Clinical trial NCT02811861: Lenvatinib/Everolimus or Lenvatinib/Pembrolizumab Versus Sunitinib Alone as Treatment of Advanced Renal Cell Carcinoma
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Renal Cell Carcinoma
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
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2016-06-23
Enrollment: 1069
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

1. Histological or cytological confirmation of RCC with a clear-cell component (original tissue diagnosis of RCC is acceptable).
2. Documented evidence of advanced RCC.
3. 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.

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 \<=1.5\*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.

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.

Exclusion Criteria:

1. 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.
2. 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
3. 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
4. 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
5. Participants who are using other investigational agents or who had received investigational drugs \<=4 weeks prior to study treatment start.
6. 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.
7. 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
8. 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
9. 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
10. Prolongation of corrected QT (QTc) interval to \>480 milliseconds (ms)
11. Participants who have not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy.
12. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib, everolimus, and/or sunitinib.
13. 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
14. Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
15. 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
16. Active infection (any infection requiring systemic treatment)
17. Participants known to be positive for Human Immunodeficiency Virus (HIV).
18. 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)
19. Known history of, or any evidence of, interstitial lung disease
20. Has a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis
21. 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
22. 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.
23. 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.
24. 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.
25. 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.
26. Known intolerance to any of the study drugs (or any of the excipients)
27. Participant has had an allogenic tissue/solid organ transplant.

