Efficacy and Safety of Sintilimab Combined With Lenvatinib and HAIC for Neoadjuvant Therapy of Borderline Resectable HCC

NCT06904014 | Recruiting Phase 2

• 1 other identifier: SDZLEC2023-110-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-center, randomized controlled exploratory Phase II clinical trial, aiming to assess the efficacy and safety of sintilimab combined with lenvatinib and HAIC for two cycles followed by surgery compared with direct surgery in patients with borderline resectable hepatocellular carcinoma. After signing the informed consent and meeting the inclusion and exclusion criteria, the eligible subjects were randomly divided into the experimental group and the control group:

• Subjects in the experimental group received 200 mg of sintilimab by intravenous infusion on the first day of every 3 weeks. Lenvatinib 8 mg was orally administered once daily, combined with the HAIC-FOLFOX regimen. After two cycles, the patients' conditions were evaluated for surgery.
• Subjects in the control group underwent surgery directly. Both groups of subjects received sintilimab monotherapy as adjuvant treatment for half a year (a total of 8 cycles) after surgery. The treatment was terminated if there was disease recurrence, death, intolerable toxicity, withdrawal of informed consent, initiation of new anti-tumor treatment, or other reasons stipulated in the protocol.

Conditions

HCC

Outcome Measures

Primary Outcomes (1)

• One-year disease-free survival rate

  The 1-year disease-free survival rate (1-year DFS rate) of the experimental group and the control group

  From enrollment to the end of treatment at one year

Secondary Outcomes (3)

• disease-free survival（DFS）

  From enrollment to the end of treatment，assessed up to 3 years

• Overall survival (OS)

  Up to three years

• Pathologic complete response (pCR)

  Up to one year

Study Arms (2)

Experimental：Sintilimab+ Lenvatinib+HAIC+surgery

EXPERIMENTAL

the experimental group received 200 mg of sintilimab by intravenous infusion on the first day of every 3 weeks. Lenvatinib 8 mg was orally administered once daily, combined with the HAIC-FOLFOX regimen. After two cycles, the patients' conditions were evaluated for surgery

Procedure: HAIC; Drug: Sintilimab; Drug: Lenvatinib; Procedure: surgery

Control

OTHER

surgery

Procedure: surgery

Interventions

HAIC PROCEDURE

FOLFOX-hepatic artery infusion

Experimental：Sintilimab+ Lenvatinib+HAIC+surgery

Sintilimab DRUG

200mg, ivgtt, D1, Q3W

Experimental：Sintilimab+ Lenvatinib+HAIC+surgery

Lenvatinib DRUG

8 mg，qd，D1-D21,Q3W

Experimental：Sintilimab+ Lenvatinib+HAIC+surgery

surgery PROCEDURE

surgery

Control; Experimental：Sintilimab+ Lenvatinib+HAIC+surgery

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign a written informed consent before the implementation of any trial-related procedures.
• Male or female, aged ≥18 years and ≤70 years.
• ECOG PS score of 0-2.
• Diagnosed with HCC according to the Diagnosis and Treatment Guidelines for Primary Liver Cancer in China (2019 Edition).
• CNLC stage IIIa, with vascular invasion but no extrahepatic metastasis.
• Child-Pugh score of A/B.
• Portal vein tumor thrombus is classified as type 1-2 according to the Japanese VP classification or type I-II according to the Program classification.
• No previous systemic anti-tumor treatment for hepatocellular carcinoma and eligible for R0 resection.
• Expected survival time \> 3 months.
• At least one measurable lesion according to RECIST 1.1 or mRECIST criteria.
• Adequate organ and bone marrow function, as follows:
• \) Blood routine: absolute neutrophil count (ANC) ≥ 1.5×109/L; platelet count (PLT) ≥ 75×109/L; hemoglobin content (HGB) ≥ 9.0 g/dL.
• \) Liver function: serum total bilirubin (TBIL) ≤ 3×ULN; alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 5×ULN; serum albumin ≥ 28 g/L.
• \) Renal function: serum creatinine (Cr) ≤ 1.5×ULN or clearance of creatinine (CCr) ≥ 50 mL/min (Cockcroft-Gault formula); urine routine test shows urine protein \< 2+; for patients with urine protein ≥ 2+ at baseline, 24-hour urine collection is required and 24-hour urine protein quantification \< 1 g.
• \) Coagulation function: international normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5×ULN.

You may not qualify if:

• Previously histologically/cytologically confirmed liver cancer with components such as fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, etc.
• History of hepatic encephalopathy or liver transplantation.
• Clinical symptoms requiring drainage of pleural effusion, ascites, or pericardial effusion.
• Acute or chronic active hepatitis B or C infection, with HBV DNA \> 2000 IU/ml or 104 copies/ml; HCV RNA \> 103 copies/ml; positive for both hepatitis B surface antigen (HbsAg) and anti-HCV antibody.
• Central nervous system metastasis.
• Esophageal or gastric variceal bleeding events due to portal hypertension within the past 6 months. Known severe (G3) varices on endoscopy within 3 months before the first dose. Evidence of portal hypertension (including splenomegaly on imaging), and high bleeding risk as assessed by the investigator.
• Any life-threatening bleeding events within the past 3 months, including those requiring blood transfusion, surgery or local treatment, or continuous drug treatment.
• Venous or arterial thromboembolic events within the past 6 months, including myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis or any other serious thromboembolic events. Patients with stable thrombosis after conventional anticoagulation treatment, such as those with implanted venous access ports or catheter-related thrombosis, or superficial vein thrombosis, are excluded. Prophylactic use of low-dose low-molecular-weight heparin (e.g., enoxaparin 40 mg/day) is allowed.
• Use of aspirin (\> 325 mg/day) or other known platelet function inhibitors such as dipyridamole or clopidogrel for 10 consecutive days within 2 weeks before the first dose.
• Uncontrolled hypertension, with systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 90 mmHg after optimal medical treatment, or history of hypertensive crisis or hypertensive encephalopathy.
• Symptomatic congestive heart failure (NYHA class II-IV). Symptomatic or poorly controlled arrhythmia. History of congenital long QT syndrome or corrected QTc \> 500 ms (calculated using the Fridericia method) at screening.
• Severe bleeding tendency or coagulation disorders, or currently undergoing thrombolytic therapy.
• History of gastrointestinal perforation and/or fistula within the past 6 months, history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive intestinal resection (partial colectomy or extensive small bowel resection, concurrent with chronic diarrhea), Crohn's disease, ulcerative colitis, or long-term chronic diarrhea.
• History of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, or severe lung function impairment.
• Human immunodeficiency virus (HIV) infection (HIV 1/2 antibody positive), or known syphilis infection.

Sponsors & Collaborators

• Lei ZHAO: lead

Study Sites (1)

Shandong Cancer Hospital and Institute

Jinan, Shandong, China

RECRUITING

MeSH Terms

Interventions

sintilimab; lenvatinib; Surgical Procedures, Operative

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: March 21, 2025
• First Posted: April 1, 2025
• Study Start: October 25, 2023
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2029
• Last Updated: April 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)