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

NCT ID: NCT06496815

Last Updated: 2024-07-11

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-01
• Study Completion Date: 2027-07-30

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.

Conditions

Unresectable Hepatocellular Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Donafenib combined with or without immunotherapy and local therapy for uHCC

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).

Group Type: EXPERIMENTAL

Donafenib

Intervention Type: DRUG

Donafenib will be taken orally twice a day, 0.2g each time.

transhepatic arterial embolization chemotherapy or hepatic arterial infusion chemotherapy

Intervention Type: PROCEDURE

Eligible subjects will receive transhepatic arterial embolization chemotherapy or hepatic arterial infusion chemotherapy as previous (if have).

PD-1,PD-L1

Intervention Type: DRUG

PD-1/PD-L1 will be used as previous (if have).

Interventions

Donafenib

Donafenib will be taken orally twice a day, 0.2g each time.

Intervention Type: DRUG

transhepatic arterial embolization chemotherapy or hepatic arterial infusion chemotherapy

Eligible subjects will receive transhepatic arterial embolization chemotherapy or hepatic arterial infusion chemotherapy as previous (if have).

Intervention Type: PROCEDURE

PD-1,PD-L1

PD-1/PD-L1 will be used as previous (if have).

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tongji Hospital

OTHER

Sponsor Role: lead

Responsible Party

Zhiyong Huang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhiyong Huang

Role: PRINCIPAL_INVESTIGATOR

Tongji Hospital

Central Contacts

Zhiyong Huang

Role: CONTACT

Zyhuang126@126.com

86-13995507729

Zunyi Zhang

Role: CONTACT

zunyizhang@tjh.tjmu.edu.cn

86-15827413728

Other Identifiers

uHCC-Dona-TJ01

Identifier Type: -

Identifier Source: org_study_id