Primary outcomes:
measure: Progression-free Survival (PFS) by Independent Imaging Review (IIR)
timeFrame: 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:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 69 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 69 months
measure: Number of Participants With At Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Up to approximately 69 months
measure: Number of Participants Who Discontinued Treatment Due to Toxicity
timeFrame: Up to approximately 69 months
measure: Time to Treatment Failure Due to Toxicity
timeFrame: Up to approximately 69 months
measure: Health-Related Quality of Life (HRQoL) Assessed by Functional Assessment of Cancer Therapy Kidney Syndrome Index-Disease-Related Symptoms (FKSI-DRS) Scores
timeFrame: Up to approximately 69 months
measure: HRQoL Assessed by European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Score
timeFrame: Up to approximately 69 months
measure: HRQoL Assessed by European Quality of Life (EuroQol) Five-Dimensional, 3-Level (EQ-5D-3L) Score
timeFrame: Up to approximately 69 months
measure: PFS on Next-line of Therapy (PFS2)
timeFrame: Up to approximately 69 months
measure: PFS by Investigator Assessment
timeFrame: Up to approximately 69 months
measure: Model-predicted Clearance for Lenvatinib and Everolimus
timeFrame: 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)
measure: Area Under the Plasma Drug Concentration-time Curve (AUC) for Lenvatinib and Everolimus
timeFrame: 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
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford School of Medicine
state: California
city: Boca Raton
country: United States
facility: Boca Raton Community Hospital
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists ( North Region)
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Joliet
country: United States
facility: Joliet Oncology - Hematology Associates
state: Illinois
city: Tinley Park
country: United States
facility: Healthcare Research Network III, LLC
state: Illinois
city: Overland Park
country: United States
facility: Health Midwest Ventures Group, Inc d/b/a HCA MidAmerica Division, LLC
state: Kansas
city: Topeka
country: United States
facility: Cotton-Oneil Clinical Research Center
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Bethesda
country: United States
facility: Associates in Oncology & Hematology, PC
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital- MGH
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Center
state: Michigan
city: Omaha
country: United States
facility: GU Research Network
state: Nebraska
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Rosewell Park Cancer Institute
state: New York
city: Johnson City
country: United States
facility: Broome Oncology
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Asheville
country: United States
facility: Mission Hospital_ Cancer Care of Western North Carolina
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: SCRI - Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology PA
state: Texas
city: McAllen
country: United States
facility: Texas Oncology PA - McAllen
state: Texas
city: Paris
country: United States
facility: Texas Oncology PA - Paris
state: Texas
city: The Woodlands
country: United States
facility: USOR Texas Oncology
state: Texas
city: Tyler
country: United States
facility: Texas Oncology PA - Tyler
state: Texas
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Hobart
country: Australia
facility: Royal Hobart Hospital
city: Macquarie park
country: Australia
facility: Macquarie University Hospital
city: South Brisbane
country: Australia
facility: ICON Cancer Foundation
city: St Albans
country: Australia
facility: Sunshine Hospital
city: Innsbruck
country: Austria
facility: Medizinische Universitat Innsbruck
city: Linz
country: Austria
facility: Krankenhaus der barmherzigen Schwestern Linz
city: Vienna
country: Austria
facility: AKH - Medizinische Universität Wien
city: Aalst
country: Belgium
facility: O.L.V Ziekenhuis
city: Antwerpen
country: Belgium
facility: ZNA Middelheim
city: Bonheiden
country: Belgium
facility: Imeldaziekenhuis
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis - Campus Virga Jesse
city: Liege
country: Belgium
facility: Domaine Universitaire
city: Wilrijk
country: Belgium
facility: GZA Ziekenhuizen - Campus Sint-Augustinus
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: BC Cancer Agency Vancouver Centre
state: British Columbia
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: London
country: Canada
facility: London Institute of Health Sciences
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute - University of Toronto
state: Ontario
city: Greenfield Park
country: Canada
facility: Centre de santé et de services sociaux Champlain-Charles-Le Moyne
state: Quebec
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne
city: Brno
country: Czechia
facility: Masarykuv onkologicky ustav
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc, Neurologicka klinika
city: Praha 4
country: Czechia
facility: Thomayerova nemocnice
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Praha 8
country: Czechia
facility: Nemocnice Na Bulovce
city: Angers
country: France
facility: ICO - Site Paul Papin
state: Maine Et Loire
city: Dijon cedex
country: France
facility: Centre Georges François Leclerc
city: Le Mans Cedex
country: France
facility: Clinique Victor Hugo - Centre Jean Bernard
city: Lyon
country: France
facility: Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes
city: Montpellier
country: France
facility: Institut Regional du Cancer de Montpellier
city: Paris
country: France
facility: Hopital la Petie Salpetriere
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Saint Herblain
country: France
facility: Boulevard du Professeur Jacques Monod
city: Strasbourg
country: France
facility: CHU Strasbourg - Nouvel Hopital Civil
city: Stuttgart
country: Germany
facility: EISAI Trial site 4
state: Baden Wuerttemberg
