A Multicenter, Open-Label, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib (E7080) Versus Sorafenib in First-line Treatment of Participants With Unresectable Hepatocellular Carcinoma
A Multicenter, Randomized, Open-Label, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib (E7080) Versus Sorafenib in First-Line Treatment of Subjects With Unresectable Hepatocellular Carcinoma
2 other identifiers
interventional
954
21 countries
186
Brief Summary
E7080-G000-304 is a multicenter, randomized, open-label, noninferiority Phase 3 study to compare the efficacy and safety of lenvatinib versus sorafenib as a first-line systemic treatment in participants with unresectable Hepatocellular Carcinoma (HCC).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Mar 2013
Longer than P75 for phase_3
186 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 2, 2013
CompletedFirst Posted
Study publicly available on registry
January 4, 2013
CompletedStudy Start
First participant enrolled
March 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 13, 2016
CompletedResults Posted
Study results publicly available
September 25, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
March 10, 2021
CompletedApril 5, 2022
March 1, 2022
3.7 years
January 2, 2013
August 27, 2018
March 8, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Survival (OS)
OS was defined as the duration from the date of randomization until the date of death from any cause. Participants who were lost to follow-up were censored at the last date the participant was known to be alive, and participants who remained alive were censored at the time of data cutoff.
From date of randomization until date of death from any cause (approximately up to 3.8 years)
Secondary Outcomes (7)
Progression Free Survival (PFS)
From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (approximately up to 3.8 years)
Time to Progression (TTP)
The time from the date of randomization to the date of first documentation of disease progression (approximately up to 3.8 years)
Objective Response Rate (ORR)
From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (approximately up to 3.8 years)
Time to Clinically Meaningful Worsening of Health Related Quality of Life (HRQoL) Assessed Using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
Baseline up to Off-Treatment Visit (approximately up to 3.8 years)
Time to Clinically Meaningful Worsening of HRQoL Assessed Using - EORTC QLQ- Hepatocellular Carcinoma Domain (HCC 18)
Baseline up to Off-Treatment Visit (approximately up to 3.8 years)
- +2 more secondary outcomes
Other Outcomes (3)
Disease Control Rate (DCR)
From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (approximately up to 3.8 years)
Clinical Benefit Rate (CBR)
From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (approximately up to 3.8 years)
Percent Change From Baseline in Serum Biomarker
Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 7 Day 1, Cycle 8 Day 1, Cycle 9 Day 1 and at the Off-Treatment Visit (approximately up to 3.8 years)
Study Arms (2)
Lenvatinib
ACTIVE COMPARATORParticipants received lenvatinib capsules 12 milligram (mg) based on the participant's body weight greater than or equal to (\>=) 60 kilogram (kg) or 8 mg based on the participant's body weight less than (\<) 60 kg at baseline, orally, once daily (QD) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Sorafenib
ACTIVE COMPARATORParticipants received sorafenib 400 mg tablets, orally, twice daily (BID) in continuous 28-day treatment cycles up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Interventions
Eligibility Criteria
You may not qualify if:
- Imaging findings for HCC corresponding to any of the following:
- HCC with \>=50 percent liver occupation
- Clear invasion into the bile duct
- Portal vein invasion at the main portal branch (Vp4).
- Participants who have received any systemic chemotherapy, including anti-vascular endothelial growth factor (VEGF) therapy, or any systemic investigational anticancer agents, including lenvatinib, for advanced/unresectable HCC. Note: Participants who have received local hepatic injection chemotherapy are eligible.
- Participants 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, eg, granulocyte colony-stimulating factor \[G-CSF\]) within 28 days prior to randomization.
- Participants who have not recovered from toxicities as a result of prior anticancer therapy, except alopecia and infertility. Recovery is defined as \< Grade 2 severity per Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0).
- Significant cardiovascular impairment: history of congestive heart failure \> New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment at Screening.
- Prolongation of corrected QT interval (QTc) interval to \>480 millisecond (ms)
- Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib in the opinion of the investigator.
- Bleeding or thrombotic disorders or use of anticoagulants requiring therapeutic INR monitoring, eg, warfarin or similar agents. Treatment with low molecular weight heparin and factor X inhibitors which do not require INR monitoring is permitted. Antiplatelet agents are prohibited throughout the study.
- Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 28 days prior to randomization.
- Gastric or esophageal varices that require interventional treatment within 28 days prior to randomization. Prophylaxis with pharmacologic therapy (eg, nonselective beta-blocker) is permitted.
- Active malignancy (except for HCC or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 36 months.
- Participants whose only target lesion(s) is in bone will be excluded.
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Eisai Limitedlead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (186)
Facility # 1
Los Angeles, California, United States
Facility # 1
Sacramento, California, United States
Facility # 1
San Francisco, California, United States
Facility # 1
Washington D.C., District of Columbia, United States
Facility # 1
Tampa, Florida, United States
Facility # 1
Duluth, Georgia, United States
Facility # 1
Lawrenceville, Georgia, United States
Facility # 1
Baltimore, Maryland, United States
Facility # 1
Detroit, Michigan, United States
Facility # 1
Kansas City, Missouri, United States
Facility # 1
St Louis, Missouri, United States
Facility # 1
East Orange, New Jersey, United States
Facility # 1
Brooklyn, New York, United States
Facility # 1
Lake Success, New York, United States
Facility # 1
New York, New York, United States
Facility # 1
Charlotte, North Carolina, United States
Facility # 1
Durham, North Carolina, United States
Facility # 1
Portland, Oregon, United States
Facility # 1
Austin, Texas, United States
Facility # 1
Lubbock, Texas, United States
Facility # 1
Seattle, Washington, United States
Facility # 1
Camperdown, New South Wales, Australia
Facility # 1
Wentworthville, New South Wales, Australia
Facility # 1
Woolloongabba, Queensland, Australia
Facility # 1
Fitzroy, Victoria, Australia
Facility # 1
Melbourne, Victoria, Australia
Facility # 2
Melbourne, Victoria, Australia
Facility # 1
Nedlands, Western Australia, Australia
Facility # 1
Brussels, Belgium
Facility # 1
Edegem, Belgium
Facility # 1
Liège, Belgium
Facility # 1
Ottawa, Ontario, Canada
Facility # 1
Hefei, Anhui, China
Facility # 1
Beijing, Beijing Municipality, China
Facility # 2
Beijing, Beijing Municipality, China
Facility # 3
Beijing, Beijing Municipality, China
Facility # 1
Chongqing, Chongqing Municipality, China
Facility # 1
Fuzhou, Fujian, China
Facility # 2
Fuzhou, Fujian, China
Facility # 1
Guangzhou, Guangdong, China
Facility # 1
Harbin, Heilongjiang, China
Facility # 1
Changsha, Hunan, China
Facility # 1
Nanjing, Jiangsu, China
Facility # 1
Suzhou, Jiangsu, China
Facility # 1
Changchun, Jilin, China
Facility # 1
Dalian, Liaoning, China
Facility # 1
Jinan, Shandong, China
Facility # 1
Shanghai, Shanghai Municipality, China
Facility # 3
Shanghai, Shanghai Municipality, China
Facility # 1
Xi’an, Shanxi, China
Facility # 2
Xi’an, Shanxi, China
Facility # 1
Hangzhou, Zhejiang, China
Facility # 1
Tianjin, Zhejiang, China
Facility # 1
Nice, Alpes Maritimes, France
Facility # 1
Pessac, Gironde, France
Facility # 1
Toulouse, Haute Garonne, France
Facility # 1
Montpellier, Herault, France
Facility # 1
Rennes, Ille Et Vilaine, France
Facility # 1
Vandœuvre-lès-Nancy, Meurthe Et Moselle, France
Facility # 1
Amiens, Somme, France
Facility # 1
Créteil, Val De Marne, France
Facility # 1
Bordeaux, France
Facility # 1
Lille, France
Facility # 1
Lyon, France
Facility # 1
Nord, 59037, France
Facility # 1
Paris, 75013, France
Facility # 1
Paris, 75020, France
Facility # 1
Rhone, France
Facility # 1
Heidelberg, Baden-Wurttemberg, Germany
Facility # 1
Tübingen, Baden-Wurttemberg, Germany
Facility # 1
Marburg, Hesse, Germany
Facility # 1
Hanover, Lower Saxony, Germany
Facility # 1
Cologne, North Rhine-Westphalia, Germany
Facility # 1
Essen, North Rhine-Westphalia, Germany
Facility # 1
Mainz, Rhineland-Palatinate, Germany
Facility # 1
Hong Kong, Hong Kong
Facility # 2
Hong Kong, Hong Kong
Facility # 3
Hong Kong, Hong Kong
Facility # 1
Kowloon, Hong Kong
Facility # 1
Petah Tikva, Israel
Facility # 1
Torrette, Ancona, Italy
Facility # 1
Bari, Italy
Facility # 1
Benevento, Italy
Facility # 1
Bologna, Italy
Facility # 1
Napoli, Italy
Facility # 2
Napoli, Italy
Facility # 1
Palermo, Italy
Facility # 1
Roma, Italy
Facility # 1
Nagoya, Aichi-ken, Japan
Facility # 1
Kashiwa, Chiba, Japan
Facility # 1
Matsuyama, Ehime, Japan
Facility # 1
Kurume, Fukuoka, Japan
Facility # 1
Sapporo, Hokkaido, Japan
Facility # 2
Sapporo, Hokkaido, Japan
Facility # 1
Nishinomiya, Hyōgo, Japan
Facility # 1
Kanazawa, Ishikawa-ken, Japan
Facility # 1
Kawasaki, Kanagawa, Japan
Facility # 1
Yokohama, Kanagawa, Japan
Facility # 1
Tsu, Mie-ken, Japan
Facility # 1
Ōmura, Nagasaki, Japan
Facility # 1
Ōsaka-sayama, Osaka, Japan
Facility # 1
Bunkyo-Ku, Tokyo, Japan
Facility # 1
Chuo-ku, Tokyo, Japan
Facility # 1
Koto-ku, Tokyo, Japan
Facility # 1
Minato-ku, Tokyo, Japan
Facility # 1
Musashino, Tokyo, Japan
Facility # 1
Shimonoseki, Yamaguchi, Japan
Facility # 1
Fukuoka, Japan
Facility # 1
Hiroshima, Japan
Facility # 1
Okayama, Japan
Facility # 2
Osaka, Japan
Facility # 1
Saga, Japan
Facility # 2
Saga, Japan
Facility # 1
Kuantan, Pahang, Malaysia
Facility # 1
George Town, Pulau Pinang, Malaysia
Facility # 1
Miri, Sarawak, Malaysia
Facility # 1
Batu Caves, Selangor, Malaysia
Facility # 1
Kuala Lumpur, Malaysia
Facility # 1
Cebu City, Philippines
Facility # 2
Cebu City, Philippines
Facility # 1
Davao City, Philippines
Facility # 1
Quezon City, Philippines
Facility # 2
Quezon City, Philippines
Facility # 1
Gdansk, Poland
Facility # 1
Warsaw, Poland
Facility # 1
Wroclaw, Poland
Facility # 1
Arkhangelsk, Russia
Facility # 1
Moscow, Russia
Facility # 2
Moscow, Russia
Facility # 3
Saint Petersburg, Russia
Facility # 4
Saint Petersburg, Russia
Facility # 1
Ufa, Russia
Facility # 1
Singapore, Singapore
Facility # 2
Singapore, Singapore
Facility # 3
Singapore, Singapore
Facility # 4
Singapore, Singapore
Facility # 1
Goyang-si, Gyeonggi-do, South Korea
Facility # 1
Seongnam-si, Gyeonggi-do, South Korea
Facility # 2
Seongnam-si, Gyeonggi-do, South Korea
Facility # 1
Suwon, Gyeonggi-do, South Korea
Facility # 1
Daegu, Gyeongsangbuk-do, South Korea
Facility # 1
Hwasun, Jeollanam-do, South Korea
Facility # 1
Busan, South Korea
Facility # 2
Busan, South Korea
Facility # 3
Busan, South Korea
Facility # 1
Incheon, South Korea
Facility # 1
Seoul, South Korea
Facility # 2
Seoul, South Korea
Facility # 3
Seoul, South Korea
Facility # 4
Seoul, South Korea
Facility # 5
Seoul, South Korea
Facility # 6
Seoul, South Korea
Facility # 7
Seoul, South Korea
Facility # 8
Seoul, South Korea
Facility # 1
L'Hospitalet de Llobregat, Barcelona, Spain
Facility # 1
Santander, Cantabria, Spain
Facility # 1
Badajoz, Spain
Facility # 1
Girona, Spain
Facility # 1
Madrid, Spain
Facility # 2
Madrid, Spain
Facility # 3
Madrid, Spain
Facility # 4
Madrid, Spain
Facility # 1
Kaohsiung City, Taiwan
Facility # 2
Kaohsiung City, Taiwan
Facility # 1
Taichung, Taiwan
Facility # 2
Taichung, Taiwan
Facility # 1
Tainan, Taiwan
Facility # 2
Tainan, Taiwan
Facility # 1
Taipei, Taiwan
Facility # 2
Taipei, Taiwan
Facility # 3
Taipei, Taiwan
Facility # 4
Taipei, Taiwan
Facility # 5
Taipei, Taiwan
Facility # 1
Taoyuan, Taiwan
Facility # 1
Bangkoknoi, Bangkok, Thailand
Facility # 1
Pathum Wan, Bangkok, Thailand
Facility # 1
Ratchathewi, Bangkok, Thailand
Facility # 1
Muang, Changwat Chiang Rai, Thailand
Facility # 1
Muang, Chiang Mai, Thailand
Facility # 2
London, Greater London, W12 OHS, United Kingdom
Facility # 1
London, Greater London, United Kingdom
Facility # 3
London, Greater London, United Kingdom
Facility # 1
Manchester, Greater Manchester, United Kingdom
Facility # 1
Liverpool, Merseyside, United Kingdom
Facility # 1
Glasgow, Strathclyde, United Kingdom
Facility # 1
Birmingham, West Midlands, United Kingdom
Related Publications (9)
Piscaglia F, Ikeda K, Cheng AL, Kudo M, Ikeda M, Breder V, Ryoo BY, Mody K, Ren M, Ramji Z, Sung MW. Association between treatment-emergent hypertension and survival with lenvatinib treatment for patients with hepatocellular carcinoma in the REFLECT study. Cancer. 2024 Apr 15;130(8):1281-1291. doi: 10.1002/cncr.35185. Epub 2024 Jan 23.
PMID: 38261521DERIVEDKudo M, Finn RS, Qin S, Han KH, Ikeda K, Cheng AL, Vogel A, Tovoli F, Ueshima K, Aikata H, Lopez CL, Pracht M, Meng Z, Daniele B, Park JW, Palmer D, Tamai T, Saito K, Dutcus CE, Lencioni R. Overall survival and objective response in advanced unresectable hepatocellular carcinoma: A subanalysis of the REFLECT study. J Hepatol. 2023 Jan;78(1):133-141. doi: 10.1016/j.jhep.2022.09.006. Epub 2022 Sep 20.
PMID: 36341767DERIVEDHuynh J, Cho MT, Kim EJ, Ren M, Ramji Z, Vogel A. Lenvatinib in patients with unresectable hepatocellular carcinoma who progressed to Child-Pugh B liver function. Ther Adv Med Oncol. 2022 Aug 24;14:17588359221116608. doi: 10.1177/17588359221116608. eCollection 2022.
PMID: 36051472DERIVEDVogel A, Qin S, Kudo M, Su Y, Hudgens S, Yamashita T, Yoon JH, Fartoux L, Simon K, Lopez C, Sung M, Mody K, Ohtsuka T, Tamai T, Bennett L, Meier G, Breder V. Lenvatinib versus sorafenib for first-line treatment of unresectable hepatocellular carcinoma: patient-reported outcomes from a randomised, open-label, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2021 Aug;6(8):649-658. doi: 10.1016/S2468-1253(21)00110-2. Epub 2021 Jun 2.
PMID: 34087115DERIVEDOkusaka T, Ikeda K, Kudo M, Finn R, Qin S, Han KH, Cheng AL, Piscaglia F, Kobayashi M, Sung M, Chen M, Wyrwicz L, Yoon JH, Ren Z, Mody K, Dutcus C, Tamai T, Ren M, Hayato S, Kumada H. Safety and efficacy of lenvatinib by starting dose based on body weight in patients with unresectable hepatocellular carcinoma in REFLECT. J Gastroenterol. 2021 Jun;56(6):570-580. doi: 10.1007/s00535-021-01785-0. Epub 2021 May 4.
PMID: 33948712DERIVEDBriggs A, Daniele B, Dick K, Evans TRJ, Galle PR, Hubner RA, Lopez C, Siebert U, Tremblay G. Covariate-adjusted analysis of the Phase 3 REFLECT study of lenvatinib versus sorafenib in the treatment of unresectable hepatocellular carcinoma. Br J Cancer. 2020 Jun;122(12):1754-1759. doi: 10.1038/s41416-020-0817-7. Epub 2020 Apr 8.
PMID: 32265508DERIVEDYamashita T, Kudo M, Ikeda K, Izumi N, Tateishi R, Ikeda M, Aikata H, Kawaguchi Y, Wada Y, Numata K, Inaba Y, Kuromatsu R, Kobayashi M, Okusaka T, Tamai T, Kitamura C, Saito K, Haruna K, Okita K, Kumada H. REFLECT-a phase 3 trial comparing efficacy and safety of lenvatinib to sorafenib for the treatment of unresectable hepatocellular carcinoma: an analysis of Japanese subset. J Gastroenterol. 2020 Jan;55(1):113-122. doi: 10.1007/s00535-019-01642-1. Epub 2019 Nov 12.
PMID: 31720835DERIVEDEvans TRJ, Kudo M, Finn RS, Han KH, Cheng AL, Ikeda M, Kraljevic S, Ren M, Dutcus CE, Piscaglia F, Sung MW. Urine protein:creatinine ratio vs 24-hour urine protein for proteinuria management: analysis from the phase 3 REFLECT study of lenvatinib vs sorafenib in hepatocellular carcinoma. Br J Cancer. 2019 Jul;121(3):218-221. doi: 10.1038/s41416-019-0506-6. Epub 2019 Jun 28.
PMID: 31249394DERIVEDKudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1.
PMID: 29433850DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Eisai Medical Information
- Organization
- Eisai Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 2, 2013
First Posted
January 4, 2013
Study Start
March 1, 2013
Primary Completion
November 13, 2016
Study Completion
March 10, 2021
Last Updated
April 5, 2022
Results First Posted
September 25, 2018
Record last verified: 2022-03