TACE Combined With Lenvatinib Versus TACE Sequential Lenvatinib in the Treatment of Intermediate/Advanced Liver Cancer

NCT05220020 | Unknown Phase 3

• 1 other identifier: B2021-370-01
• Study Type: interventional
• Target: 299
• Locations: 1 country
• Sites: 1

Brief Summary

TACE(transcatheter arterial chemoembolization) has been recommended by domestic and international guidelines as the standard treatment for a subset of HCC patients with very high heterogeneity, including BCLC stage B(intermediate-stage) and some BCLC stage C(advanced-stage). However, for these patients, TACE therapy alone is often difficult to achieve satisfactory efficacy. Moreover, in the course of repeated TACE treatment, tumor remission rate continues to decrease, and drug resistance and liver function damage are prone to be aggravated.Studies have shown that TACE and TKI combined therapy can not only inhibit the release of VEGF and other angiogenic growth factors after TACE, but also prolong the interval of TACE treatment、reduce the frequency of TACE treatment by inhibiting residual tumor proliferation, thus reducing liver function damage.Lenvatinib therapy,which is associated with a high response rate compared with Sorafinib and the cost-effect advantage of Lenvatinib was significantly better than that of sorafenib.But it has not been determined whether lenvatinib should be used synchronously or sequentially based on TACE.Through the comparative study of different timing combinations, we explore the interventional timing of Lenvatinib in intermediate-advanced liver cancer, providing a new scheme for interventional combination therapy.

Conditions

Hepatocellular Carcinoma

Keywords

TACE; Lenvatinib; Hepatocellular carcinoma

Outcome Measures

Primary Outcomes (1)

• Two-Years Overall Survival Rate

  Percentage of patients who survived two years after inclusion

  Two-Years

Secondary Outcomes (5)

• Two-years progression-free survival rate

  Two-years

• Objective response rate

  Two-years

• Evaluate the patients cancer-related QoL using the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaire (QLQ), the EORTC QLQ-HCC18.

  From date of randomization up to two years, approximately

• Progressive survival to TACE intolerance(TTUP，time to TACE-untreatable progression)

  From date of randomization up to two years, approximately

• Evaluate the patients cancer-related QoL using the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaire (QLQ), the EORTC QLQ-C30.

  From date of randomization up to two years, approximately

Study Arms (2)

Experimental group

EXPERIMENTAL

Synchronous treatment group: the first course of TACE treatment was started after 2-3 weeks Lenvatinib treatment.

Procedure: TACE(Transcatheter arterial chemoembolization); Drug: Lenvatinib

Control group

ACTIVE COMPARATOR

Sequential treatment group: patients with uncontrolled TACE progression after TACE treatment were sequentially treated with Lenvatinib.

Procedure: TACE(Transcatheter arterial chemoembolization); Drug: Lenvatinib

Interventions

TACE(Transcatheter arterial chemoembolization) PROCEDURE

Hepatic arterial chemoembolization treatment

Control group; Experimental group

Lenvatinib DRUG

Experimental group(Synchronous treatment group): the first course of TACE treatment was started after 2-3 weeks Lenvatinib treatment.Control group:(Sequential treatment group)patients with uncontrolled TACE progression after TACE treatment were sequentially treated with Lenvatinib.

Also known as: Lenvatinib oral

Control group; Experimental 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:

• Provision of signed and dated, written informed consent form (ICF) and any locally required authorization obtained from the patient prior to any mandatory study specific procedures, sampling, and analyses.
• Provision of signed and dated written genetic informed consent prior to optional collection of sample for genetic analysis.
• Patients with BCLC stage C hepatocellular carcinoma confirmed by pathology or clinically diagnosed
• Anticipated life expectancy ≥ 12 months
• Eligible for TACE treatment, including BCLC-B, and BCLC-C only for Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• No prior systemic therapy (including systemic investigational agents) for HCC, especially immunotherapy
• Age ≥18 years and \< 75 years at the time of screening.
• Portal vein invasion or extrahepatic oligosaccharides were detected by baseline imaging. Oligosaccharides were defined as no more than two extrahepatic organs and no more than three tumors.
• Portal vein thrombosis visible on baseline/eligibility imaging, patients with Vp1 and Vp2 are included
• Patients who have previously undergone surgical resection, thermal ablation and other radical therapies for liver cancer may be enrolled. Prior TACE therapy must be used as part of the radical therapy (e.g. in combination with thermal ablation or surgery), but not as the sole form of previous treatment. These treatments need to be completed one month before enrollment.
• Child-Pugh score class A to B7
• No local antitumor therapy for hepatocellular carcinoma was received within 4 weeks prior to enrollment
• No evidence of extrahepatic disease on any available imaging
• No previous systemic antitumor therapy for hepatocellular carcinoma
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment

You may not qualify if:

• Evidence of macrovascular invasion (MVI).
• Evidence of extrahepatic spread (EHS)
• Being a candidate for curative treatments (e.g. surgical resection, RFA or liver transplantation).
• Any condition representing a contraindication to TACE as determined by the investigators(for example, the main portal vein obstruction without collateral vessels formed, etc.);
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC;History of leptomeningeal disease;
• Allergy to TACE process medications (such as contrast agents) or to Lenvatinib is known or suspected
• There are obvious arteriovenous fistula or portal vein fistula in the liver.
• Tumor invasion or oppression of the common bile duct, resulting in malignant obstructive jaundice;
• Tumor volume of 70% or more of the liver;
• Previous history of molecular targeted therapy, such as sorafenib, apatinib, etc.
• Patients who had previously used systemic therapy (e.g., immunotherapy, targeted therapy) were excluded from the study
• Severe heart conditions, such as congestive heart failure \& GT; New York Heart Association (NYHA) Class II, active coronary artery disease (patients with myocardial infarction that occurred 6 months prior to enrollment), arrhythmias requiring treatment (other than beta-blockers, calcium antagonists, or digoxin); Uncontrolled hypertension (diastolic blood pressure not below 90mmHg even after treatment with 3 antihypertensive drugs;
• Active clinical severe infection (\> Level 2 NCI-CTCAE version 4.0);
• Presence of active pulmonary tuberculosis or inability to exclude intrapulmonary lesions of old pulmonary tuberculosis.
• Known tumors of the central nervous system, including brain metastases;

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Department of Minimally Invasive and Interventional Radiology, Liver Cancer Study and Service Group, Sun Yat-sen University Cancer Center,

Guangzhou, Guangdong, 500060, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

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

Study Officials

• Ming Zhao, M.D. & Ph.D.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ming Zhao, M.D. & Ph.D.

CONTACT

86-20-87343272; zhaoming@sysucc.org.cn

Ning Lv, M.D. & Ph.D.

CONTACT

86-20-87343272; lvning@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Director of Minimally Invasive Intervention

Study Record Dates

• First Submitted: January 12, 2022
• First Posted: February 2, 2022
• Study Start: May 18, 2022
• Primary Completion: February 28, 2024
• Study Completion: February 28, 2025
• Last Updated: May 19, 2022

Record last verified: 2022-05

Locations

CN (1)