TACE Versus HAIC, Combined With PD-1 Inhibitors and Lenvatinib for Unresectable Hepatocellular Carcinoma

Official title

TACE Versus HAIC, Combined With PD-1 Inhibitors and Lenvatinib for Unresectable Hepatocellular Carcinoma: a Multicenter, Prospective, Observational Cohort Study

Overview

Although the combination of transarterial chemoembolization (TACE) with PD-1 inhibitor plus lenvatinib has become a new standard, the therapeutic efficacy for unresectable hepatocellular carcinoma (uHCC) still requires improvement, as TACE remains limited for patients with multifocal lesions, hypovascular tumors, or those complicated with portal vein tumor thrombosis (PVTT). Hepatic arterial infusion chemotherapy (HAIC), as an alternative locoregional therapy, has demonstrated advantages in treating these refractory cases. Therefore, this study innovatively designs a prospective cohort study to conduct a comparison of the two triple-combination regimens-"HAIC plus PD-1 inhibitor and lenvatinib" versus "TACE plus PD-1 inhibitor and lenvatinib"-in terms of real-world efficacy and safety, with a focus on enrolling patients who are likely to have suboptimal responses to TACE. This research aims to provide high-level evidence for selecting the optimal combined locoregional strategy for uHCC patients, thereby directly guiding clinical practice and potentially advancing the optimization of treatment strategies and personalized precision medicine to improve patient survival outcomes.

Detailed description

This is a multicenter, prospective, observational cohort study designed to compare the efficacy and safety of transarterial chemoembolization (TACE) versus hepatic arterial infusion chemotherapy (HAIC), each combined with a programmed cell death protein-1 (PD-1) inhibitor and lenvatinib, for the treatment of unresectable hepatocellular carcinoma (uHCC), with a primary focus on progression-free survival (PFS). A total of 364 patients are planned to be enrolled and prospectively followed for efficacy and adverse events. The primary endpoint is PFS. Secondary endpoints include the objective response rate (ORR), overall survival (OS), and safety. Tumor response will be evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST v1.1). Assessments will be performed every 56 days (with a ±3-day window) from the initiation of study treatment until disease progression, patient death, withdrawal of consent, loss to follow-up, or study termination (whichever occurs first). For patients who experience disease progression or initiate other antitumor therapies, survival follow-up will be conducted every 8 weeks (56 days, with a ±7-day window) from the time the event is documented to collect information on subsequent antitumor treatments and survival status until death, withdrawal of consent, loss to follow-up, or study termination.

Interventions

• Procedure TACE
  TACE blocks the tumor's blood supply while delivering high concentrations of chemotherapy agents directly into the hepatic artery. Patients received on-demand TACE until the end of the study or tumor progression.
• Procedure HAIC
  HAIC involves the continuous infusion of high-dose chemotherapy into the hepatic artery via an indwelling catheter, enabling prolonged and deep tumor exposure. Patients received on-demand HAIC until the end of the study or tumor progression.
• Drug PD-1inhibitors
  200mg was given intravenously every three weeks.
• Drug Lenvatinib
  The dose is determined by body weight, body weight greater than or equal to 60kg, 12mg, oral; Less than 60kg, 8mg, orally.

Primary outcome measures

• Progression-free survival (PFS) [Time frame: From the date of enrollment, until the tumor progresses, the patient dies, or the study concludes (whichever occurs first), the assessment period can last up to 60 months.]

Secondary outcome measures (2)

• Overall survival(OS) [Time frame: From date of enrollment until the date of death from any cause, assessed up to 96 months.]
• Objective Response Rate (ORR) [Time frame: From the date of enrollment, until the tumor progresses, the patient dies, or the study concludes (whichever occurs first), the assessment period can last up to 60 months.]

Eligibility criteria

Inclusion criteria

• Aged between 18 and 75 years;
• Tumor stage classified as BCLC-A to -C, with no evidence of extrahepatic metastasis;
• Newly diagnosed, treatment-naïve hepatocellular carcinoma with no prior anticancer therapy;
• Child-Pugh liver function score ≤ 7;
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1;
• Absence of severe organic diseases affecting major organs (e.g., heart, lung, brain).

Exclusion criteria

• Decompensated liver cirrhosis;
• Concurrent other malignancies or recurrent hepatocellular carcinoma;
• Any active, known, or suspected autoimmune disease;
• History of hypersensitivity to any component of PD-1 inhibitors or lenvatinib;
• Human immunodeficiency virus (HIV) infection; or active viral hepatitis (e.g., hepatitis B or C);
• Tumor thrombus involving the inferior vena cava, hepatic veins, or the main portal vein trunk.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07340502 · CHALLENGE-06

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