Hepatic Artery Infusion Chemotherapy Plus Donafenib in Patients With Hepatocellular Carcinoma After Surgery

Sponsor

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04962958

Collaborator

Meng Chao Hepatobiliary Hospital of Fujian Medical University (Other), Huashan Hospital (Other), The Second Affiliated Hospital of Harbin Medical University (Other)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open-label，multi-center ，non-randomized ，single arm exploratory study . This clinical study is an investigator-initiated clinical trial（IIT ）. The objective of this study is to evaluate if the addition of hepatic artery infusion chemotherapy (HAIC) and Donafenib after curative resection for hepatocellular carcinoma patients with a solitary tumor≥5 cm and microvascular invasion （MVI） will prevent or delay the recurrence of the disease.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma Carcinoma, Hepatocellular Liver Neoplasms Digestive System Neoplasms Antineoplastic Agents Donafenib Fluorouracil Oxaliplatin Antimetabolites	Procedure: Hepatic arterial infusion chemotherapy Drug: Folfox Protocol Drug: Donafenib	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Prospective, Single-arm, Multicenter Clinical Study of Hepatic Artery Infusion Chemotherapy With Donafenib for Adjuvant Treatment of HCC Patients With High Risk of Recurrence After Hepatectomy.

Anticipated Study Start Date :

Nov 1, 2021

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Aug 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HAIC+Donafenib Donafenib combined with Hepatic arterial infusion chemotherapy with Folfox Protocol	Procedure: Hepatic arterial infusion chemotherapy administration of Oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries Other Names: HAIC Drug: Folfox Protocol Oxaliplatin , fluorouracil, and leucovorin Other Names: Oxaliplatin , fluorouracil, and leucovorin Drug: Donafenib administration of Donafenib

Arm

Intervention/Treatment

Experimental: HAIC+Donafenib

Donafenib combined with Hepatic arterial infusion chemotherapy with Folfox Protocol

Procedure: Hepatic arterial infusion chemotherapy

administration of Oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries

Other Names:

HAIC

Drug: Folfox Protocol

Oxaliplatin , fluorouracil, and leucovorin

Other Names:

Oxaliplatin , fluorouracil, and leucovorin

Drug: Donafenib

administration of Donafenib

Outcome Measures

Primary Outcome Measures

2-year cumulative recurrence-free survival rate [2-year]
This is defined as the length of time (days) that the patient survives since study registration without any signs or symptoms of locoregional HCC assessed by structured clinical and radiological (clinical) follow-up . If at close-out date of the study, there are no signs of locoregional recurrence, the patient will be censored to the date of the most recent follow-up examination. The 2-year cumulative incidence rates will be estimated from the curves and its associated 95% confidence intervals will be calculated.

Secondary Outcome Measures

1-year recurrence-free survival rate [1-year]
This is defined as the length of time (days) that the patient survives since study registration without any signs or symptoms of locoregional HCC assessed by structured clinical and radiological (clinical) follow-up . If at close-out date of the study, there are no signs of locoregional recurrence, the patient will be censored to the date of the most recent follow-up examination. The 1-year cumulative incidence rates will be estimated from the curves and its associated 95% confidence intervals will be calculated.
Disease-free survival [2-year]
from the date of enrollment to tumor recurrence or Death
Overall Survival [approximately 60 months from first patient first visit]
from the date of enrollment to Death
Adverse Events [30 days]
Number of adverse events. Postoperative adverse events were graded based on CTCAE v5.0

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Aged 18-75 years, male or female;
Naive patients with hepatocellular carcinoma pathologically diagnosed who have Underwent radical hepatectomy 4-8 weeks before enrollment;
HCC patients with a solitary tumor≥5 cm and Microvascular invasion;
Child-Pugh score A/B(≤7);
ECOG PS score 0-1;
No residual tumor lesions were confirmed on imaging more than 4 weeks after surgery;
The main organ functions meet the following criteria within 14 days before enrollment; (1)Hemoglobin(HB)≥100 g/L (2)neutrophils(ANC)≥1.5×10^{9 /L, (3)platelet
count(PLT)≥75×10}9/L; (4)ALB≥28g/L (5)alanine aminotransferase(ALT), aspartate aminotransferase(AST)<5×ULN (6)Total bilirubin (TBIL)<1.5×ULN (7)Plasma creatinine ≤1.5×ULN with a creatinine clearance≥50mL/min (8)Activation Partial Thrombin Activation Time (APTT) and International Normalized Ratio (INR)≤1.5×ULN
Subjects voluntarily enrolled in the study, signed an informed consent form, followed well and cooperated with the follow-up

Exclusion Criteria:

Patients who have received any hepatocellular carcinoma-related systemic therapy before enrollment; including targeted therapy such as sorafenib, lenvatinib, and regorafenib, or immunomodulators such as anti-PD-1, anti-PD-L1, and anti-CTLA-4 Treatment, excluding antiviral treatment; if the patient has used traditional Chinese medicine with anti-tumor indications, it must be> 2 weeks or 5 drug half-lives (whichever is longer). Patients whose adverse events caused by treatment have not recovered to ≤ CTCAE Grade 1;
Patients who have received other adjuvant treatments (except antiviral therapy) after radical hepatectomy, including adjuvant local treatments (such as transarterial chemoembolization [TACE]);
Hepatic veins, portal veins, bile ducts, or inferior vena cava can be visually or microscopically seen with tumor thrombi
Diagnosed with lymph node invasion or extrahepatic metastasis;
Number of tumors≥2;
A history of other malignant tumours within the last five years, except for cured skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ or other carcinoma in situ;
Pregnant or breastfeeding women; males or females of childbearing age who are unwilling or unable to take effective contraceptive measures
Known history of alcohol, psychotropic drug or other drug abuse within 6 months before entry into the study 9.Those the researcher deems inappropriate for inclusion.