AzTrials
AzTrials

Renal Cell CarcinomaPhase 3CLEARNCT02811861

Lenvatinib/Everolimus or Lenvatinib/Pembrolizumab Versus Sunitinib Alone as Treatment of Advanced Renal Cell Carcinoma

A Phase 3 study testing Lenvatinib, Everolimus and Pembrolizumab in people with Renal Cell Carcinoma, run by Eisai Inc. at 183 sites in 20 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Renal Cell Carcinoma
What is being tested?
Lenvatinib, Everolimus and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,069 participants
Where
183 sitesin 20 countries
Study dates
13 Oct 2016to 31 Mar 2027
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.
  • 3.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 <=1.5upper limit of normal (ULN); or for participants with creatinine greater than (>) 1.5ULN, the calculated creatinine clearance >=30 milliliters per minute (mL/min) (per the Cockcroft-Gault formula) is acceptable.
  • 6.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.
  • 7.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.
  • 8.Adequate liver function defined by:
  • Total bilirubin <=1.5*ULN except for unconjugated hyperbilirubinemia of Gilbert's syndrome.
  • Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) <=3*ULN (in the case of liver metastases <=5*ULN), unless there are bone metastases. Participants with ALP values >3*ULN and known to have bone metastases can be included.
  • 9.Provide written informed consent. 10.Willing and able to comply with all aspects of the protocol.

Who cannot join

  • 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.
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  • 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
  • Active infection (any infection requiring systemic treatment)
  • Participants known to be positive for Human Immunodeficiency Virus (HIV).
  • Known active Hepatitis B (example, Hepatitis B surface antigen (HBsAg) reactive) or Hepatitis C (example, hepatitis C virus ribonucleic acid (HCV RNA) [qualitative] is detected)
  • Known history of, or any evidence of, interstitial lung disease
  • Has a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis
  • Participants with a diagnosis of immunodeficiency or who are receiving chronic systemic steroid therapy (doses exceeding 10 mg/day of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. Physiologic doses of corticosteroids (up to 10 mg/day of prednisone or equivalent) may be used during the study
  • Active autoimmune disease (with the exception of psoriasis) that has required systemic treatment in the past 2 years (that is, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (example, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
  • Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units of ß-hCG [or hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
  • Females of childbearing potential who:
  • Do not agree to use a highly effective method of contraception for the entire study period and for 120 days after study discontinuation, that is:
  • total abstinence (if it is their preferred and usual lifestyle)
  • an intrauterine device (IUD) or hormone-releasing system (IUS)
  • a contraceptive implant
  • an oral contraceptive (with additional barrier method) OR
  • Do not have a vasectomized partner with confirmed azoospermia. For sites outside of the EU, it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the participant, then the participant must agree to use a medically acceptable method of contraception, that is, double barrier methods of contraception such as condom plus diaphragm or cervical/vault cap with spermicide.
  • Males who have not had a successful vasectomy (confirmed azoospermia) and do not agree to use condom + spermicide OR have a female partner who does not meet the criteria above (that is, is of childbearing potential and not practicing highly effective contraception throughout the study period), starting with the first dose of study therapy through 120 days after the last dose of study therapy, unless sexually abstinent. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.
  • Known intolerance to any of the study drugs (or any of the excipients)
  • Participant has had an allogenic tissue/solid organ transplant.

Trial locations and contacts

183 sites in 20 countries.

183 sites in 20 countries

United States35 sites

  • Mission Hospital_ Cancer Care of Western North Carolina

    Asheville, North Carolina, 28801

  • Associates in Oncology & Hematology, PC

    Bethesda, Maryland, 20817

  • Boca Raton Community Hospital

    Boca Raton, Florida, 33486

  • Massachusetts General Hospital- MGH

    Boston, Massachusetts, 02214

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Rosewell Park Cancer Institute

    Buffalo, New York, 14263

  • Medical University of South Carolina

    Charleston, South Carolina, 29412

  • Oncology Hematology Care

    Cincinnati, Ohio, 45242

  • Texas Oncology, P.A.

    Dallas, Texas, 75231

  • Karmanos Cancer Center

    Detroit, Michigan, 48201

  • Florida Cancer Specialists

    Fort Myers, Florida, 33901

  • Texas Oncology PA

    Fort Worth, Texas, 76104

  • Hackensack Medical Center

    Hackensack, New Jersey, 07601

  • Broome Oncology

    Johnson City, New York, 13790

  • Joliet Oncology - Hematology Associates

    Joliet, Illinois, 60435

  • Texas Oncology PA - McAllen

    McAllen, Texas, 78503

  • University of Miami

    Miami, Florida, 33136

  • Mount Sinai Medical Center

    Miami Beach, Florida, 33136

  • SCRI - Tennessee Oncology

    Nashville, Tennessee, 37203

  • Ochsner Clinic Foundation

    New Orleans, Louisiana, 70121

  • Weill Cornell Medical College New York Presbyterian Hospital

    New York, New York, 10021

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • GU Research Network

    Omaha, Nebraska, 68130

  • Nebraska Cancer Specialists

    Omaha, Nebraska, 68130

  • Florida Hospital Cancer Institute

    Orlando, Florida, 32804

  • Health Midwest Ventures Group, Inc d/b/a HCA MidAmerica Division, LLC

    Overland Park, Kansas, 66209

  • Texas Oncology PA - Paris

    Paris, Texas, 75460

  • Florida Cancer Specialists ( North Region)

    St. Petersburg, Florida, 33705

  • Stanford School of Medicine

    Stanford, California, 94305-5826

  • Montefiore Medical Center

    The Bronx, New York, 10461

  • USOR Texas Oncology

    The Woodlands, Texas, 77380

  • Healthcare Research Network III, LLC

    Tinley Park, Illinois, 60487

  • Cotton-Oneil Clinical Research Center

    Topeka, Kansas, 66604

  • Texas Oncology PA - Tyler

    Tyler, Texas, 75702

  • Florida Cancer Specialists

    West Palm Beach, Florida, 33401

Other trials in United States

Japan26 sites

  • Facility #1

    Aichi

  • Facility #1

    Akita

  • Facility #1

    Aomori

  • Facility #2

    Chiba

  • Facility #1

    Fukuoka

  • Facility #1

    Hiroshima

  • Facility #1

    Hokkaido

  • Facility #2

    Hokkaido

  • Facility #1

    Hyōgo

  • Facility #1

    Kagawa

  • Facility #2

    Kanagawa

  • Facility #3

    Kanagawa

  • Facility #1

    Nagasaki

  • Facility #1

    Nara

  • Facility #1

    Niigata

  • Facility #1

    Okayama

  • Facility #1

    Osaka

  • Facility #2

    Osaka

  • Facility #1

    Saitama

  • Facility #1

    Tokushima

  • Facility #1

    Tokyo

  • Facility #2

    Tokyo

  • Facility #3

    Tokyo

  • Facility #4

    Tokyo

  • Facility #5

    Tokyo

  • Facility #6

    Tokyo

Other trials in Japan

Italy15 sites

  • Ospedale San Donato

    Arezzo

  • Azienda Ospedaliera Universitaria Policlinico SantOrsola Malpighi

    Bologna

  • Azienda Unità Sanitaria Locale- Ravenna

    Faenza, Ravenna, 48018

  • Istituto Nazionale per la Ricerca sul Cancro di Genova

    Genova, 16132

  • Presidio Ospedaliero Vito Fazzi

    Lecce, 73100

  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST

    Meldola

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan, 20133

  • A.O.U. Policlinico di Modena

    Modena, 41124

  • Azienda Ospedaliera di Rilievo Nazionale A. Cardarelli

    Naples, 80131

  • Istituto Nazionale Tumori Fondazione G. Pascale

    Naples

  • Fondazione IRCCS Policlinico San Matteo

    Pavia

  • I.R.C.S.S Fondazione Maugeri

    Pavia

  • Azienda Ospedaliera Santa Maria Degli Angeli

    Pordenone, 33170

  • Azienda Ospedaliera San Camillo Forlanini

    Roma

  • Universita Campus Bio-Medico di Roma

    Rome

Other trials in Italy

Spain15 sites

  • Hospital Clinic i Provincial de Barcelona

    Barcelona, 08036

  • ICO l'Hospitalet - Hospital Duran I Reynals

    Barcelona, 08908

  • Hospital de la Santa Creu i Sant Pau

    Barcelona

  • Hospital Universitari Vall d'Hebron

    Barcelona

  • Hospital San Pedro de Alcantara

    Cáceres, 10003

  • Hospital Universitario Reina Sofia

    Córdoba

  • Hospital Universitario Ramon y Cajal

    Madrid, 28034

  • Hospital General Universitario Gregorio Maranon

    Madrid

  • Hospital Universitario Clinico San Carlos

    Madrid

  • Hospital Universitario HM Madrid Sanchinarro

    Madrid

  • MD Anderson Cancer Centre

    Madrid

  • Hospital Universitario Central de Asturias

    Oviedo, 33011

  • Hospital Universitario Marques de Valdecilla

    Santander, Cantabria, 39008

  • Hospital Universitario Virgen del Rocio

    Seville

  • Oncologia

    Valencia, 46009

Other trials in Spain

France9 sites

  • ICO - Site Paul Papin

    Angers, Maine Et Loire, 49055

  • Centre Georges François Leclerc

    Dijon, 21079

  • Clinique Victor Hugo - Centre Jean Bernard

    Le Mans

  • Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes

    Lyon

  • Institut Regional du Cancer de Montpellier

    Montpellier

  • Hopital la Petie Salpetriere

    Paris, cedex 13 75651

  • Hopital Europeen Georges Pompidou

    Paris

  • Boulevard du Professeur Jacques Monod

    Saint-Herblain, 4805

  • CHU Strasbourg - Nouvel Hopital Civil

    Strasbourg

Other trials in France

Germany9 sites

  • EISAI Trial site 5

    Berlin, 12200

  • EISAI Trial site 6

    Frankfurt am Main, Hesse, 60590

  • EISAI Trial site 14

    Greifswald, Mecklenburg-Vorpommern

  • EISAI Trial site 8

    Hanover, Lower Saxony, 30625

  • EISAI Trial site 2

    Homburg/Saar, Saarland, 66421

  • EISAI Trial site 7

    München, Bavaria, 81377

  • EISAI Trial site 13

    Münster, North Rhine-Westphalia, 48149

  • EISAI Trial site 4

    Stuttgart, Baden-Wurttemberg, 70174

  • EISAI Trial site 1

    Tübingen, Baden-Wurttemberg, 72076

Other trials in Germany

South Korea9 sites

  • Kyungpook National University Chilgok Hospital

    Daegu, 41404

  • National Cancer Center

    Goyang-si

  • Asan Medical Center: Medical Oncology Department

    Seoul

  • Asan Medical Center: Urology Department

    Seoul

  • Department of Internal Medicine Division of Hematology/Oncology Cancer center 11F

    Seoul

  • Samsung Medical Center

    Seoul

  • Seoul National University Hospital

    Seoul

  • Severance Hospital, Yonsei University Health System

    Seoul

  • The Catholic University of Korea, Seoul St. Mary's Hospital

    Seoul

Other trials in South Korea

United Kingdom8 sites

  • Royal Bournemouth General Hospital

    Bournemouth

  • Velindre Cancer Centre

    Cardiff

  • Western General Hospital

    Edinburgh

  • Beatson West Of Scotland Cancer Centre

    Glasgow, G12 0YN

  • St. James's University Hospital

    Leeds, LS9 7TF

  • Guy's Hospital

    London

  • Royal Free Hospital

    London

  • Christie Hospital NHS Foundation Trust

    Manchester, M20 4BX

Other trials in United Kingdom

Belgium7 sites

  • O.L.V Ziekenhuis

    Aalst

  • ZNA Middelheim

    Antwerp, 2260

  • Imeldaziekenhuis

    Bonheiden

  • Institut Jules Bordet

    Brussels, 1000

  • Jessa Ziekenhuis - Campus Virga Jesse

    Hasselt, 3500

  • Domaine Universitaire

    Liège, 4000

  • GZA Ziekenhuizen - Campus Sint-Augustinus

    Wilrijk, 2610

Other trials in Belgium

Canada7 sites

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • Centre de santé et de services sociaux Champlain-Charles-Le Moyne

    Greenfield Park, Quebec, J4V 2H1

  • St. Joseph's Healthcare Hamilton

    Hamilton, Ontario, L8N 4A6

  • London Institute of Health Sciences

    London, Ontario, N6A4L6

  • Ottawa Hospital Cancer Centre

    Ottawa, Ontario, K1H 8

  • Sunnybrook Research Institute - University of Toronto

    Toronto, Ontario, M4N 3M5

  • BC Cancer Agency Vancouver Centre

    Vancouver, British Columbia, V5Z 1H7

Other trials in Canada

Russia7 sites

  • FSBSI Russian Oncological Scientific Center n.a. N.N. Blokhin - Department of Oncology

    Moscow, 115478

  • FSBI "Moscow scientific research oncology institute n.a. P.A. Gertsen" of MoH of RF

    Moscow, 125284

  • FSBSI Russian Oncological Scientific Center n.a. N.N. Blokhin - Department of Urology

    Moscow

  • FBHI Privolzhskiy District Medical Centre FMBA of Russia

    Nizhny Novgorod

  • SBHI of Novosibirsk region "Novosibirsk Regional Oncological Dispensary"

    Novosibirsk, 630108

  • FSBI "National Medical Research Radiological Center" of the MoH of the RF

    Obninsk, 249036

  • BHI of Omsk region "Clinical Oncology Dispensary"

    Omsk, 644013

Other trials in Russia

Australia6 sites

  • Box Hill Hospital

    Box Hill, Victoria, 3128

  • Austin Health

    Heidelberg, Victoria, 3084

  • Royal Hobart Hospital

    Hobart

  • Macquarie University Hospital

    Macquarie Park

  • ICON Cancer Foundation

    South Brisbane

  • Sunshine Hospital

    St Albans

Other trials in Australia

Czechia6 sites

  • Fakultni nemocnice u sv. Anny v Brne

    Brno

  • Masarykuv onkologicky ustav

    Brno

  • Fakultni nemocnice Olomouc, Neurologicka klinika

    Olomouc

  • Fakultni nemocnice v Motole

    Prague

  • Nemocnice Na Bulovce

    Prague

  • Thomayerova nemocnice

    Prague

Other trials in Czechia

Israel6 sites

  • Assaf Harofeh Medical Center

    Be’er Ya‘aqov

  • Rambam MC

    Haifa

  • Sapir Medical Center, Meir Hospital

    Kfar Saba

  • Rabin Medical Center-Beilinson Campus

    Petah Tikva, 49100

  • Chaim Sheba Medical Center

    Ramat Gan

  • Tel Aviv Sourasky Medical Center

    Tel Aviv

Other trials in Israel

Greece4 sites

  • General Hospital of Athens "Alexandra"

    Athens, 11528

  • University of Patras Medical School

    Pátrai, 26504

  • General Hospital Papageorgiou

    Thessaloniki, 56429

  • Interbalkan Hospital of Thessaloniki

    Thessaloniki, 57001

Other trials in Greece

Ireland4 sites

  • Cork University Hospital,Wilton

    Cork

  • Adelaide and Meath Hospital Incorp The National Children's Hospital

    Dublin

  • Beaumont Hospital

    Dublin

  • University Hospital Galway

    Galway

Other trials in Ireland

Austria3 sites

  • Medizinische Universitat Innsbruck

    Innsbruck

  • Krankenhaus der barmherzigen Schwestern Linz

    Linz

  • AKH - Medizinische Universität Wien

    Vienna, 1090

Other trials in Austria

Netherlands3 sites

  • Antoni van Leeuwenhoek

    Amsterdam, 1066 CX

  • VU Medisch Centrum

    Amsterdam, 1081 HV

  • UMC Utrecht

    Utrecht, 3584 CX

Other trials in Netherlands

Poland3 sites

  • Uniwersyteckie Centrum Kliniczne

    Gdansk

  • Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie

    Lublin

  • SPWSZ w Szczecinie im. Marii Sklodowskiej-Curie

    Szczecin

Other trials in Poland

Switzerland1 site

  • Inselspital - Universitaetsspital Bern

    Bern

Other trials in Switzerland

About this study

Official title: 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)

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).

