The Safety and Efficacy of Transarterial Chemoembolization (TACE) + Lenvatinib + Programmed Cell Death Protein 1 (PD-1) Antibody of Advanced Unresectable Hepatocellular Carcinoma

NCT04997850 | Completed Phase 1

• 1 other identifier: 311576
• Study Type: interventional
• Target: 142
• Locations: 1 country
• Sites: 1

Brief Summary

We adopted the prospective cohort study to compare the safety and efficacy of Transarterial Chemoembolization (TACE) + Lenvatinib + Programmed Cell Death Protein 1 (PD-1) Antibody in the treatment of advanced unresectable liver cancer.The purposes of our study include：1. Primary objective: To compare the safety and efficacy of TACE combined with Lenvatinib and PD-1 antibody versus TACE alone in the conversion-resection of patients with advanced unresectable hepatocellular carcinoma.2. Secondary objective: To compare the long-term outcome of TACE combined with Lenvatinib and PD-1 antibody versus TACE alone for patients with advanced unresectable hepatocellular carcinoma.

Conditions

Hepatocellular Carcinoma Non-resectable; Transarterial Chemoembolization; Tyrosine Kinase Inhibitor; Immune Checkpoint Blockade

Keywords

Hepatocellular Carcinoma Non-resectable; transarterial chemoembolization; tyrosine kinase inhibitor; immune checkpoint blockade

Outcome Measures

Primary Outcomes (1)

• Conversion resection rate

  ratio of conversion resection patients / enrolled patients

  48 weeks

Secondary Outcomes (3)

• Objective Response Rate

  48 weeks

• PFS

  96 weeks

• OS

  96 weeks

Study Arms (2)

TACE + lenvastinib + sindilimab/carrelizumab

EXPERIMENTAL

The patients with body weight ≥ 60kg were treated with oral lenvastinib within 3 days (the initial dose was 12mg QD for patients with body weight \< 60kg, the initial dose was 8mg QD for patients with body weight \< 60kg). After 1-2 weeks of treatment, the patients received the first TACE treatment (3 days before TACE), and continued to take oral lunvastinib 3 days after TACE. Within one week after TACE treatment, 200 mg of sindilimab was given intravenously once every three weeks (every 21 days as a cycle) or 200 mg of carrelizumab was given intravenously once every three weeks (every 21 days as a cycle).

Drug: lenvatinib + sindilimab/carrelizumab; Procedure: TACE

TACE

ACTIVE COMPARATOR

TACE treatment is strictly in accordance with the Chinese guidelines for clinical practice of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (2018 Edition). The patients with HCC were selected according to the inclusion criteria (referring to the conditions of the subjects). The subjects who met the inclusion criteria could enter the study after they signed the informed consent. 4-6 weeks after the first TACE treatment, the resectability criteria were evaluated. If not, the next cycle of TACE treatment was carried out. The general principle is to reduce the number of interventional treatment and extend the interval of interventional operation as far as possible under the condition of controlling the tumor and the survival of patients with tumor.

Procedure: TACE

Interventions

lenvatinib + sindilimab/carrelizumab DRUG

4-6 weeks after the first TACE treatment, the resectability criteria were evaluated. If not, the next treatment cycle was carried out. The trial was terminated if the drug was stopped for more than 28 days due to adverse drug reactions or other reasons. Patients with PD after 6 cycles of sindilimab/carrelizumab treatment were terminated. The follow-up treatment was based on the principle of individualization, multidisciplinary discussion and patients' willingness.

TACE + lenvastinib + sindilimab/carrelizumab

TACE PROCEDURE

TACE treatment is strictly in accordance with the Chinese guidelines for clinical practice of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (2018 Edition). The patients with HCC were selected according to the inclusion criteria (referring to the conditions of the subjects). The subjects who met the inclusion criteria could enter the study after they signed the informed consent. 4-6 weeks after the first TACE treatment, the resectability criteria were evaluated. If not, the next cycle of TACE treatment was carried out. The general principle is to reduce the number of interventional treatment and extend the interval of interventional operation as far as possible under the condition of controlling the tumor and the survival of patients with tumor.

TACE; TACE + lenvastinib + sindilimab/carrelizumab

Eligibility Criteria

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

You may qualify if:

