Donafenib Combined With TACE as Adjuvant Therapy of Patients With Hepatocellular Carcinoma

December 2, 2021 updated by: Peking Union Medical College Hospital

Efficacy and Safety of Donafenib Combined With TACE as Adjuvant Therapy of Patients With Hepatocellular Carcinoma at a High Risk of Recurrence After Radical Resection

The investigators design a phase IIB clinical study to explore the efficacy and safety of Donafenib combined with TACE as adjuvant therapy of patients with hepatocellular carcinoma at a high risk of recurrence after radical resection.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This trial is a single-arm, non-randomized and single-center clinical study of targeted therapy combined TACE in patients with hepatocellular carcinoma at a high risk of recurrence after radical resection.It is estimated that 30 patients who met the study criteria will be enrolled in Peking Union Medical College Hospital(PUMCH) and treated with Donafenib and TACE. The investigators will follow up and collect subjects' data monthly to evaluate the efficacy and safety of treatment, including overall survival and time to progression.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Beijing, China
        • Chinese Academy of Medical Sciences & Peking Union Medical College Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age 18 ~ 75 years old (including boundary value), male and female;
  2. Radical resection of liver cancer and intraoperative ablation of tumors ≤ 2cm were performed 4 ~ 8 weeks before enrollment;

  3. Hepatocellular carcinoma diagnosed by pathology and meeting at least one of the following conditions:

    1. Single tumor with tumor size ≥ 5cm;
    2. Pathology showed microvascular invasion (MVI);
    3. Satellite foci were found in the specimens;
    4. Multiple lesions (≥ 3);
    5. AFP ≥ 400 ng / ml one week before operation
    6. Preoperative imaging and / or intraoperative or postoperative pathological reports found PVTT type I: tumor thrombus invaded the secondary and above branches of portal vein;
  4. No anti-tumor treatment was received before operation;
  5. Liver function grade child Pugh a;
  6. Physical condition (PS) score of Eastern cancer cooperation group (ECoG) was 0-1;
  7. Imaging examination ≥ 4 weeks after operation confirmed that there was no recurrence and metastasis;
  8. The estimated survival time shall not be less than 3 months;

  9. With sufficient organ function reserve, the laboratory test values within 14 days before treatment must meet the following standards:

    1. Blood routine examination: Hb≥100 g/L; ANC≥1.5 × 109 /L; PLT≥75 × 109 /L
    2. Biochemical examination: ALB ≥28g/L; ALT and AST < 5 × ULN; TBIL ≤2 × ULN; creatinine ≤ 1.5 × ULN or creatinine clearance (CCR) ≥ 50 ml / min
    3. The electrolyte is basically normal or normal after treatment;
    4. Urinary protein < 2 + or 24-hour urinary protein quantitative test ≤ 1.0 g / L (for patients with urinary protein ≥ 2 +, 24-hour urinary protein quantitative test should be carried out, and they can be selected only when it is ≤ 1.0 g / L);
    5. Coagulation function:

    international standard ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN activated partial coagulation time (APTT) ≤ 1.5 × ULN

  10. Patients with HBsAg positive should continue antiviral treatment after operation and take first-line antiviral drugs such as entecavir or tenofovir or propofol tenofovir fumarate;
  11. The patients were enrolled voluntarily, could provide written informed consent, and could understand and comply with the trial protocol to follow-up.

Exclusion Criteria:

