Lenvatinib/Everolimus or Lenvatinib/Pembrolizumab Versus Sunitinib Alone as Treatment of Advanced Renal Cell Carcinoma
CLEAR
A Multicenter, Open-label, Randomized, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib in Combination With Everolimus or Pembrolizumab Versus Sunitinib Alone in First-Line Treatment of Subjects With Advanced Renal Cell Carcinoma (CLEAR)
3 other identifiers
interventional
1,069
19 countries
180
Brief Summary
The primary purpose of the study is to demonstrate that lenvatinib in combination with everolimus (Arm A) or pembrolizumab (Arm B) is superior compared to sunitinib alone (Arm C) in improving progression-free survival (PFS) (by independent imaging review \[IIR\] using Response Evaluation Criteria in Solid Tumors \[RECIST 1.1\]) as first-line treatment in participants with advanced renal cell carcinoma (RCC).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Oct 2016
Longer than P75 for phase_3
180 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
June 21, 2016
CompletedFirst Posted
Study publicly available on registry
June 23, 2016
CompletedStudy Start
First participant enrolled
October 13, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 28, 2020
CompletedResults Posted
Study results publicly available
September 24, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
March 31, 2027
ExpectedFebruary 23, 2026
February 1, 2026
3.9 years
June 21, 2016
August 27, 2021
February 11, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free Survival (PFS) by Independent Imaging Review (IIR)
PFS assessed by IIR was defined as the time from the date of randomization to the date of the first documentation of progressive disease (PD) or death (whichever occurred first) using Response Evaluation Criteria in Solid Tumors (RECIST 1.1). PD was defined as at least a 20 percent (%) increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS was analyzed using Kaplan-Meier method.
From the date of randomization to the date of the first documentation of PD or date of death, whichever occurred first or up to data cutoff date 28 Aug 2020 (up to approximately 46 months)
Secondary Outcomes (12)
Objective Response Rate (ORR)
Up to approximately 69 months
Overall Survival (OS)
Up to approximately 69 months
Number of Participants With At Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Up to approximately 69 months
Number of Participants Who Discontinued Treatment Due to Toxicity
Up to approximately 69 months
Time to Treatment Failure Due to Toxicity
Up to approximately 69 months
- +7 more secondary outcomes
Study Arms (3)
Lenvatinib 18 mg plus Everolimus 5 mg
EXPERIMENTALLenvatinib 18 milligrams (mg) administered orally, once daily, plus everolimus 5 mg administered orally, once daily in each 21-day cycle.
Lenvatinib 20 mg plus Pembrolizumab 200 mg
EXPERIMENTALLenvatinib 20 mg administered orally, once daily, in each 21-day cycle plus pembrolizumab 200 mg administered intravenously (IV), every 3 weeks on Day 1 of each 21-day cycle.
Sunitinib 50 mg
ACTIVE COMPARATORSunitinib 50 mg administered orally, once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment in each 21-day cycle.
Interventions
Eligibility Criteria
You may qualify if:
- Histological or cytological confirmation of RCC with a clear-cell component (original tissue diagnosis of RCC is acceptable).
- Documented evidence of advanced RCC.
- At least 1 measurable target lesion according to RECIST 1.1 meeting the following criteria:
- Lymph node (LN) lesion that measures at least 1 dimension as greater than or equal to (\>=) 1.5 cm in the short axis
- Lymph node (LN) lesion that measures at least 1 dimension as greater than or equal to (\>=) 1.5 centimeter (cm) in the short axis
- Non-nodal lesion that measures greater than or equal to (\>=) 1.0 cm in the longest diameter
- The lesion is suitable for repeat measurement using computerized tomography/magnetic resonance imaging (CT/MRI). Lesions that have had external beam radiotherapy (EBRT) or locoregional therapy must show radiographic evidence of disease progression based on RECIST 1.1 to be deemed a target lesion.