city: Tuebingen
country: Germany
facility: EISAI Trial site 1
state: Baden Wuerttemberg
city: München
country: Germany
facility: EISAI Trial site 7
state: Bayern
city: Frankfurt
country: Germany
facility: EISAI Trial site 6
state: Hessen
city: Greifswald
country: Germany
facility: EISAI Trial site 14
state: Mecklenburg-Vorpommern
city: Hannover
country: Germany
facility: EISAI Trial site 8
state: Niedersachsen
city: Münster
country: Germany
facility: EISAI Trial site 13
state: Nordrhein Westfalen
city: Homburg/Saar
country: Germany
facility: EISAI Trial site 2
state: Saarland
city: Berlin
country: Germany
facility: EISAI Trial site 5
city: Athens
country: Greece
facility: General Hospital of Athens "Alexandra"
city: Patras
country: Greece
facility: University of Patras Medical School
city: Thessaloníki
country: Greece
facility: General Hospital Papageorgiou
city: Thessaloníki
country: Greece
facility: Interbalkan Hospital of Thessaloniki
city: Cork
country: Ireland
facility: Cork University Hospital,Wilton
city: Dublin
country: Ireland
facility: Adelaide and Meath Hospital Incorp The National Children's Hospital
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Galway
country: Ireland
facility: University Hospital Galway
city: Be'er Ya'aqov
country: Israel
facility: Assaf Harofeh Medical Center
city: Haifa
country: Israel
facility: Rambam MC
city: Kfar-Saba
country: Israel
facility: Sapir Medical Center, Meir Hospital
city: Petah Tikva
country: Israel
facility: Rabin Medical Center-Beilinson Campus
city: Ramat-Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Faenza
country: Italy
facility: Azienda Unità Sanitaria Locale- Ravenna
state: Ravenna
city: Arezzo
country: Italy
facility: Ospedale San Donato
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico SantOrsola Malpighi
city: Genova
country: Italy
facility: Istituto Nazionale per la Ricerca sul Cancro di Genova
city: Lecce
country: Italy
facility: Presidio Ospedaliero Vito Fazzi
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Modena
country: Italy
facility: A.O.U. Policlinico di Modena
city: Napoli
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale A. Cardarelli
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Pavia
country: Italy
facility: I.R.C.S.S Fondazione Maugeri
city: Pordenone
country: Italy
facility: Azienda Ospedaliera Santa Maria Degli Angeli
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini
city: Rome
country: Italy
facility: Universita Campus Bio-Medico di Roma
city: Aichi
country: Japan
facility: Facility #1
city: Akita
country: Japan
facility: Facility #1
city: Aomori
country: Japan
facility: Facility #1
city: Chiba
country: Japan
facility: Facility #2
city: Fukuoka
country: Japan
facility: Facility #1
city: Hiroshima
country: Japan
facility: Facility #1
city: Hokkaido
country: Japan
facility: Facility #1
city: Hokkaido
country: Japan
facility: Facility #2
city: Hyogo
country: Japan
facility: Facility #1
city: Kagawa
country: Japan
facility: Facility #1
city: Kanagawa
country: Japan
facility: Facility #2
city: Kanagawa
country: Japan
facility: Facility #3
city: Nagasaki
country: Japan
facility: Facility #1
city: Nara
country: Japan
facility: Facility #1
city: Niigata
country: Japan
facility: Facility #1
city: Okayama
country: Japan
facility: Facility #1
city: Osaka
country: Japan
facility: Facility #1
city: Osaka
country: Japan
facility: Facility #2
city: Saitama
country: Japan
facility: Facility #1
city: Tokushima
country: Japan
facility: Facility #1
city: Tokyo
country: Japan
facility: Facility #1
city: Tokyo
country: Japan
facility: Facility #2
city: Tokyo
country: Japan
facility: Facility #3
city: Tokyo
country: Japan
facility: Facility #4
city: Tokyo
country: Japan
facility: Facility #5
city: Tokyo
country: Japan
facility: Facility #6
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center: Medical Oncology Department
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center: Urology Department
city: Seoul
country: Korea, Republic of
facility: Department of Internal Medicine Division of Hematology/Oncology Cancer center 11F
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
city: Szczecin
country: Poland
facility: SPWSZ w Szczecinie im. Marii Sklodowskiej-Curie
city: Moscow
country: Russian Federation
facility: FSBSI Russian Oncological Scientific Center n.a. N.N. Blokhin - Department of Oncology
city: Moscow
country: Russian Federation
facility: FSBI "Moscow scientific research oncology institute n.a. P.A. Gertsen" of MoH of RF
city: Moscow
country: Russian Federation
facility: FSBSI Russian Oncological Scientific Center n.a. N.N. Blokhin - Department of Urology
city: Nizhniy Novgorod
country: Russian Federation
facility: FBHI Privolzhskiy District Medical Centre FMBA of Russia
city: Novosibirsk
country: Russian Federation
facility: SBHI of Novosibirsk region "Novosibirsk Regional Oncological Dispensary"
city: Obninsk
country: Russian Federation
facility: FSBI "National Medical Research Radiological Center" of the MoH of the RF
city: Omsk
country: Russian Federation
facility: BHI of Omsk region "Clinical Oncology Dispensary"
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Barcelona
country: Spain
facility: ICO l'Hospitalet - Hospital Duran I Reynals
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Caceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario HM Madrid Sanchinarro
city: Madrid
country: Spain
facility: MD Anderson Cancer Centre
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Seville
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Oncologia
city: Bern
country: Switzerland
facility: Inselspital - Universitaetsspital Bern
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth General Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West Of Scotland Cancer Centre
city: Leeds
country: United Kingdom
facility: St. James's University Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Foundation Trust
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.