. Progression-free survival 1(PFS 1) [an average of 1 year]

    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.

Secondary Outcome Measures

  1. Time to untreatable progression (TTUP) [an average of 1 year]

    Time from enrollment date to progression without TACE treatment

  2. PFS 2 [an average of 1 year]

    PFS 2 refers to the time from the date of enrollment to tumor progression or death from any cause according to mRECIST.

  3. Objective response rate (ORR) [an average of 1 year]

    According to mRECIST to evaluate the proportion of patients with CR and PR in the total number of patients.

  4. Disease control rate (DCR) [an average of 1 year]

    According to mRECIST to evaluate the proportion of patients with CR、PR and SD in the total number of patients.

  5. Objective response rate (OS) [an average of 1.5 year]

    The time from the date of enrollment to the date of death from any cause.

  6. Incidence of adverse events and serious adverse events. [an average of 1.5 year.]

    Incidence of adverse events and serious adverse events.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts 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≥104copies/ml within 14 days before enrollment, they should take antiviral treatment first, reduce 1 log or reduce to <104copies/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.

  3. 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Zhongshan Hospital, Fudan University, Shanghai Shanghai China 200032

Sponsors and Collaborators

  • 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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Shanghai Zhongshan Hospital
ClinicalTrials.gov Identifier:
NCT05262959
Other Study ID Numbers:
  • B2021-631R
First Posted:
Mar 2, 2022
Last Update Posted:
Mar 21, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Shanghai Zhongshan Hospital
Donafenib
Hepatocellular Carcinoma

Study Results

No Results Posted as of Mar 21, 2022