Keywords
Renal Cell Carcinoma (RCC), Lenvatinib, First-line RCC, Treatment-naive RCC, Everolimus, Pembrolizumab, Sunitinib, Phase 3 RCC, Phase 3 first-line RCC, Phase 3 treatment-naive RCC
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02811861
Study groupRoleWhat they receive
Lenvatinib 18 mg plus Everolimus 5 mgExperimentalLenvatinib 18 milligrams (mg) administered orally, once daily, plus everolimus 5 mg administered orally, once daily in each 21-day cycle.
Receives: Drug: Lenvatinib; Drug: Everolimus
Lenvatinib 20 mg plus Pembrolizumab 200 mgExperimentalLenvatinib 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.
Receives: Drug: Lenvatinib; Drug: Pembrolizumab
Sunitinib 50 mgActive 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.
Receives: Drug: Sunitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. Objective Response Rate (ORR)

    ORR is defined as the proportion of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) as determined by IIR using RECIST 1.1. CR is defined as disappearance of all (targeted and non-target [NT]) lesions. All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (<) 10mm. PR: defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. To be considered a BOR, all responses had to be confirmed no less than 4 weeks after the initial assessment of response. Data for this outcome measure will be reported after study completion (anticipated study completion date is March 2026).

    Measured: Up to approximately 69 months

  2. Overall Survival (OS)

    OS is defined as the time from the date of randomization to the date of death from any cause. Participants who were lost to follow-up and those who were alive at the data cutoff date were censored, either at the last date the participant was last known alive or at the data cutoff date, whichever occurred first. Data for this outcome measure will be reported after study completion (anticipated study completion date is March 2026).

    Measured: Up to approximately 69 months

  3. Number of Participants With At Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    TEAEs were defined as those adverse events (AEs) that occurred (or worsened, if present at Baseline) after the first dose of study drug through 30 days after the last dose of study drug.An AE was defined as any untoward medical occurrence in a participants or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. A SAE was defined as any AE if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect. Data for this outcome measure will be reported after study completion (anticipated study completion date is March 2026).

    Measured: Up to approximately 69 months

  4. Number of Participants Who Discontinued Treatment Due to Toxicity

    Data for this outcome measure will be reported after study completion (anticipated study completion date is March 2026.

    Measured: Up to approximately 69 months

  5. Time to Treatment Failure Due to Toxicity

    Time to treatment failure due to toxicity is defined as time from the date of randomization to the date that a participant discontinued study treatment due to TEAEs. Data for this outcome measure will be reported after study completion (anticipated study completion date is March 2026).

    Measured: Up to approximately 69 months

  6. Health-Related Quality of Life (HRQoL) Assessed by Functional Assessment of Cancer Therapy Kidney Syndrome Index-Disease-Related Symptoms (FKSI-DRS) Scores

    The FKSI-DRS consisted of 9 items that experts and participants had indicated are important targets for the treatment of advanced kidney cancer, and that clinical experts had indicated are primarily disease-related, as opposed to treatment-related. Symptoms assessed on the FKSI-DRS included lack of energy, fatigue, weight loss, pain, bone pain, shortness of breath, cough, fever, or hematuria. Each item was scored on a 5-point Likert-type scale (0 = not at all; 4 = very much) where total score ranged from 0 (worst) to 36 (best), where higher scores correspond to better outcomes. Data for this outcome measure will be reported after study completion (anticipated study completion date is March 2026).

    Measured: Up to approximately 69 months

  7. HRQoL Assessed by European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Score

    EORTC QLQ-C30 is a questionnaire including 30 questions that rate the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores are transformed to a range of 0 to 100 using a standard EORTC algorithm. For the overall HRQoL and functioning scales, a higher score is correlated with better HRQoL, whereas a higher score represents worse HRQoL for symptom scales. Data for this outcome measure will be reported after study completion (anticipated study completion date is March 2026)

    Measured: Up to approximately 69 months

  8. HRQoL Assessed by European Quality of Life (EuroQol) Five-Dimensional, 3-Level (EQ-5D-3L) Score

    EQ-5D-3L is a health profile questionnaire consisting of the EQ-5D descriptive system and the EuroQol visual analog scale (EQ-VAS). For the EQ-5D, participants rate 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) at 1 of 3 levels (1=no problems; 2=some problems; 3=extreme problems). The EQ-5D Health Utilities Index (HUI) is derived from the five dimensions of the EQ-5D, using country-specific preference weights (tariffs) to summarize how good or bad each health state is on a scale from 1 (full health) to <0 (worse health/dead). The EQ-VAS measures self-rated global health status using a vertically oriented VAS, where 100 represents the "best imaginable health state" and 0 represents the "worst imaginable health state." Data for this outcome measure will be reported after study completion (anticipated study completion date is March 2026)

    Measured: Up to approximately 69 months

  9. PFS on Next-line of Therapy (PFS2)

    PFS2 is defined as the time from randomization to disease progression as assessed by investigator on next-line treatment or death from any cause (whichever occurred first). Data for this outcome measure will be reported after study completion (anticipated study completion date is March 2026)

    Measured: Up to approximately 69 months

  10. PFS by Investigator Assessment

    PFS by investigator assessment is defined as the time from the date of randomization to the date of first documentation of disease progression based on the investigator assessment per RECIST 1.1 or death (whichever occurred first). Data for this outcome measure will be reported after study completion (anticipated study completion date is March 2026).

    Measured: Up to approximately 69 months

  11. Model-predicted Clearance for Lenvatinib and Everolimus

    Data for this outcome measure will be reported after study completion (anticipated study completion date is March 2026)

    Measured: Cycles 1 and 2 Day 1; 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 15: predose and 2-12 hours postdose; Cycles 3, 4, 5 and 6 Day 1: predose (Cycle length=21 days)

  12. Area Under the Plasma Drug Concentration-time Curve (AUC) for Lenvatinib and Everolimus

    Data for this outcome measure will be reported after study completion (anticipated study completion date is March 2026)

    Measured: Cycles 1 and 2 Day 1; 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 15: predose and 2-12 hours postdose; Cycles 3, 4, 5 and 6 Day 1: predose (Cycle length = 21 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jun 2016 (estimated)
  2. Study start13 Oct 2016
  3. Primary completion28 Aug 2020
  4. Study completion31 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,069 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02811861
Sponsor's protocol ID
E7080-G000-307
Other IDs
KEYNOTE-581, 2016-000916-14, 2016
Acronym
CLEAR
Status last verified
Feb 2026
First submitted
21 Jun 2016
Last updated
23 Feb 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 39885377

  • Grunwald V, McKay RR, Buchler T, Eto M, Park SH, Takagi T, Zanetta S, Keizman D, Suarez C, Negrier S, Lee JL, Santini D, Bedke J, Staehler M, Kollmannsberger C, Choueiri TK, Motzer RJ, Burgents JE, Xie R, Okpara CE, Powles T. Clinical outcomes by baseline metastases in patients with renal cell carcinoma treated with lenvatinib plus pembrolizumab versus sunitinib: Post hoc analysis of the CLEAR trial. Int J Cancer. 2025 Apr 1;156(7):1326-1335. doi: 10.1002/ijc.35288. Epub 2024 Dec 30.

    PubMed 39739622

  • Zheng 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.

    PubMed 39642774

  • Motzer 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.

    PubMed 38582713

  • Motzer 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.

    PubMed 38227898

  • Grunwald 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.

    PubMed 37664025

  • Rha 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.

    PubMed 37294085

  • Aldin 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.

    PubMed 37146227

  • Motzer 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.

    PubMed 36866412

  • Choueiri 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.

    PubMed 36858721

  • Motzer 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.

    PubMed 35489363

  • Motzer 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.

    PubMed 33616314

  • Hofmann 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.

    PubMed 33058158

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Lenvatinib, Everolimus and Pembrolizumab in people with Renal Cell Carcinoma, run by Eisai Inc. at 183 sites in 20 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 23 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 183 sites in United States, Japan, Italy, Spain, France and 15 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) by Independent Imaging Review (IIR) (time frame: 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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02811861, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2026.

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