Lenvatinib Combined with Tislelizumab and TACE Applied As Neoadjuvant Regimen for the Patients of CNLC Stage IB and IIA Hepatocellular Carcinoma with High-risk Recurrence Factors

NCT05920863 | Recruiting Phase 2

• 1 other identifier: 20230408
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This is a monocenter, single-arm, open-label study to evaluate the efficacy and safety of Lenvatinib combined with Tislelizumab and TACE applied as neoadjuvant regimen for the patients of CNLC stage IB and IIA hepatocellular carcinoma with high risk of recurrence Primary outcome: Major pathological response (MPR) Secondary outcomes: pathological complete response (pCR), R0 resection rate, objective response rate (ORR), disease control rate (DCR), treatment-related adverse events (TRAE)

Conditions

Hepatocellular Carcinoma; Lenvatinib; Tislelizumab; TACE; Pharmorubicin; Oxaliplatin

Outcome Measures

Primary Outcomes (1)

• Major pathological response

  Proportion of residual tumor ingredient lesser than 30% in the postoperative pathological result.

  Up to 16 weeks

Secondary Outcomes (6)

• Pathological complete response

  Up to 16 weeks

• R0 resection rate

  Up to 16 weeks

• Objective response rate (ORR)

  Up to 4 cycle treatment (each cycle is 4 weeks), an average of 16 weeks.

• disease control rate (DCR)

  Up to 4 cycle treatment (each cycle is 4 weeks), an average of 16 weeks.

• treatment-related adverse events (TRAE)

  Up to 4 cycle treatment (each cycle is 4 weeks), an average of 16 weeks.

Study Arms (1)

Experimental

EXPERIMENTAL

1. TACE: pharmorubicin 30mg, oxaliplatin 50mg, cycle 4-5 week. 2. Tislelizumab: 200mg, cycle 3 week. 3. Lenvatinib: weight \<60kg, 8mg/day; weight ≥60kg, 12mg/day.

Procedure: TACE; Drug: Tislelizumab, Lenvatinib

Interventions

TACE PROCEDURE

TACE: pharmorubicin 30mg, oxaliplatin 50mg, cycle 4-5 week.

Experimental

Tislelizumab, Lenvatinib DRUG

Tislelizumab: 200mg, cycle 3 week. Lenvatinib: weight \<60kg, 8mg/day; weight ≥60kg, 12mg/day.

Experimental

Eligibility Criteria

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

You may qualify if:

• Aged 18-75 years old (inclusive);
• HCC is confirmed by preoperative pathological examination or meet the criterion of diagnosis and treatment norms of primary HCC issued by health commission, PRC. No prior systemic chemotherapy, immunotherapy, targeted therapy, or other anti-tumor treatments for HCC;
• Patients with CNLC IB or IIA stage tumors before surgery and meeting the following conditions: radiological evaluation shows narrow or none surgical margins, and preoperative tumor markers AFP+PIVKA is greater than 1600.
• ECOG score of 0 before the first administration of the study drug;
• Child-Pugh scores is 5-6 points and liver function is grade A;
• Expected survival time of at least 16 weeks;
• Pre-administration organ function levels meet the requirements and are tolerant of surgery. The functional indicators of important organs meet the following requirements: hemoglobin ≥90g/L, neutrophil count ≥1.5×10⁹/L, platelet count ≥100×10⁹/L; aspartate aminotransferase or alanine aminotransferase ≤5 times the upper limit of normal (ULN), alkaline phosphatase ≤2.5 ULN, serum albumin ≥30g/L; serum creatinine \<1.5 ULN; international normalized ratio (INR) ≤2 or prothrombin time (PT) within the upper limit of normal range ≤6 seconds; serum creatinine ≤1.5 ULN, creatinine clearance rate ≥60 mL/min.
• Male and female participants of childbearing potential must agree to use effective contraception throughout the study period;
• Sign an informed consent form and agree to provide previously stored tumor tissue specimens or fresh biopsy specimens of the tumor lesion.

You may not qualify if:

• Pathologically diagnosed as non-hepatocellular carcinoma;
• Previously received anti-tumor treatments such as chemotherapy, radiotherapy, radiofrequency ablation, intervention, targeted therapy, immunotherapy or surgical treatment for liver cancer (excluding previous non-tumor-related surgery or diagnostic biopsy);
• CNLC stage is IA, IIB or worse.
• Viral load limited to hepatitis B virus (HBV) DNA\>2000 copies/ml, hepatitis C virus (HCV) RNA\>1000;
• Long-term steroid users who require long-term systemic steroid therapy (equivalent to \>10 mg of prednisone per day) or any other form of immunosuppressive treatment;
• Significant clinical bleeding or bleeding tendency within 3 months before enrollment or currently undergoing thrombolysis or anticoagulation treatment;
• Complete intestinal obstruction and incomplete intestinal obstruction requiring treatment, but patients who have had obstruction relieved by fistula or stent placement can be enrolled;
• Active severe clinical infection (\> grade 2, NCI-CTCAE version 5.0), including active tuberculosis; history of active tuberculosis infection for more than 1 year before enrollment, not treated with regular anti-tuberculosis treatment or tuberculosis still in the active period; active known or suspected autoimmune disease;
• Uncontrolled diabetes (fasting blood glucose ≥10 mmol/L), severe lung disease (such as acute pulmonary disease, pulmonary fibrosis that affects lung function, interstitial lung disease. Excluding recovered radiation pneumonitis);
• Clinically significant cardiovascular disease; hypertension which cannot be well controlled by anti-hypertensive drugs (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);
• Patients undergoing renal replacement therapy;
• History of other malignant tumors within the past 5 years. Excluding cured basal cell carcinoma or cervical intraepithelial neoplasia;
• Other patients who are expected to be unable to tolerate surgical treatment;
• Patients who have had allergic reactions to any component of the study drug;
• Presence of alcohol dependence, mental illness, pregnancy (or lactation) or other conditions that are not suitable for clinical trials.

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead

Study Sites (1)

1# Banshan East Rd. Zhejiang cancer hospital

Hangzhou, Zhejiang, 310022, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

tislelizumab; lenvatinib

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

Central Study Contacts

Yuhua Zhang, MD

CONTACT

+86-0571-88128058; drzhangyuhua@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Prior to enrollment in the study, doctors asked and recorded the patient's medical history, and if eligible participants volunteered to participate in the study, they would sign informed consent.If they are not willing to participate in the study, we will do the usual treatment
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice director of Hepatobiliary and Pancreatic Surgery (Chair)

Model Details: This is a prospective, single-arm, open phase II clinical study

Study Record Dates

• First Submitted: June 17, 2023
• First Posted: June 27, 2023
• Study Start: July 1, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: February 11, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)