A Clinical Study of Tislelizumab Combined With TACE and Lenvatinib in the Neoadjuvant Treatment of Resectable HCC

NCT06003673 | Unknown Phase 4

• 1 other identifier: MRCTA.ECFAH of FMU[2023]405
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

In order to improve the R0 resection rate, reduce distant metastasis, and lower postoperative recurrence, there is a growing exploration of surgical treatments for hepatocellular carcinoma (HCC), including preoperative neoadjuvant therapy and postoperative adjuvant therapy. This study is a single-arm, prospective, exploratory clinical trial aimed at evaluating the effectiveness and safety of combining tislelizumab with transarterial chemoembolization (TACE) and lenvatinib as neoadjuvant therapy for resectable CNLC stage IIa-IIb HCC patients. The primary research endpoint of this study is recurrence-free survival (RFS). A total of 20 Chinese HCC patients with stage IIa-IIb and tumors deemed resectable by the investigator are enrolled in this study. For stage IIa patients, the inclusion criteria require meeting any of the following: unclear tumor boundaries, proximity to blood vessels, or suspicious residual margins. The enrolled patients undergo 2 cycles of neoadjuvant therapy, with each cycle consisting of treatment every 3 weeks. On the first day of the first treatment cycle, conventional transarterial chemoembolization (TACE) is performed, and concomitant intravenous infusion of tislelizumab at a dose of 200mg is given, followed by oral administration of lenvatinib at a dose of 8/12mg once daily. On the first day of the second cycle, tislelizumab is again administered intravenously at a dose of 200mg, TACE is not repeated, and lenvatinib treatment is continued. Within 2-4 weeks after the completion of neoadjuvant therapy, the investigator evaluates the tumor's suitability for surgical resection based on comprehensive assessment of imaging results. Subsequently, tumor resection surgery is performed on eligible patients, followed by survival and safety follow-up for the patients.

Conditions

Hepatocellular Carcinoma Resectable

Keywords

hepatocellular carcinoma; resectable; CNLC stage IIa-IIb; neoadjuvant therapy; Tislelizumab; Lenvatinib; Transarterial Chemoembolization (TACE)

Outcome Measures

Primary Outcomes (1)

• recurrence-free survival (RFS)

  The period of time from the first day of curative surgery until tumor recurrence or death from any cause.

  up to 36 months

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  10 weeks

• Pathological Complete Response Rate (pCR)

  10 weeks

• Major Pathological Response Rate (MPR)

  10 weeks

• R0 Resection Rate

  10 weeks

• Overall Survival (OS)

  up to 36 months

Study Arms (1)

Neoadjuvant therapy group

EXPERIMENTAL

Participants will receive a combination treatment of Tislelizumab, Lenvatinib, and Transarterial Chemoembolization (TACE).

Combination Product: neoadjuvant therapy

Interventions

neoadjuvant therapy COMBINATION_PRODUCT

The enrolled patients undergo 2 cycles of neoadjuvant therapy, with each cycle consisting of treatment every 3 weeks. On the first day of the first treatment cycle, conventional transarterial chemoembolization (TACE) is performed, and concomitant intravenous infusion of tislelizumab at a dose of 200mg is given, followed by oral administration of lenvatinib at a dose of 8/12mg once daily. On the first day of the second cycle, tislelizumab is again administered intravenously at a dose of 200mg, TACE is not repeated, and lenvatinib treatment is continued. Within 2-4 weeks after the completion of neoadjuvant therapy, the investigator evaluates the tumor's suitability for surgical resection based on a comprehensive assessment of imaging results. Subsequently, eligible patients undergo tumor resection surgery, followed by follow-up for survival and safety monitoring.

Neoadjuvant therapy group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must voluntarily enroll in this study and provide signed informed consent.
• Male or female patients between the ages of 18 and 75 years old.
• Patients diagnosed with hepatocellular carcinoma (HCC) confirmed by histopathology or imaging.
• Chinese liver cancer staging of IIa-IIb with hepatocellular carcinoma considered resectable by the investigator. For IIa-stage patients, they must meet at least one of the following criteria: unclear tumor margins, proximity to blood vessels, or suspicious residual margins.
• At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) guidelines (measurable lesions with CT scan long diameter ≥ 10 mm or lymph node lesions with CT scan short diameter ≥ 15 mm, and no prior local treatment such as radiation or cryotherapy).
• Child-Pugh liver function class A.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• No prior systemic treatment for HCC.
• For HBsAg-positive patients, HBV-DNA \< 200,000 IU/ml (106 copies/ml), and receiving routine antiviral therapy.
• Expected survival of at least 3 months.
• Normal major organ function, meeting the following criteria:
• Hematology criteria:
• Hemoglobin (HB) ≥ 90 g/L;
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1500/m3);
• Platelet count (PLT) ≥ 75 × 109/L.

You may not qualify if:

• Extrahepatic metastasis of primary liver cancer.
• Diffuse liver cancer with tumor burden ≥ 50% of liver volume; and/or macrovascular invasion of the portal vein classified as Type IV; and/or inferior vena cava tumor thrombosis.
• Prior treatment with targeted immunotherapy agents, including but not limited to anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) antibodies.
• Contraindications for Transarterial Chemoembolization (TACE) treatment.
• Participation in other investigational drug trials within the past 4 weeks.
• Medical history and comorbidities:1)Active, known, or suspected autoimmune diseases, including a history of allogeneic organ transplantation, allogeneic hematopoietic stem cell transplantation, HIV positive history, or acquired immunodeficiency syndrome (AIDS) history. 2)Severe cardiovascular diseases: Grade II or higher myocardial ischemia or myocardial infarction, poorly controlled arrhythmia; NYHA Class III-IV heart failure, or left ventricular ejection fraction (LVEF) \< 50% based on echocardiography. 3)Active infections. 4)Known allergies to components of Tislelizumab or Lenvatinib. 5)History of substance abuse, alcoholism, or drug addiction.
• Ineligibility as determined by the investigator.

Sponsors & Collaborators

• First Affiliated Hospital of Fujian Medical University: lead

Study Sites (1)

The First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, 350000, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Study Officials

• Zhang Zhibo, PhD

  First Affiliated Hospital of Fujian Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhang Zhibo, PhD

CONTACT

008618559853003; wql0211@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Hepatobiliary and Pancreatic Surgery Department

Study Record Dates

• First Submitted: August 14, 2023
• First Posted: August 22, 2023
• Study Start: July 1, 2023
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2025
• Last Updated: October 24, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)