Study on the Safety and Efficacy of Donafinib Combined With Anti-PD-1 Antibody as Adjuvant Therapy for HCC Patients

NCT04418401 | Completed Phase 1

• 1 other identifier: CISLD-8
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, with more than 700,000 new cases in the world every year. China has the highest incidence and death rate of HCC in the world, accounting for 55% of the world's annual incidence and 45% of the world's annual deaths. At present, surgical resection is still one of the most effective treatments for HCC. However, the recurrence rate of tumor after hepatectomy is still very high, and the recurrence rate of 5 years is 60\~70%. Especially in patients with high-risk recurrence factors, without intervention, the cumulative recurrence rate in the first year was about 50%, about 60% in the second year, about 70% in the third year, and about 80% in the fifth year. Tumor recurrence is an important bottleneck that hinders the long-term survival of patients. Therefore, there is an urgent need for effective adjuvant therapy to reduce the postoperative recurrence rate of patients with HCC, especially high-risk patients. However, there is still a lack of standard protocols for postoperative adjuvant therapy for HCC. Here investigators intend to explore the safety and efficacy of Donafinib Combined With Anti-PD-1 Antibody as postoperative adjuvant therapy for HCC patients with high risks of recurrence.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular Carcinoma; Postoperation; High risk of recurrence

Outcome Measures

Primary Outcomes (1)

• Recurrence-free rate in one year

  The cumulative percentage of patients without recurrence in the first year after the primary surgery

  Through the study period, for 3 years

Secondary Outcomes (6)

• Recurrence-free survival

  Through the study period, for 3 years

• Overall survival

  Through the study period, for 3 years

• ECOG physical condition 8/5000 ECOG physical condition

  Through the study period, for 3 years

• FACT-Hep QLQ

  Through the study period, for 3 years

• Alpha fetoprotein

  Through the study period, for 3 years

Study Arms (1)

Experimental group

EXPERIMENTAL

Treatment with Donafenib 100mg PO BID，and anti-PD-1 antibody 3mg/kg ivgtt Q2W. Treatment will last 6 months, unless the tumor recurrence.

Drug: Donafenib and anti-PD-1 antibody

Interventions

Donafenib and anti-PD-1 antibody DRUG

Donafenib was taken orally twice daily, and anti-PD-1 antibody was applied biweekly.

Experimental group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• )Voluntary admission and signature of written informed consent;
• )18\~75 years of age (including 75 years), male and female;
• )Hepatocellular carcinoma underwent radical resection 4\~8 weeks before enrolled.
• )Pathologically diagnosed as hepatocellular carcinoma with any of the following conditions: a)Microvascular invasion (MVI); b)Satellite nodules were found in specimens; c)Multiple tumor nodules(\>3 nodules); d)Portal vein tumor thrombosis (PVTT): The tumor thrombosis invades the left or right branches of portal vein, with or without hepatic vein invasion;
• )≥4 weeks after radical resection, the imaging examination confirmed no recurrence and metastasis.
• )Liver function Child-Pugh grade A (5\~6);
• )Physical condition was scored 0\~1 according to the ECOG criteria.
• )Expected lifetime \>3 months;
• )HBV DNA\<10\^4 copy/ ml (2000 IU/ ml); if HBV DNA ≥10\^4 copy/ ml, antiviral therapy should be given, until the HBV DNA drops below 10\^4Copy/ml patient can be enrolled in the study. And during the study, antiviral drugs should be continued, and liver function and hepatitis B virus load should be monitored;
• )The results of the serum pregnancy test must be negative for women with fertility (i.e. non-menopausal or surgical sterilization) within 7 days prior to the study of drug administration;
• )The main organs function normally: Blood routine examination (no transfusion, no use of G-CSF within 14 days before screening): a)Hemoglobin ≥90 g/L; b)Absolute neutrophil count (ANC)≥1.5×10\^9/L; c)Platelet count ≥75×10\^9/L; Blood biochemical examination (albumin not used within 14 days before screening): d)Albumin ≥28 g/L; e)Total bilirubin ≤1.5× ULN; f)Aspartate aminotransferase (AST), alanine aminotransferase (ALT )≤3× ULN; g)Serum creatinine ≤1.5×ULN; Coagulation function: h)The international standardized ratio (INR) or prothrombin time (PT )≤1.5×ULN;. i)Activated partial thromboplastin time (APTT )≤1.5×ULN.

You may not qualify if:

• Histopathological diagnosis of hepatocellular carcinoma - intrahepatic cholangiocarcinoma (HCC-ICC) mixed type;
• Positive resection margin or tumor rupture;
• Operation of recurrent liver cancer;
• Other malignancies within 5 years unless the patient has received a possible cure and there is no evidence of the disease within 5 years, but this time requirement (i.e. within 5 years) is not applicable to patients with skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ or other carcinoma in situ who have successfully undergone excision;
• Previous or present congenital or acquired immunodeficiency disease;
• History of severe mental illness;
• Suffer from diseases (e.g. severe vomiting, chronic diarrhea, intestinal obstruction, absorption disorders, etc.) that affect the absorption, distribution, metabolism or clearance of the study drug;
• Past or combined medication/treatment:
• Had major surgery (defined by the investigators) within 4 weeks before admission, or expected to require major surgery during study therapy;
• Previous transplantation of allogeneic stem cells or parenchymal organs;
• Preoperative treatment with sorafenib, valvatinib, regofenib or immunomodulator such as anti PD-1、 PD-L1、 anti CTLA-4;
• Patients who have received other systemic anti-tumor treatments before surgery, including traditional Chinese medicine with anti-tumor indications, have had less than 2 weeks or 5 half-time (whichever is longer) between the completion of the treatment and the use of the drugs before the study, or who have not recovered to ≤CTCAE 1 level of adverse events caused by preoperative treatment;
• Other adjuvant therapy (except antiviral therapy) was performed after operation.
• Systemic immunosuppressive drugs have been used within 2 weeks before admission or are expected to be required during the study period, except in the following cases: a)Intra-nasal, inhalation, topical or topical (e.g. intra-articular) corticosteroids; b)Prednisone ≤ 10 mg/day or other equivalent systemic corticosteroid; c)Prophylactic use of corticosteroids for hypersensitivity;
• Take drugs that may prolong QTc and/or induce advanced torsional ventricular tachycardia (Tdp) or affect drug metabolism;

Sponsors & Collaborators

• Zhejiang University: lead

Study Sites (1)

the First Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

donafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Proffessor

Study Record Dates

• First Submitted: June 3, 2020
• First Posted: June 5, 2020
• Study Start: June 11, 2020
• Primary Completion: November 1, 2025
• Study Completion: November 1, 2025
• Last Updated: February 17, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)