- Karnofsky Performance Status (KPS) of \>=70 4.Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than or equal (\<=) 150/90 millimeter of mercury (mmHg) at Screening and no change in antihypertensive medications within 1 week prior to Cycle 1/Day 1 (C1/D1) 5.Adequate renal function defined as creatinine \<=1.5\*upper limit of normal (ULN); or for participants with creatinine greater than (\>) 1.5\*ULN, the calculated creatinine clearance \>=30 milliliters per minute (mL/min) (per the Cockcroft-Gault formula) is acceptable.
- Adequate bone marrow function defined by:
- Absolute neutrophil count (ANC) \>=1500/cubic millimeter (mm\^3)
- Platelets \>=100,000/mm\^3
- Hemoglobin \>=9 grams per deciliter (g/dL) NOTE: Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within the previous 2 weeks.
- Adequate blood coagulation function defined by International Normalized ratio (INR) \<=1.5 unless participant is receiving anticoagulant therapy, as long as INR is within therapeutic range of intended use of anticoagulants.
- Adequate liver function defined by:
- Total bilirubin \<=1.5\*ULN except for unconjugated hyperbilirubinemia of Gilbert's syndrome.
- +2 more criteria
You may not qualify if:
- Participants who have received any systemic anticancer therapy for RCC, including anti-vascular endothelial growth factor (VEGF) therapy, or any systemic investigational anticancer agent. Prior adjuvant treatment with an investigational anticancer agent is not allowed unless the investigator can provide evidence of participant's randomization to placebo arm.
- Participants with central nervous system (CNS) metastases are not eligible, unless they have completed local therapy (example, whole brain radiation therapy (WBRT), surgery or radiosurgery) and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (example, radiologic) or symptoms of CNS metastases must be stable for at least 4 weeks before starting study treatment
- Active malignancy (except for RCC, definitively treated basal or squamous cell carcinoma of the skin, and carcinoma in-situ of the cervix or bladder) within the past 24 months. Participants with history of localized \& low risk prostate cancer are allowed in the study if they were treated with curative intent and there is no prostate specific antigen (PSA) recurrence within the past 5 years
- Prior radiation therapy within 21 days prior to start of study treatment with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks prior to study treatment start
- Participants who are using other investigational agents or who had received investigational drugs \<=4 weeks prior to study treatment start.
- Received a live vaccine within 30 days of planned start of study treatment (Cycle 1/Day 1). Examples of live vaccines include, but are not limited to, measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (example, FluMist®) are live attenuated vaccines and are not allowed.
- Participants with proteinuria \>1+ on urine dipstick testing will undergo 24-h urine collection for quantitative assessment of proteinuria. Participants with urine protein \>=1 g/24 h will be ineligible
- Fasting total cholesterol \>300 milligram per deciliter (mg/dL) (or ˃7.75 millimole per liter (mmol/L)) and/or fasting triglycerides level ˃2.5 x upper limit of normal (ULN). Note: these participants can be included after initiation or adjustment of lipid-lowering medication
- Uncontrolled diabetes as defined by fasting glucose \>1.5 times the ULN. Note: these participants can be included after initiation or adjustment of glucose-lowering medication
- Prolongation of corrected QT (QTc) interval to \>480 milliseconds (ms)
- Participants who have not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy.
- Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib, everolimus, and/or sunitinib.
