Clinical trial NCT06881433: Immune Checkpoint Inhibitors and Anti-vascular Endothelial Growth Factor Antibody/tyrosine Kinase Inhibitors with or Without HAIC for Advanced HCC
Official title: Immune Checkpoint Inhibitors and Anti-vascular Endothelial Growth Factor Antibody/tyrosine Kinase Inhibitors with or Without Hepatic Arterial Infusion Chemotherapy As First-line Treatment for Advanced Hepatocellular Carcinoma
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hepatocellular Carcinoma (HCC)
Keywords: hepatocellular carcinoma
immune checkpoint inhibitors
molecular target therapies
hepatic infusion chemotherapy
Lead sponsor: Zhongda Hospital
Sponsor class: OTHER
First posted: 2025-03-18
Enrollment: 900
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with unresectable HCC who received HAIC in combination with PD-1/PD-L1 inhibitors and molecular target therapies under real-world practice conditions

Brief summary: Tyrosine kinase inhibitors (TKIs) plus programmed death-1 (PD-1) inhibitors are recommended for patients with advanced hepatocellular carcinoma (HCC) in China. However, these treatments have limited survival benefit in patients with advanced HCC. We aimed to investigate whether hepatic arterial infusion chemotherapy (HAIC) in combination with TKIs and PD-1 inhibitors could improve the efficacy.

Detailed description: The multiple real-world studies have shown that Tyrosine kinase inhibitors (TKIs) plus programmed death-1 (PD-1) inhibitors (TKIs-P) does not result in a high response rate or extended survival for patients with extrahepatic metastases, with an objective response rate (ORR) of less than 20%. Therefore, there is an urgent need to explore effective therapeutic strategies that can enhance the combined antitumor efficacy of TKIs-P and improve the prognosis of patients with advanced hepatocellular carcinoma (HCC). In addition to TKIs-P, more aggressive treatments, such as hepatic arterial infusion chemotherapy (HAIC), have been adopted in the Asia-Pacific region. HAIC significantly increases drug concentration in HCC tissues while decreasing drug distribution in the peripheral blood, thereby improving intrahepatic tumor control and reducing systemic adverse events (AEs). Recent significant advancements have been reported in both local-regional and systemic therapies. Furthermore, the combination of HAIC with TKIs-P (HAIC-TKIs-P) may provide potential synergistic anticancer activity for HCC based on the following rationale: HAIC can effectively kill tumors while promoting the release of tumor antigens, thus transforming "cold tumors" into "hot tumors." At the same time, TKIs can reverse the tumor neovascularization induced by interventional therapies and enhance tumor vasculature normalization. However, it remains unclear whether patients with advanced HCC can benefit from HAIC-TKIs -P through intrahepatic lesion control, thereby impeding tumor progression. Accordingly, this national multiple-centers retrospective study aims to compare the clinical benefits and tolerability of HAIC-TKIs-P versus TKIs-P alone.

Eligibility criteria: Inclusion Criteria:

1. Has a diagnosis of HCC confirmed by radiology, histology, or cytology;
2. Barcelona Clinic Liver Cancer (BCLC) stage B/C;
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. HAIC 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 HAIC 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) per RECIST 1.1 or mRECIST
timeFrame: up to approximately 2 years
Secondary outcomes:
measure: Objective response rate(ORR) per RESCIST 1.1
timeFrame: up to approximately 2 years
measure: ORR per mRECIST
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: