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

• Status: Not yet recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Peking Union Medical College Hospital
• Collaborator: Suzhou Zelgen Biopharmaceuticals Co.,Ltd

Criteria

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;