- Bleeding or thrombotic disorders or participants at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy
- Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
- Significant cardiovascular impairment within 12 months of the first dose of study drug: history of congestive heart failure greater than New York Heart Association Class II, unstable angina, myocardial infarction, cerebrovascular accident, or cardiac arrhythmia associated with hemodynamic instability. The following is also excluded: left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multiple-gated acquisition MUGA scan or echocardiogram
- +18 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Eisai Inc.lead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (183)
Stanford School of Medicine
Stanford, California, 94305-5826, United States
Boca Raton Community Hospital
Boca Raton, Florida, 33486, United States
Florida Cancer Specialists
Fort Myers, Florida, 33901, United States
University of Miami
Miami, Florida, 33136, United States
Mount Sinai Medical Center
Miami Beach, Florida, 33136, United States
Florida Hospital Cancer Institute
Orlando, Florida, 32804, United States
Florida Cancer Specialists ( North Region)
St. Petersburg, Florida, 33705, United States
Florida Cancer Specialists
West Palm Beach, Florida, 33401, United States
Joliet Oncology - Hematology Associates
Joliet, Illinois, 60435, United States
Healthcare Research Network III, LLC
Tinley Park, Illinois, 60487, United States
Health Midwest Ventures Group, Inc d/b/a HCA MidAmerica Division, LLC
Overland Park, Kansas, 66209, United States
Cotton-Oneil Clinical Research Center
Topeka, Kansas, 66604, United States
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121, United States
Associates in Oncology & Hematology, PC
Bethesda, Maryland, 20817, United States
Massachusetts General Hospital- MGH
Boston, Massachusetts, 02214, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Karmanos Cancer Center
Detroit, Michigan, 48201, United States
GU Research Network
Omaha, Nebraska, 68130, United States
Nebraska Cancer Specialists
Omaha, Nebraska, 68130, United States
Hackensack Medical Center
Hackensack, New Jersey, 07601, United States
Rosewell Park Cancer Institute
Buffalo, New York, 14263, United States
Broome Oncology
Johnson City, New York, 13790, United States
Weill Cornell Medical College New York Presbyterian Hospital
New York, New York, 10021, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Montefiore Medical Center
The Bronx, New York, 10461, United States
Mission Hospital_ Cancer Care of Western North Carolina
Asheville, North Carolina, 28801, United States
Oncology Hematology Care
Cincinnati, Ohio, 45242, United States
Medical University of South Carolina
Charleston, South Carolina, 29412, United States
SCRI - Tennessee Oncology
Nashville, Tennessee, 37203, United States
Texas Oncology, P.A.
Dallas, Texas, 75231, United States
Texas Oncology PA
Fort Worth, Texas, 76104, United States
Texas Oncology PA - McAllen
McAllen, Texas, 78503, United States
Texas Oncology PA - Paris
Paris, Texas, 75460, United States
USOR Texas Oncology
The Woodlands, Texas, 77380, United States
Texas Oncology PA - Tyler
Tyler, Texas, 75702, United States
Box Hill Hospital
Box Hill, Victoria, 3128, Australia
Austin Health
Heidelberg, Victoria, 3084, Australia
Royal Hobart Hospital
Hobart, Australia
Macquarie University Hospital
Macquarie Park, Australia
ICON Cancer Foundation
South Brisbane, Australia
Sunshine Hospital
St Albans, Australia
Medizinische Universitat Innsbruck
Innsbruck, Austria
Krankenhaus der barmherzigen Schwestern Linz
Linz, Austria
AKH - Medizinische Universität Wien
Vienna, 1090, Austria
O.L.V Ziekenhuis
Aalst, Belgium
ZNA Middelheim
Antwerp, 2260, Belgium
Imeldaziekenhuis
Bonheiden, Belgium
Institut Jules Bordet
