Donafenib Combined With Immunotherapy and Local Therapy for Unresectable Hepatocellular Carcinoma That Has Failed in Previous Therapy

Phase 4

Not yet recruiting

• Conditions: Unresectable Hepatocellular Carcinoma
• Interventions: Drug: Donafenib; Procedure: transhepatic arterial embolization chemotherapy or hepatic arterial infusion chemotherapy; Drug: PD-1,PD-L1

• Registration Number: NCT06496815
• Lead Sponsor: Tongji Hospital

Brief Summary

The goal of this clinical trial is to learn if donafenib combined with or without immunotherapy and local therapy works to treat unresectable hepatocellular carcinoma that has failed in previous therapy.

It will also learn about the safety of donafenib combined with immunotherapy and local therapy.

The main questions it aims to answer are:

The Objective Response Rate (mRecist） and Progression-Free Survival of the participants treated by donafenib combined with immunotherapy and local therapy.

The disease control rate and overall survival of the participants treated by donafenib combined with immunotherapy and local therapy.

The safety of donafenib combined with immunotherapy and local therapy in the participants.

Participants will:

Replace the original targeted drug with donafenib (0.2g bid), while continuing immunotherapy and local therapy as previous therapy (if have).

The observation period was 1 year.

Detailed Description

This is a single-arm, prospective clinical study. 32 patients who had previously received a targeted drug in combination with or without immunotherapy, local therapy (transhepatic arterial embolization chemotherapy (TACE), hepatic arterial infusion chemotherapy (HAIC)) and had not received donafenib will be enrolled. The specific experimental protocol was to replace the original targeted drug with donafenib (0.2g bid), while continuing immunotherapy and local therapy as previous therapy(if have).The observation period was 1 year.

Study Timeline

• Status Verified: 2024-07
• Study First Submitted: 2024-07-04
• Study First Submitted QC: 2024-07-04
• Last Update Submitted: 2024-07-04
• Study First Posted: 2024-07-11
• Last Update Posted: 2024-07-11
• Study Start: 2024-08-01
• Primary Completion: 2026-08-01
• Study Completion: 2027-07-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

1. Voluntarily participate in this study, sign the informed consent form, and be aged between 18 and 70 years old.
2. Have at least one measurable lesion.
3. Clinically and pathologically diagnosed with hepatocellular carcinoma and not suitable for surgical resection.
4. Child-Pugh liver function classification: Class A/Class B.
5. Have previously received targeted therapy (excluding donafenib) in combination or not in combination with immunotherapy, locoregional therapy (transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC)), and have clear tumor progression assessed by two clinicians using the RECIST criteria.
6. If infected with hepatitis B virus (HBV), such as positive for HBsAg, HBV-DNA must be tested, and HBV-DNA must be less than 500 IU/mL; for patients with HBV-DNA greater than 500 IU/mL, at least one week of antiviral treatment is required before randomization (only nucleoside analogs such as entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide tablets are allowed), and the viral copy number should be reduced by more than 10 times compared to before treatment. For HBV infected individuals, antiviral treatment must be received throughout the study period. Patients who are positive for hepatitis C virus (HCV)-RNA must receive antiviral treatment according to the treatment guidelines.
7. Serum bilirubin should be ≤2.0 times the upper limit of normal (ULN); this condition does not apply to patients with confirmed Gilbert's syndrome. Any clinically significant biliary obstruction must be resolved before enrollment in the study.
8. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be ≤2.5 times the ULN. For patients with liver metastases, ALT and AST should be ≤5 times the ULN.

Exclusion Criteria

1. Have an active autoimmune disease or a history of autoimmune disease that may recur (including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism).
2. Use of immunosuppressants or systemic corticosteroid therapy for the purpose of immunosuppression within 2 weeks prior to treatment (dose >10mg/day prednisone or other equivalent efficacy corticosteroids).
3. Patients with congenital or acquired immune function deficiency (such as HIV-infected individuals).
4. Have a history of other primary malignant tumors, except for the following situations: malignant tumors treated with curative intent, known to be inactive for ≥5 years prior to the first study intervention and with a low potential risk of recurrence; basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or malignant melanoma in situ that has been treated with potentially curative intent; or in situ cancer that has been adequately treated with no evidence of disease.
5. Known allergy to any study drug or excipients.
6. Participation in other drug clinical studies within the past 4 weeks.
7. Pregnant or lactating women.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Donafenib combined with or without immunotherapy and local therapy for uHCC	transhepatic arterial embolization chemotherapy or hepatic arterial infusion chemotherapy	The patients who had previously received a targeted drug in combination with or without immunotherapy, local therapy (transhepatic arterial embolization chemotherapy (TACE), hepatic arterial infusion chemotherapy (HAIC)) and had not received donafenib, and the previous treatment has progressed. The specific experimental protocol was to replace the original targeted drug with donafenib (0.2g bid), while continuing immunotherapy and local therapy as previous (if have).
Donafenib combined with or without immunotherapy and local therapy for uHCC	PD-1,PD-L1	The patients who had previously received a targeted drug in combination with or without immunotherapy, local therapy (transhepatic arterial embolization chemotherapy (TACE), hepatic arterial infusion chemotherapy (HAIC)) and had not received donafenib, and the previous treatment has progressed. The specific experimental protocol was to replace the original targeted drug with donafenib (0.2g bid), while continuing immunotherapy and local therapy as previous (if have).
Donafenib combined with or without immunotherapy and local therapy for uHCC	Donafenib	The patients who had previously received a targeted drug in combination with or without immunotherapy, local therapy (transhepatic arterial embolization chemotherapy (TACE), hepatic arterial infusion chemotherapy (HAIC)) and had not received donafenib, and the previous treatment has progressed. The specific experimental protocol was to replace the original targeted drug with donafenib (0.2g bid), while continuing immunotherapy and local therapy as previous (if have).

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (mRecist）(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.
Progression-free survival	an average of 1 year	Patients' progression-free survival after switching to the new treatment regimen is the time between the start of the change and tumor recurrence or death, whichever occurs first

Secondary Outcome Measures

Name	Time	Method
Disease control rate (DCR)	an average of 1 year	Disease control rate (DCR)
Overall Survival (OS)	an average of 1.5 year	The time from the date of initiation of the drug donafenib until the date of death from any cause
Incidence of adverse events and serious adverse events	an average of 1.5 year	Incidence of adverse events and serious adverse events.