Triple Therapy for Intermediate-advanced HCC With BDTT (TALENP002)

Official title

Transcatheter Arterial Chemoembolization Combined With Lenvatinib Plus Tislelizumab for Intermediate-advanced Hepatocellular Carcinoma With Bile Duct Tumor Thrombus: A Multicenter, Single-arm, Real-world Study

Overview

This is a multicenter, Single-arm, Real-world Study to evaluate the efficacy and safety of Transcatheter arterial chemoembolization (TACE), Lenvatinib combined with Tislelizumab (Triple Therapy) for patients with Hepatocellular Carcinoma (HCC) with bile duct tumor thrombus (BDTT).

Detailed description

Surgical resection is considered to be the treatment of choice for Hepatocellular Carcinoma (HCC) combined with bile duct tumor thrombus (BDTT), but a significant proportion of patients with HCC combined with BDTT are unable to undergo surgical treatment at the time of initial diagnosis. For patients with unresectable advanced HCC combined with BDTT, conversion therapy is particularly important. Currently, there is relatively little literature related to the conversion treatment of HCC with BDTT. Several studies have confirmed that the transcatheter arterial chemoembolization (TACE), lenvatinib, combined with Tislelizumab (Triple Therapy) for the treatment of intermediate-advanced HCC can achieve better efficacy with an acceptable safety. However, there are no clinical studies or relevant literature reports on Triple Therapy for the treatment of HCC with BDTT. The present study is a multicenter, Single-arm, Real-world Study designed to evaluate the efficacy and safety of a triple therapy for the treatment of patients with HCC with BDTT.

Interventions

• Combination product TACE, Lenvatinib, combined with Tislelizumab group
  TACE, Lenvatinib \[8mg(\<60kg)/12mg(\>60kg) orally daily\] combination with Tislelizumab (200mg administered intravenous injection on Day 1 of each 21-day cycle). After the triple therapy, surgical resection is an option if assessed by the investigator to be feasible, or continued until disease progression or intolerable if not.

Primary outcome measures

• Objective response rate, ORR [Time frame: Four weeks after the initiation of medication until the day before surgery]

Secondary outcome measures (5)

• Overall survival, OS [Time frame: From date of enrollment until the date of death from any cause, assessed up to 60 months]
• Progression free survival, PFS [Time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months]
• The Disease control rate, DCR [Time frame: Four weeks after the initiation of medication until the day before surgery]
• Conversion resection rate, CRR [Time frame: Four weeks after the initiation of medication until the day before surgery]
• Toxicity Adverse events [Time frame: From the initiation of medication, with recordings made whenever an adverse reaction occurs, assessed up to 12 months]

Eligibility criteria

Inclusion criteria

• Age between 18 and 75 years old;
• Patients with clinical diagnosis of Hepatocellular Carcinoma (HCC) combined with bile duct tumor thrombus (BDTT) (refer to the diagnostic criteria of the Chinese Expert Consensus on Multidisciplinary Diagnosis and Treatment of HCC with BDTT (2020 Edition)), BCLC Stage B or Stage C, and unresectable HCC (decided after multidisciplinary discussion);
• Patients who had not received any tumor-related targeted, immunotherapy, radiotherapy and chemotherapy before enrollment;
• Patients with at least one measurable lesion according to the mRECIST criteria (measurable lesion with a CT/MRI scan length diameter ≥ 10 mm and measurable lesion has not received localized treatment such as TACE, radiofrequency, cryotherapy, etc.);
• ECOG score: 0-1;
• liver function Child-Pugh class A or B; if combined with obstructive jaundice, total bilirubin ≤50umol/L is required. If higher than 50umol/L, biliary drainage is recommended;
• Blood routine: absolute neutrophil count ≥1.5×10\^9/L, Hb≥8.5g/L, PLT≥75×10\^9/L;
• No history of severe cardiac arrhythmia or heart failure; no history of severe ventilatory dysfunction or severe pulmonary infection; no acute or chronic renal failure with creatinine clearance >40mL/min;
• Expected survival time greater than 3 months.

Exclusion criteria

• The tumor with extrahepatic metastasis or invaded adjacent organs;
• Patients received other anti-tumor treatments;
• Existence of contraindications to TACE;
• History of allergy to the components or excipients of Lenvatinib or Tislelizumab;
• The patient has any active autoimmune disease or has an autoimmune disease with expected relapse. Patients are on immunosuppressive or systemic hormone therapy for immunosuppression;
• Patients with proteinuria suggestive of ≥ 1 + in routine urine will undergo a 24-hour urine protein test for patients with ≥ 1 g of 24-hour urine protein;
• Patients with co-morbidities of other malignant tumors;
• Patients with co-morbid psychiatric disorders;
• Patients with pregnant or lactating women;
• Patients with organ transplant patients;
• Patients with hypothyroidism or hyperthyroidism.

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

China · 6 centers

• First Affiliated Hospital of Fujian Medical University — Fuzhou
• Mengchao Hepatobiliary Hospital of Fujian Medical University — Fuzhou
• Fujian Provincial Hospital — Fuzhou
• Zhongshan Hospital of Xiamen University — Xiamen
• First Affiliated Hospital of Xiamen University — Xiamen
• Zhangzhou Affiliated Hospital of Fujian Medical University — Zhangzhou

Identifiers

NCT: NCT06602011 · TALENP002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