Brussels, 1000, Belgium
Jessa Ziekenhuis - Campus Virga Jesse
Hasselt, 3500, Belgium
Domaine Universitaire
Liège, 4000, Belgium
GZA Ziekenhuizen - Campus Sint-Augustinus
Wilrijk, 2610, Belgium
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2, Canada
BC Cancer Agency Vancouver Centre
Vancouver, British Columbia, V5Z 1H7, Canada
St. Joseph's Healthcare Hamilton
Hamilton, Ontario, L8N 4A6, Canada
London Institute of Health Sciences
London, Ontario, N6A4L6, Canada
Ottawa Hospital Cancer Centre
Ottawa, Ontario, K1H 8, Canada
Sunnybrook Research Institute - University of Toronto
Toronto, Ontario, M4N 3M5, Canada
Centre de santé et de services sociaux Champlain-Charles-Le Moyne
Greenfield Park, Quebec, J4V 2H1, Canada
Fakultni nemocnice u sv. Anny v Brne
Brno, Czechia
Masarykuv onkologicky ustav
Brno, Czechia
Fakultni nemocnice Olomouc, Neurologicka klinika
Olomouc, Czechia
Fakultni nemocnice v Motole
Prague, Czechia
Nemocnice Na Bulovce
Prague, Czechia
Thomayerova nemocnice
Prague, Czechia
ICO - Site Paul Papin
Angers, Maine Et Loire, 49055, France
Centre Georges François Leclerc
Dijon, 21079, France
Clinique Victor Hugo - Centre Jean Bernard
Le Mans, France
Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes
Lyon, France
Institut Regional du Cancer de Montpellier
Montpellier, France
Hopital la Petie Salpetriere
Paris, cedex 13 75651, France
Hopital Europeen Georges Pompidou
Paris, France
Boulevard du Professeur Jacques Monod
Saint-Herblain, 4805, France
CHU Strasbourg - Nouvel Hopital Civil
Strasbourg, France
EISAI Trial site 4
Stuttgart, Baden-Wurttemberg, 70174, Germany
EISAI Trial site 1
Tübingen, Baden-Wurttemberg, 72076, Germany
EISAI Trial site 7
München, Bavaria, 81377, Germany
EISAI Trial site 6
Frankfurt am Main, Hesse, 60590, Germany
EISAI Trial site 8
Hanover, Lower Saxony, 30625, Germany
EISAI Trial site 14
Greifswald, Mecklenburg-Vorpommern, Germany
EISAI Trial site 13
Münster, North Rhine-Westphalia, 48149, Germany
EISAI Trial site 2
Homburg/Saar, Saarland, 66421, Germany
EISAI Trial site 5
Berlin, 12200, Germany
General Hospital of Athens "Alexandra"
Athens, 11528, Greece
University of Patras Medical School
Pátrai, 26504, Greece
General Hospital Papageorgiou
Thessaloniki, 56429, Greece
Interbalkan Hospital of Thessaloniki
Thessaloniki, 57001, Greece
Cork University Hospital,Wilton
Cork, Ireland
Adelaide and Meath Hospital Incorp The National Children's Hospital
Dublin, Ireland
Beaumont Hospital
Dublin, Ireland
University Hospital Galway
Galway, Ireland
Assaf Harofeh Medical Center
Be’er Ya‘aqov, Israel
Rambam MC
Haifa, Israel
Sapir Medical Center, Meir Hospital
Kfar Saba, Israel
Rabin Medical Center-Beilinson Campus
Petah Tikva, 49100, Israel
Chaim Sheba Medical Center
Ramat Gan, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, Israel
Azienda Unità Sanitaria Locale- Ravenna
Faenza, Ravenna, 48018, Italy
Ospedale San Donato
Arezzo, Italy
Azienda Ospedaliera Universitaria Policlinico SantOrsola Malpighi
Bologna, Italy
Istituto Nazionale per la Ricerca sul Cancro di Genova
Genova, 16132, Italy
Presidio Ospedaliero Vito Fazzi
Lecce, 73100, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST
Meldola, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133, Italy
A.O.U. Policlinico di Modena
Modena, 41124, Italy
Azienda Ospedaliera di Rilievo Nazionale A. Cardarelli
Naples, 80131, Italy
Istituto Nazionale Tumori Fondazione G. Pascale
Naples, Italy
Fondazione IRCCS Policlinico San Matteo
Pavia, Italy
I.R.C.S.S Fondazione Maugeri
Pavia, Italy
Azienda Ospedaliera Santa Maria Degli Angeli
Pordenone, 33170, Italy
Azienda Ospedaliera San Camillo Forlanini
Roma, Italy
Universita Campus Bio-Medico di Roma
Rome, Italy
Facility #1
Aichi, Japan
Facility #1
Akita, Japan
Facility #1
Aomori, Japan
Facility #2
Chiba, Japan
Facility #1
Fukuoka, Japan
