Clinical trial NCT06881446: Immune Checkpoint Inhibitors and Anti-vascular Endothelial Growth Factor Antibody/tyrosine Kinase Inhibitors with or Without TACE for Advanced HCC with Vascular Invasions
Official title: Immune Checkpoint Inhibitors and Anti-vascular Endothelial Growth Factor Antibody/tyrosine Kinase Inhibitors with or Without Transarterial Chemoembolization As First-line Treatment for Advanced Hepatocellular Carcinoma with Vascular Invasions
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hepatocellular Carcinoma (HCC)
Keywords: transarterial chemoembolization
hepatocellular carcinoma
immune checkpoint inhibitors
molecular target therapies
Lead sponsor: Zhongda Hospital
Sponsor class: OTHER
First posted: 2025-03-18
Enrollment: 1200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with advanced HCC who received TACE in combination with PD-1/PD-L1 inhibitors and molecular target therapies under real-world practice conditions

Brief summary: Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma with vascular invasions

Detailed description: The vascular invasions is a common complication in 16% to 30% of patients with hepatocellular carcinoma (HCC), contributing to poor prognosis and increasing the risk of cancer recurrence, with a median survival of approximately 2.7 to 4 months without intervention. Both the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases guidelines recommend that HCC patients with vascular invasions be classified as Barcelona Clinic Liver Cancer Stage C and receive systemic treatments. Nevertheless, there is limited data on patients with highly complicated HCC and no optimal treatment strategy for this patient population. Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) are commonly utilized in the systemic therapy of HCC, while the combination of transcatheter arterial chemoembolization (TACE) with systemic therapy has significantly improved treatment outcomes in advanced-stage patients. Therefore, we hypothesized that a triplet regimen comprising TACE, TKI, and ICIs may yield better prognoses for HCC patients with vascular invasions. This study aims to compare the safety and efficacy of the triplet regimen of TKIs, ICIs, and TACE versus Lenvatinib combined with ICIs in advanced-stage HCC with vascular invasions

Eligibility criteria: 1. Has a diagnosis of HCC confirmed by radiology, histology, or cytology;
2. Barcelona Clinic Liver Cancer (BCLC) stage C with the presence of macrovascular invasion;
3. Has not received any previous systemic therapy for HCC (including chemotherapy, molecularly targeted therapy, immunotherapy);
4. Both PD-1/PD-L1 inhibitors and anti-angiogenesis drugs patients received only include marketed drugs but are not limited to HCC approval;
5. TACE was performed after the first PD-1/PD-L1 inhibitor/anti-angiogenic drug treatment or before treatment (within 3 months);
6. Received at least 1 cycle of PD-1/PD-L1 inhibitor/anti-angiogenic drug combination therapy after TACE treatment;
7. Has repeated measurable intrahepatic lesions;

Exclusion Criteria:

1. Cholangiocarcinoma, fibrolamellar, sarcomatoid hepatocellular carcinoma, and mixed hepatocellular/cholangiocarcinoma subtypes(confirmed by histology, or pathology) are not eligible;
2. Unable to meet criteria of combination timeframe described above;
3. Child-Pugh C or PS\>2 or Severe hepatic encephalopathy

Primary outcomes:
measure: Overall Survival(OS)
timeFrame: up to approximately 2 years
measure: Progression free survival(PFS) according to per mRECIST or RECIST 1.1
timeFrame: up to approximately 2 years
Secondary outcomes:
measure: ORR per mRECIST
timeFrame: up to approximately 2 years
measure: Objective response rate(ORR) per RESCIST 1.1
timeFrame: up to approximately 2 years
measure: Adverse event(AE) per Common Terminology Criteria for Adverse Events(CTCAE) 5.0
timeFrame: up to approximately 2 years
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Zhongda Hospital
state: Jiangsu
Study officials:
affiliation: Zhongda hospital, Southeast university, Nanjing, China
name: Gao-Jun Teng, M.D
role: PRINCIPAL_INVESTIGATOR
References: