Clinical trial NCT06715072: Study on the Efficacy and Safety of Transarterial Chemoembolization Combined with Targeted Immunotherapy in Patients with Unresectable Hepatocellular Carcinoma
Official title: Study on the Efficacy and Safety of Transarterial Chemoembolization Combined with Targeted Immunotherapy in Patients with Unresectable Hepatocellular Carcinoma
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Unresectable Liver Cancer
Keywords: Unresectable Liver Cancer
Lead sponsor: Beijing Ditan Hospital
Sponsor class: OTHER
First posted: 2024-12-04
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 68
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Unresectable Liver Cancer

Brief summary: This study is a single-center, single-arm, prospective study. It enrolls patients with unresectable hepatocellular carcinoma (HCC). The study aims to investigate the efficacy and safety of transarterial chemoembolization combined with targeted immunotherapy in patients with unresectable HCC, providing treatment guidance for these patients.

Detailed description: Primary liver cancer (PLC) represents the sixth most common cancer and the third leading cause of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) accounts for 75% to 85% of PLC cases, with the main etiologies being hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Approximately 44-62% of HCC patients develop portal vein tumor thrombus (PVTT), which plays a major role in disease prognosis. These patients have a poor prognosis, with a median survival time of 2.7-4 months without any intervention, posing a significant challenge to clinicians. Both the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) guidelines recommend that HCC patients with PVTT be classified as Barcelona Clinic Liver Cancer stage C (BCLC-C) and receive systemic therapy.For unresectable HCC, trans-arterial chemoembolization (TACE) is one of the most commonly used techniques and can significantly improve survival rates. Compared to best supportive care, TACE can significantly extend the overall survival (OS) of PVTT type I-III HCC by nearly 3 months . Sorafenib, a tyrosine kinase inhibitor (TKI), is the first approved targeted drug and has shown some survival benefits in advanced HCC compared to placebo. The REFLECT trial demonstrated that lenvatinib improved time to progression (TTP) and objective response rate (ORR) compared to sorafenib \[13\]. Two other studies also confirmed that TACE combined with lenvatinib had significantly better clinical efficacy in HCC with PVTT compared to TACE combined with sorafenib.Increasing evidence suggests that immune checkpoint inhibitors (ICIs) combined with multi-kinase TKIs or vascular endothelial growth factor (VEGF) antibodies are becoming a trend in the treatment of advanced HCC. Moreover, the inflammatory factors produced and released during TACE treatment have a priming effect on adaptive immunity; TACE can induce spontaneous T-cell responses and modulate the tumor microenvironment. The combined use of TACE and ICIs may more effectively promote antitumor immune reconstitution. A retrospective study reported that TACE combined with camrelizumab and apatinib significantly improved OS in HCC, with an ORR superior to the dual regimen of apatinib and camrelizumab. Another retrospective study involving 22 patients with advanced HCC showed that using lenvatinib and camrelizumab with TACE could control tumor progression and extend survival. However, data on this triple regimen for treating unresectable hepatocellular carcinoma are limited. Therefore, this study will provide evidence for the triple regimen in treating unresectable hepatocellular carcinoma.

Eligibility criteria: Inclusion Criteria:Voluntarily join this study and sign the informed consent form;Age ≥18 years and ≤68 years, receiving arterial chemoembolization combined with targeted immunotherapy, regardless of gender;At least one measurable lesion as defined by the Modified Response Evaluation Criteria in Solid Tumors (mRECIST);Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1;Child-Pugh score ≤7;Generally good condition, such as albumin \>25 g/L, white blood cells \>3×10\^9/L (excluding causes such as hypersplenism), platelets \>50×10\^9/L, etc.;Expected survival \>12 weeks;No fertility requirements.

Exclusion Criteria:Uncontrolled hypertension;Active autoimmune diseases;Concurrent other untreated malignancies;Pregnant or breastfeeding women;Active bleeding tendency or coagulation disorders;Severe liver, kidney, heart, or bone marrow dysfunction;Severe allergy to iodine contrast agents;Other contraindications to the use of TACE, lenvatinib, camrelizumab, atezolizumab, bevacizumab, etc.;The investigator believes that accompanying medical history may affect the subject's safe completion of the study.

Primary outcomes:
measure: Efficacy Evaluation
timeFrame: tree years
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: Li M, Hao J, Jiang T, Deng W, Lu H, Wang S, Wan G, Xie Y, Yi W. Maternal and neonatal safety of COVID-19 vaccination during the peri-pregnancy period: A prospective study. J Med Virol. 2023 Jan;95(1):e28378. doi: 10.1002/jmv.28378.