Facility #1
Hiroshima, Japan
Facility #1
Hokkaido, Japan
Facility #2
Hokkaido, Japan
Facility #1
Hyōgo, Japan
Facility #1
Kagawa, Japan
Facility #2
Kanagawa, Japan
Facility #3
Kanagawa, Japan
Facility #1
Nagasaki, Japan
Facility #1
Nara, Japan
Facility #1
Niigata, Japan
Facility #1
Okayama, Japan
Facility #1
Osaka, Japan
Facility #2
Osaka, Japan
Facility #1
Saitama, Japan
Facility #1
Tokushima, Japan
Facility #1
Tokyo, Japan
Facility #2
Tokyo, Japan
Facility #3
Tokyo, Japan
Facility #4
Tokyo, Japan
Facility #5
Tokyo, Japan
Facility #6
Tokyo, Japan
Antoni van Leeuwenhoek
Amsterdam, 1066 CX, Netherlands
VU Medisch Centrum
Amsterdam, 1081 HV, Netherlands
UMC Utrecht
Utrecht, 3584 CX, Netherlands
Uniwersyteckie Centrum Kliniczne
Gdansk, Poland
Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
Lublin, Poland
SPWSZ w Szczecinie im. Marii Sklodowskiej-Curie
Szczecin, Poland
FSBSI Russian Oncological Scientific Center n.a. N.N. Blokhin - Department of Oncology
Moscow, 115478, Russia
FSBI "Moscow scientific research oncology institute n.a. P.A. Gertsen" of MoH of RF
Moscow, 125284, Russia
FSBSI Russian Oncological Scientific Center n.a. N.N. Blokhin - Department of Urology
Moscow, Russia
FBHI Privolzhskiy District Medical Centre FMBA of Russia
Nizhny Novgorod, Russia
SBHI of Novosibirsk region "Novosibirsk Regional Oncological Dispensary"
Novosibirsk, 630108, Russia
FSBI "National Medical Research Radiological Center" of the MoH of the RF
Obninsk, 249036, Russia
BHI of Omsk region "Clinical Oncology Dispensary"
Omsk, 644013, Russia
Kyungpook National University Chilgok Hospital
Daegu, 41404, South Korea
National Cancer Center
Goyang-si, South Korea
Asan Medical Center: Medical Oncology Department
Seoul, South Korea
Asan Medical Center: Urology Department
Seoul, South Korea
Department of Internal Medicine Division of Hematology/Oncology Cancer center 11F
Seoul, South Korea
Samsung Medical Center
Seoul, South Korea
Seoul National University Hospital
Seoul, South Korea
Severance Hospital, Yonsei University Health System
Seoul, South Korea
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, South Korea
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, 39008, Spain
Hospital Clinic i Provincial de Barcelona
Barcelona, 08036, Spain
ICO l'Hospitalet - Hospital Duran I Reynals
Barcelona, 08908, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain
Hospital Universitari Vall d'Hebron
Barcelona, Spain
Hospital San Pedro de Alcantara
Cáceres, 10003, Spain
Hospital Universitario Reina Sofia
Córdoba, Spain
Hospital Universitario Ramon y Cajal
Madrid, 28034, Spain
Hospital General Universitario Gregorio Maranon
Madrid, Spain
Hospital Universitario Clinico San Carlos
Madrid, Spain
Hospital Universitario HM Madrid Sanchinarro
Madrid, Spain
MD Anderson Cancer Centre
Madrid, Spain
Hospital Universitario Central de Asturias
Oviedo, 33011, Spain
Hospital Universitario Virgen del Rocio
Seville, Spain
Oncologia
Valencia, 46009, Spain
Inselspital - Universitaetsspital Bern
Bern, Switzerland
Royal Bournemouth General Hospital
Bournemouth, United Kingdom
Velindre Cancer Centre
Cardiff, United Kingdom
Western General Hospital
Edinburgh, United Kingdom
Beatson West Of Scotland Cancer Centre
Glasgow, G12 0YN, United Kingdom
St. James's University Hospital
Leeds, LS9 7TF, United Kingdom
Guy's Hospital
London, United Kingdom
Royal Free Hospital
London, United Kingdom
Christie Hospital NHS Foundation Trust
Manchester, M20 4BX, United Kingdom
Related Publications (12)
Fawsitt CG, Pan J, Orishaba P, Jackson CH, Thom H. Unanchored simulated treatment comparison on survival outcomes using parametric and Royston-Parmar models with application to lenvatinib plus pembrolizumab in renal cell carcinoma. BMC Med Res Methodol. 2025 Jan 30;25(1):26. doi: 10.1186/s12874-025-02480-x.
PMID: 39885377DERIVEDZheng H, Zhou J, Tong Y, Zhang J. Cost-Effectiveness Analysis of Lenvatinib plus Pembrolizumab or Everolimus as First-Line Treatment for Advanced Renal Cell Carcinoma. Clin Genitourin Cancer. 2025 Feb;23(1):102264. doi: 10.1016/j.clgc.2024.102264. Epub 2024 Nov 15.
PMID: 39642774DERIVEDMotzer RJ, Choueiri TK, Hutson T, Young Rha S, Puente J, Lalani AA, Winquist E, Eto M, Basappa NS, Tannir NM, Vaishampayan U, Bjarnason GA, Oudard S, Grunwald V, Burgents J, Xie R, McKenzie J, Powles T. Characterization of Responses to Lenvatinib plus Pembrolizumab in Patients with Advanced Renal Cell Carcinoma at the Final Prespecified Survival Analysis of the Phase 3 CLEAR Study. Eur Urol. 2024 Jul;86(1):4-9. doi: 10.1016/j.eururo.2024.03.015. Epub 2024 Apr 6.
PMID: 38582713DERIVEDMotzer RJ, Porta C, Eto M, Powles T, Grunwald V, Hutson TE, Alekseev B, Rha SY, Merchan J, Goh JC, Lalani AA, De Giorgi U, Melichar B, Hong SH, Gurney H, Mendez-Vidal MJ, Kopyltsov E, Tjulandin S, Gordoa TA, Kozlov V, Alyasova A, Winquist E, Maroto P, Kim M, Peer A, Procopio G, Takagi T, Wong S, Bedke J, Schmidinger M, Rodriguez-Lopez K, Burgents J, He C, Okpara CE, McKenzie J, Choueiri TK; CLEAR Trial Investigators. Lenvatinib Plus Pembrolizumab Versus Sunitinib in First-Line Treatment of Advanced Renal Cell Carcinoma: Final Prespecified Overall Survival Analysis of CLEAR, a Phase III Study. J Clin Oncol. 2024 Apr 10;42(11):1222-1228. doi: 10.1200/JCO.23.01569. Epub 2024 Jan 16.
PMID: 38227898DERIVEDGrunwald V, Powles T, Eto M, Kopyltsov E, Rha SY, Porta C, Motzer R, Hutson TE, Mendez-Vidal MJ, Hong SH, Winquist E, Goh JC, Maroto P, Buchler T, Takagi T, Burgents JE, Perini R, He C, Okpara CE, McKenzie J, Choueiri TK. Phase 3 CLEAR study in patients with advanced renal cell carcinoma: outcomes in subgroups for the lenvatinib-plus-pembrolizumab and sunitinib arms. Front Oncol. 2023 Aug 16;13:1223282. doi: 10.3389/fonc.2023.1223282. eCollection 2023.
