Combining Lenvatinib, Tislelizumab, and TACE for Liver Cancer Treatment

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: Study Protocol of a Monocenter, Single-arm, Open Label Clincal Trail

This study is testing a new combination treatment for liver cancer to see if it can help patients at high risk of their cancer coming back after surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Zhejiang Cancer Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, prednisone, Tislelizumab, Lenvatinib
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT05920863 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of a combination treatment involving Lenvatinib, Tislelizumab, and Transarterial Chemoembolization (TACE) as a neoadjuvant regimen for patients with CNLC stage IB and IIA hepatocellular carcinoma who are at high risk for recurrence. The study aims to assess major pathological response and other secondary outcomes such as complete response rates and treatment-related adverse events. By using a single-arm, open-label design, the trial focuses on patients who have not received prior systemic therapies and have specific tumor characteristics that indicate a high risk of recurrence. The goal is to improve surgical outcomes and reduce recurrence rates in liver cancer patients.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with confirmed hepatocellular carcinoma at CNLC stage IB or IIA and specific high-risk factors for recurrence.

Not a fit: Patients who have previously undergone systemic chemotherapy, immunotherapy, or other anti-tumor treatments for hepatocellular carcinoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment approach could significantly reduce the risk of recurrence and improve overall survival rates for patients with hepatocellular carcinoma.

How similar studies have performed: While there have been various combination therapies involving Lenvatinib, the specific approach of combining it with Tislelizumab and TACE as a neoadjuvant treatment is relatively novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Aged 18-75 years old (inclusive);
2. 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;
3. 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.
4. ECOG score of 0 before the first administration of the study drug;
5. Child-Pugh scores is 5-6 points and liver function is grade A;
6. Expected survival time of at least 16 weeks;
7. 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.
8. Male and female participants of childbearing potential must agree to use effective contraception throughout the study period;
9. Sign an informed consent form and agree to provide previously stored tumor tissue specimens or fresh biopsy specimens of the tumor lesion.

Exclusion Criteria:

1. Pathologically diagnosed as non-hepatocellular carcinoma;
2. 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);
3. CNLC stage is IA, IIB or worse.
4. Viral load limited to hepatitis B virus (HBV) DNA\>2000 copies/ml, hepatitis C virus (HCV) RNA\>1000;
5. 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;
6. Significant clinical bleeding or bleeding tendency within 3 months before enrollment or currently undergoing thrombolysis or anticoagulation treatment;
7. Complete intestinal obstruction and incomplete intestinal obstruction requiring treatment, but patients who have had obstruction relieved by fistula or stent placement can be enrolled;
8. 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;
9. 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);
10. 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);
11. Patients undergoing renal replacement therapy;
12. History of other malignant tumors within the past 5 years. Excluding cured basal cell carcinoma or cervical intraepithelial neoplasia;
13. Other patients who are expected to be unable to tolerate surgical treatment;
14. Patients who have had allergic reactions to any component of the study drug;
15. Presence of alcohol dependence, mental illness, pregnancy (or lactation) or other conditions that are not suitable for clinical trials.

Where this trial is running

Hangzhou, Zhejiang

• 1# Banshan East Rd. Zhejiang cancer hospital — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Yuhua Zhang, MD

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