  1. The pathological diagnosis was fiberboard HCC, sarcomatoid HCC, hepatocellular carcinoma intrahepatic cholangiocarcinoma (HCC-ICC);
  2. Positive margin or tumor rupture;
  3. Reoperation of recurrent liver cancer;
  4. Previous liver transplantation;
  5. AFP did not return to normal at 4 weeks and did not return to normal at 6 weeks after operation;
  6. Previously received systemic therapy for HCC, including targeted drug therapy such as Sorafenib, Lenvatinib and Regorafenib, or immunotherapy such as anti-PD-1, anti-PD-L1 and anti-CTLA-4, except antiviral therapy; If the patient has previously used traditional Chinese medicine with anti-tumor indications, it must be more than 4 weeks after the completion of treatment and before the medication in this study, and the adverse events caused by treatment have not recovered to ≤ CTCAE level 1;
  7. Received other adjuvant therapy (except antiviral therapy), including adjuvant local therapy;
  8. There were tumor thrombi in the main portal vein and primary branches, inferior vena cava, hepatic vein or bile duct, lymph node invasion or extrahepatic metastasis before operation;
  9. 5 years of suffering from other malignancies, unless the patient has received the possibility of curative treatment and there is no evidence of the disease within 5 years, the time requirement (i.e. 5 years) does not apply to successful basal cell carcinoma, cutaneous squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ or other orthotopic cancer.
  10. Previous history of severe mental illness;
  11. Suffering from diseases affecting the absorption, distribution, metabolism or clearance of the study drug (such as severe vomiting, chronic diarrhea, intestinal obstruction, absorption disorder, etc.);
  12. Taking drugs that may prolong QTc and / or induce tip twist transition ventricular tachycardia (TDP) or drugs that affect drug metabolism at the same time;
  13. The patient has known or suspected allergy to tyrosine kinase inhibitor (TKI) drugs, or is allergic to the excipients of the study drugs;
  14. There are uncontrollable hepatic encephalopathy, hepatorenal syndrome, ascites, pleural effusion or pericardial effusion;
  15. Have active bleeding or abnormal coagulation function, have bleeding tendency or are receiving thrombolytic, anticoagulant or antiplatelet therapy;
  16. Have a history of gastrointestinal hemorrhage or have a clear tendency of gastrointestinal bleeding in the past 4 weeks (e.g. local active ulcer lesions, fecal occult blood + + or more, gastroscopy should be performed if continuous fecal occult blood +, or other conditions that may cause gastrointestinal bleeding determined by the researcher (e.g. severe gastric fundus / esophageal varices);
  17. Gastrointestinal perforation, abdominal fistula or abdominal abscess occurred in the past 6 months;
  18. Thrombosis or thromboembolism events occurred in the past 6 months, such as stroke and / or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc;

  19. Uncontrolled cardiovascular disease judged by the researcher. Including but not limited to the following situations:

    1. acute myocardial infarction in the past 6 months;
    2. Severe / unstable angina pectoris or coronary artery bypass grafting;
    3. Congestive heart failure (NYHA > 2);
    4. Arrhythmias with poor control or requiring pacemaker treatment;
    5. Hypertension (systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHg) ";

  20. Active infection requiring treatment

    1. Active hepatitis B (HBsAg positive and abnormal liver function): if the HBV-DNA is ≥ 104 copies / ml within 14 days before treatment, the patient shall first undergo antiviral treatment, reduce it to < 104 copies / ml, and then enter the study, continue antiviral treatment and monitor liver function and serum HBV-DNA level;
    2. Active hepatitis C (HCV-RNA ≥ 103 copies / ml) with abnormal liver function [ALT or ast > 3 × ULN with TBIL > 2 × ULN or clinical jaundice]);
  21. pregnant or lactating women, and female or male patients with fertility are unwilling or unable to take effective contraceptive measures;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental: Donafenib plus TACE

Donafenib: 4-8 weeks after radical surgery,patients will take donafenib, 200mg Bid,at least 6 months.

TACE:4-8 weeks after radical surgery,Patients will receive TACE once.
Drug: Donafenib

Donafenib: 4-8 weeks after radical surgery,patients will take donafenib, 200mg Bid,at least 6 months.

TACE:4-8 weeks after radical surgery,patients will receive TACE once.

Other Names:
  • TACE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
1 year RFS rate
Time Frame: 1 year
1 year relapse-free survival rate
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
RFS
Time Frame: 3 years
Recurrence Free Survival
3 years
OS
Time Frame: 3 years
Overall Survival
3 years
TTR
Time Frame: 3 years
Time To Recurrence
3 years
2/3 year RFS rate
Time Frame: 2/3 years
2/3 year Recurrence free survival rate
2/3 years
AE
Time Frame: 3 years
Adverse events
3 years
AFP
Time Frame: 3 years
Alpha fetal protein
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking Union Medical College Hospital

Collaborators

Suzhou Zelgen Biopharmaceuticals Co.,Ltd

Investigators

  • Principal Investigator: Yilei Mao, MD, Peking Union Medical College Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

December 1, 2021

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

December 1, 2024

Study Registration Dates

First Submitted

December 2, 2021

First Submitted That Met QC Criteria

December 2, 2021

First Posted (Actual)

December 17, 2021

Study Record Updates

Last Update Posted (Actual)

December 17, 2021

Last Update Submitted That Met QC Criteria

December 2, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SH3137

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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