PMID: 37664025DERIVEDRha SY, Choueiri TK, Matveev VB, Alyasova A, Hong SH, Gordoa TA, Gurney H, Bjarnason GA, Buchler T, Pedrazzoli P, Takagi T, Park SH, Lee JL, Perini RF, He CS, McKenzie JA, Eto M. Efficacy and safety of lenvatinib plus pembrolizumab vs sunitinib in the East Asian subset of patients with advanced renal cell carcinoma from the CLEAR trial. Int J Cancer. 2023 Sep 15;153(6):1241-1250. doi: 10.1002/ijc.34608. Epub 2023 Jun 9.
PMID: 37294085DERIVEDAldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.
PMID: 37146227DERIVEDMotzer R, George S, Merchan JR, Hutson TE, Song X, Perini RF, Xie R, Bapat U, Puente J. Characterization and Management of Adverse Reactions From the CLEAR Study in Advanced Renal Cell Carcinoma Treated With Lenvatinib Plus Pembrolizumab. Oncologist. 2023 Jun 2;28(6):501-509. doi: 10.1093/oncolo/oyac269.
PMID: 36866412DERIVEDChoueiri TK, Eto M, Motzer R, De Giorgi U, Buchler T, Basappa NS, Mendez-Vidal MJ, Tjulandin S, Hoon Park S, Melichar B, Hutson T, Alemany C, McGregor B, Powles T, Grunwald V, Alekseev B, Rha SY, Kopyltsov E, Kapoor A, Alonso Gordoa T, Goh JC, Staehler M, Merchan JR, Xie R, Perini RF, Mody K, McKenzie J, Porta CG. Lenvatinib plus pembrolizumab versus sunitinib as first-line treatment of patients with advanced renal cell carcinoma (CLEAR): extended follow-up from the phase 3, randomised, open-label study. Lancet Oncol. 2023 Mar;24(3):228-238. doi: 10.1016/S1470-2045(23)00049-9.
PMID: 36858721DERIVEDMotzer R, Porta C, Alekseev B, Rha SY, Choueiri TK, Mendez-Vidal MJ, Hong SH, Kapoor A, Goh JC, Eto M, Bennett L, Wang J, Pan JJ, Saretsky TL, Perini RF, He CS, Mody K, Cella D. Health-related quality-of-life outcomes in patients with advanced renal cell carcinoma treated with lenvatinib plus pembrolizumab or everolimus versus sunitinib (CLEAR): a randomised, phase 3 study. Lancet Oncol. 2022 Jun;23(6):768-780. doi: 10.1016/S1470-2045(22)00212-1. Epub 2022 Apr 27.
PMID: 35489363DERIVEDMotzer R, Alekseev B, Rha SY, Porta C, Eto M, Powles T, Grunwald V, Hutson TE, Kopyltsov E, Mendez-Vidal MJ, Kozlov V, Alyasova A, Hong SH, Kapoor A, Alonso Gordoa T, Merchan JR, Winquist E, Maroto P, Goh JC, Kim M, Gurney H, Patel V, Peer A, Procopio G, Takagi T, Melichar B, Rolland F, De Giorgi U, Wong S, Bedke J, Schmidinger M, Dutcus CE, Smith AD, Dutta L, Mody K, Perini RF, Xing D, Choueiri TK; CLEAR Trial Investigators. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med. 2021 Apr 8;384(14):1289-1300. doi: 10.1056/NEJMoa2035716. Epub 2021 Feb 13.
PMID: 33616314DERIVEDHofmann F, Hwang EC, Lam TB, Bex A, Yuan Y, Marconi LS, Ljungberg B. Targeted therapy for metastatic renal cell carcinoma. Cochrane Database Syst Rev. 2020 Oct 14;10(10):CD012796. doi: 10.1002/14651858.CD012796.pub2.
PMID: 33058158DERIVED
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
June 21, 2016
First Posted
June 23, 2016
Study Start
October 13, 2016
Primary Completion
August 28, 2020
Study Completion (Estimated)
March 31, 2027
Last Updated
February 23, 2026
Results First Posted
September 24, 2021
Record last verified: 2026-02