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A phase 3 study of lenvatinib (E7080) in subjects with unresectable hepatocellular carcinoma

Phase 3
Completed
Conditions
Hepatocellular carcinoma
Registration Number
JPRN-jRCT2080222067
Lead Sponsor
Eisai Co., Ltd.
Brief Summary

This study is a positive study that met its primary endpoint showing that OS with lenvatinib was non-inferior to sorafenib. Lenvatinib also demonstrated statistically significant and clinically meaningful improvement for all secondary efficacy endpoints (PFS, TTP and ORR). Lenvatinib has an acceptable safety profile when treatment is initiated at 8 mg or 12 mg QD (based on body weight) and adjusted by a dose-titration algorithm to manage toxicity.

Detailed Description

Not available

Recruitment & Eligibility

Status
completed
Sex
All
Target Recruitment
954
Inclusion Criteria

1. Subjects must have confirmed diagnosis of unresectable HCC,
2. At least 1 measurable target lesion,
3. Subjects categorized to stage B (not applicable for transarterial chemoembolization [TACE] stage C based on Barcelona Clinic Liver Cncer (BCLC) staging system,
4. Adquate bone marrow function,
5. Adequate liver function,
6. Adquate blood coagulation function,
7. Adequately controlled blood pressure (BP) with 0 or 1 antihypertensive medications,
8. Child-Pugh score A,
9. ECOG-PS 0 or 1,
10. Survival expectation of 12 weeks or longer after starting study drug,
11. Males or females aged at least 18 years (or any age greater than 18 years as determined by country legislation) at the time of informed consent

Exclusion Criteria

1.Imaging findings for HCC corresponding to any of the following:
HCC with at least 50% liver occupation
Clear invasion into the bile duct
Portal vein invasion at the main portal branch (Vp4)
2.Subjects who have received any systemic chemotherapy, including sorafenib, or any systemic investigational anticancer agents, including lenvatinib, for advanced/unresectable HCC. Note: Subjects who have received local hepatic injection chemotherapy are eligible.
3.Subjects who have received any anticancer therapy (including surgery, percutaneous ethanol injection, radio frequency ablation, transarterial [chemo] embolization, hepatic intra-arterial chemotherapy, biological, immunotherapy, hormonal, or radiotherapy) or any blood enhancing treatment (including blood transfusion, blood products, or agents that stimulate blood cell production, e.g., G-CSF) within 28 days prior to randomization
4.Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib in the opinion of the investigator
5.Bleeding or thrombotic disorders or use of anticoagulants such as, warfarin or similar agents requiring therapeutic INR monitoring. (Treatment with low molecular weight heparin is allowed.)
6.Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least 1/2 of teaspoon) within 28 days prior to randomization
7.Gastric or esophageal varices that require treatment
8.Meningeal carcinomatosis
9.Subjects having at least 2+ proteinuria on urine dipstick testing will undergo 24 h urine collection for quantitative assessment of proteinuria. Subjects with urine protein of at least 1 g/24 h will be ineligible.
10.Arterial-portal venous shunt or arterial-venous shunt preventing proper diagnosis of tumor
11.Any medical or other condition that in the opinion of the investigator would preclude the subject's participation in a clinical study
12.Any history of drug or alcohol dependency or abuse within the prior 2 years
13.Major surgery within 3 weeks prior to randomization or scheduled for surgery during the study
14.Subject has had a liver transplant

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
efficacy<br>Overall survival
Secondary Outcome Measures
NameTimeMethod
safety<br>Progression-free survival
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