• (1) 18 years old ≤ age ≤ 70 years old, no gender limit; (2) HCC patients who are in strict compliance with the clinical diagnostic criteria of the "Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition) or confirmed by histopathology or cytology; (3) Have not received any systemic treatment for HCC in the past. (4) ECOG PS score 0-1; (5) Child-Pugh liver function rating AB; (6) Patients with BCLC stage B and C liver cancer; or stage A patients without sufficient remaining liver volume (no cirrhosis liver: SFLVR\<30%; cirrhosis liver: SFLVR\<40%); (7) According to the evaluation criteria for the efficacy of solid tumors (mRECIST), there is at least one imaging measurable lesion; (8) If the patient is HBsAg positive, HBV-DNA will be less than 2000 IU/ml (10000 copies/ml) during PD-1antibody treatment; (9) The function of major organs is normal, that is, it meets the following standards:
• Sufficient bone marrow function, defined as: Absolute neutrophil count (ANC greater than or equal to 1.5×10\^9 per liter (/L); hemoglobin (Hb greater than or equal to 8.5 grams per deciliter (g/dL); platelet count greater than or equal to 75×10\^9/L).
• Sufficient liver function, defined as: Aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) are less than or equal to 5 ULN.
• Sufficient coagulation function, defined as the International Normalized Ratio (INR) less than or equal to 2.3.
• Sufficient renal function is defined as a creatinine clearance rate greater than 40 milliliters per minute (mL/min), calculated according to Cockcroft and Gault formulas.
• Sufficient pancreatic function, defined as amylase and lipase≤1.5×ULN.
• Normal thyroid function is defined as thyroid stimulating hormone (TSH) within the normal range. If the baseline TSH is outside the normal range, subjects whose total T3 (or FT3) and FT4 are within the normal range can also be included in the group; (10) Use up to 3 antihypertensive drugs to adequately control blood pressure (BP), defined as BP \<= 150/90 mmHg at the time of screening, and there is no change in antihypertensive treatment within 1 week before cycle 1/day 1. .
• (11) The patient is expected to survive more than 3 months. (12) No pregnancy or pregnancy plans. (13) The subjects voluntarily joined the study and signed an informed consent form, with good compliance and cooperation with follow-up.

You may not qualify if:

• (1) Extrahepatic metastasis of primary liver cancer; (2) Diffuse liver cancer, intrahepatic tumor burden ≥50%; portal vein tumor thrombus (superior mesenteric vein tumor thrombus, type IV), inferior vena cava tumor thrombus; (3) Contraindications of TACE and epirubicin; (4) Those who have participated in other clinical trial drugs within 4 weeks; (5) Those who are known to be allergic to the ingredients of lenvatinib; (6) Those who are known to be allergic to the active ingredients or excipients of Sintilizumab; (7) A history of liver resection, liver transplantation, interventional therapy, and other malignant tumors; (8) Women who are pregnant or breast-feeding; those with fertility who are unwilling or unable to take effective contraceptive measures; (9) Patients with grade II or higher myocardial ischemia or myocardial infarction, poorly controlled arrhythmia (including QTc interval ≥470 ms); according to NYHA standards, grade III to IV cardiac insufficiency, or cardiac color Doppler ultrasound examination suggests left ventricular ejaculation Blood score LVEF\<50%; (10) Abnormal coagulation function (INR\>1.5 or prothrombin time (PT)\>ULN+4 seconds or APTT\>1.5 ULN), have bleeding tendency or are receiving thrombolytic or anticoagulant therapy; (11) Have a mental illness or a history of psychotropic drug abuse; (12) Combined with HIV-infected patients; (13) Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation; (14) Patients with active infection; (15) Patients with poor compliance such as floating population; (16) Have received the following therapies in the past: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or for another stimulating or synergistic inhibition of T cell receptors (for example, CTLA-4, OX-40, CD137) medicine; (17) An active autoimmune disease that requires systemic treatment (such as the use of disease-relieving drugs, glucocorticoids, or immunosuppressive agents) occurred within 2 years before the first administration. Replacement therapies (such as thyroxine, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency, etc.) are not considered systemic treatments; (18) Are receiving systemic glucocorticoid therapy (excluding nasal spray, inhalation or other local glucocorticoids) or any other form of immunosuppressive therapy within 7 days before the first administration of the study; Note: physiological doses are allowed Glucocorticoids (≤10 mg/day prednisone or equivalent); (19) There is clinically uncontrollable pleural effusion/abdominal effusion (patients who do not need to drain the effusion or stop drainage for 3 days without a significant increase in effusion can be included in the group); (20) Acute or chronic active hepatitis B or C infection, HBV DNA ≥ 200000IU/ml or 106 copies/ml when Sintilimab is treated; hepatitis C virus HCV RNA ≥ 103 copies/ml; Hepatitis B surface anti-(HbsAg) and anti-HCV antibodies are positive at the same time.
• (21) Live vaccine has been vaccinated within 30 days before the first dose (cycle 1, day 1); Note: It is allowed to receive the inactivated virus vaccine for seasonal influenza injection within 30 days before the first dose; but it is not allowed to receive intranasal vaccine Medicated live attenuated influenza vaccine.

Sponsors & Collaborators

• Xinrui Zhu，MD: lead

Study Sites (1)

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

Location

MeSH Terms

Interventions

lenvatinib; camrelizumab

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: attending doctor

Study Record Dates

• First Submitted: March 17, 2021
• First Posted: August 10, 2021
• Study Start: October 1, 2020
• Primary Completion: May 24, 2022
• Study Completion: January 31, 2024
• Last Updated: August 29, 2025

Record last verified: 2025-08

Locations

CN (1)