MedTrace Logo

Assessment of the Efficacy of Lenvatinib Versus Sorafenib in the Management of Advanced Hepatocellular Carcinoma

NCT05391867 · Status: UNKNOWN · Phase: NA · Type: INTERVENTIONAL · Enrollment: 70

Last updated 2022-05-26

No results posted yet for this study

Summary

Hepatocellular carcinoma is the most common type of liver cancer, which is the 3rd leading cause of cancer deaths worldwide. The incidence is expected to increase as a consequence of chronic liver disease with its multiple risk factors, including chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, excessive alcohol consumption, nonalcoholic fatty liver disease, hemochromatosis, and aflatoxin B1.It is estimated that 70%-90% of patients with HCC have chronic liver disease and cirrhosis, which limits the feasibility of surgical procedures in advanced cases. There are limited treatment options for HCC patients who are ineligible for surgical resection. Locoregional therapies, such as radiofrequency ablation, transarterial chemoembolization (TACE), transarterial embolization (TAE), or hepatic arterial infusion chemotherapy (HAIC), are primarily recommended, and if one of those fail, then systemic therapy is considered. The 2013 Japan Society of Hepatology HCC Guidelines outlined that the factors influencing treatment decisions should be based on the degree of liver damage (Child-Pugh), presence or absence of extrahepatic spread and macrovascular invasion, the number of tumors, and tumor diameter. Sorafenib has been the standard of care since 2007, when the SHARP trial demonstrated that sorafenib improved median overall survival (OS) compared to placebo in patients who had not received prior systemic therapy (10.7 vs 7.9 months, HR =0.69, P\<0.001). In patients from the Asia-Pacific region taking sorafenib, the median improvement in overall survival compared with placebo was 2.3 months (6.5 months vs 4.2 months; HR 0.68; p=0.014). Drug development for hepatocellular carcinoma in the past 10 years has been marked by four failed global phase 3 trials (of sunitinib, brivanib, linifanib, and erlotinib plus sorafenib) that did not show non-inferiority. Sorafenib, an oral multikinase inhibitor, has been the only systemic therapy demonstrated to extend overall survibility as a firstline treatment, showing a median improvement of 2.8 months compared with placebo (10.7 months vs. 7.9 months; hazard ratio \[HR\] 0.69; p\\0.001).6 Inpatients from the Asia-Pacific region taking sorafenib, the median OS (mOS) improvement compared with placebo was 2.3 months (HR 0.68; p = 0.014). The use of other molecularly targeted agents has not demonstrated efficacy via non-inferiority or superiority to sorafenib; thus, until the appearance of lenvatinib, sorafenib has also been widely used as the first-line treatment for uHCC patients in Japan. Recently, regorafenib and Nivolumab were approved as a second-line systemic treatment for patients who do not respond to the first-line treatments. Otherwise, best supportive care or participation in clinical trials is recommended in the second-line setting by treatment guidelines. Chemotherapy in combination with sorafenib (doxorubicin) and radioembolization with SIR Spheres Y-90 resin microspheres failed to demonstrate a survival benefit or showed a worse safety profile compared to sorafenib in the first-line setting. Eventually, the PhaseIII non-inferiority REFLECT trial showed that lenvatinib was non-inferior compared to sorafenib.

Conditions

Interventions

DRUG

Lenvatinib

Tyrosine kinase inhibitor

Sponsors & Collaborators

  • Sir Salimullah Medical College Mitford Hospital

    lead OTHER_GOV

Principal Investigators

  • Mohammad S Hossain, MBBS, MD · Sir Salimullah Medical College

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Max Age
65 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2022-01-01
Primary Completion
2022-12-31
Completion
2023-06-30

Countries

  • Bangladesh

Study Locations

More Related Trials

Entities

Drugs
Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05391867 on ClinicalTrials.gov