Trial to Assess Safety and Efficacy of Lenvatinib (18 mg vs. 14 mg) in Combination With Everolimus in Participants With Renal Cell Carcinoma
A Randomized, Open-Label (Formerly Double-Blind), Phase 2 Trial to Assess Safety and Efficacy of Lenvatinib at Two Different Starting Doses (18 mg vs. 14 mg QD) in Combination With Everolimus (5 mg QD) in Renal Cell Carcinoma Following One Prior VEGF-Targeted Treatment
2 other identifiers
interventional
343
16 countries
93
Brief Summary
Study E7080-G000-218 is a Randomized, open-label (formerly Double-blind), Phase 2 Trial conducted to assess whether a starting dose of lenvatinib 14 milligrams (mg) in combination with everolimus 5 mg once daily (QD) will provide comparable efficacy (based on objective response rate \[ORR\] at 24 weeks \[ORR24W\]) with an improved safety profile compared to lenvatinib 18 mg in combination with everolimus 5 mg (based on treatment-emergent intolerable Grade 2, or any greater than or equal to (\>=) Grade 3 adverse events (AEs) in the first 24 weeks after randomization).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Aug 2017
Longer than P75 for phase_2
93 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
May 22, 2017
CompletedFirst Posted
Study publicly available on registry
June 2, 2017
CompletedStudy Start
First participant enrolled
August 17, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 14, 2020
CompletedResults Posted
Study results publicly available
March 5, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
June 20, 2024
CompletedApril 1, 2025
March 1, 2025
2.5 years
May 22, 2017
February 12, 2021
March 12, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Objective Response Rate at Week 24 (ORR24W)
ORR24W was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) at the Week 24 (after randomization) time point, during treatment or within 28 days after the last dose date but on or prior to the start of new anticancer therapy based on investigator assessment according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR: defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (\<) 10 millimeters (mm). PR: defined as at least a 30 percent (%) 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.
At Week 24
Percentage of Participants With Intolerable Grade 2 or Any Grade >=Grade 3 TEAEs Within 24 Weeks
TEAE was defined as an adverse event (AE) with an onset that had occurred after receiving study drug. A severity grade was defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. As per NCI-CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE.
Up to Week 24
Secondary Outcomes (16)
Progression-free Survival (PFS)
From the date of randomization to the date of the first documentation of PD or date of death, whichever occurred first or up to date of data cutoff for the primary analysis (up to 29 months)
Objective Response Rate (ORR)
From date of randomization up to first documentation of PD or date of death, whichever occurred first or up to the date of data cut off for the primary analysis (up to 29 months)
Number of Participants With TEAEs and Serious TEAEs
From date of first dose of study drug up to 28 days after last dose of study drug (up to 71 months)
Percentage of Participants Who Discontinued Treatment Due to Toxicity
From date of first dose of study drug up to 28 days after last dose of study drug (up to 71 months)
Time to Treatment Failure Due to Toxicity
From the date of randomization to the date of discontinuation of study treatment due to TEAEs, or date of data cut off for the primary analysis (up to 29 months)
- +11 more secondary outcomes
Study Arms (2)
Lenvatinib 14 mg plus everolimus 5 mg
EXPERIMENTALParticipants will receive oral lenvatinib 14 mg once daily (QD) plus oral everolimus 5 mg QD as the starting dose for Cycle 1. If there are no intolerable Grade 2 or any \>= Grade 3 treatment-emergent adverse events (TEAEs) that require dose reduction in the first 28-day cycle (that is, the first 4 weeks of treatment), the lenvatinib dose will be escalated to 18 mg QD (plus everolimus 5 mg) beginning in Cycle 2 or later (cycle length equal to \[=\] 28 days) during randomization phase. After the data cutoff for the primary analysis, participants will receive study treatment as continuous 56-day cycles.
Lenvatinib 18 mg plus everolimus 5 mg
EXPERIMENTALParticipants will receive oral lenvatinib 18 mg QD plus oral everolimus 5 mg QD as the starting dose in Cycle 1 or later (cycle length =28 days) during randomization phase. After the data cutoff for the primary analysis, participants will receive study treatment as continuous 56-day cycles.
Interventions
lenvatinib capsules.
everolimus tablets.
Eligibility Criteria
You may qualify if:
- Histological or cytological confirmation of predominant clear cell renal cell carcinoma (RCC) (original tissue diagnosis of RCC is acceptable)
- Documented evidence of advanced RCC
- One prior disease progression episode on or after vascular endothelial growth factor (VEGF)-targeted treatment (for example, but not limited to, sunitinib, sorafenib, pazopanib, cabozantinib, bevacizumab, axitinib, vatalanib, AV951/tivozanib) administered for the treatment of RCC. Prior programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) treatment in addition to 1 prior VEGF-targeted treatment is allowed.
- At least 1 measurable target lesion according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) meeting the following criteria:
- Lymph node (LN) lesion that measures at least 1 dimension as \>=1.5 centimeter (cm) in the short axis;
- Non-nodal lesion that measures \>=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.
- Male or female participants age \>=18 years (or any age \>=18 years if that age is considered to be an adult per the local jurisdiction) at the time of informed consent
- Karnofsky Performance Status (KPS) of \>=70
- Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than or equal to (\<=) 150/90 millimeters of mercury (mmHg) at Screening and no change in antihypertensive medications within 1 week before Cycle 1/Day 1
- Adequate renal function defined as calculated creatinine clearance \>=30 milliliters per minute (mL/min) per the Cockcroft and Gault formula
- Adequate bone marrow function defined by:
- Absolute neutrophil count (ANC) \>=1500/millimeters cubed (mm\^3) (\>=1.5\*10\^9/Liters \[L\]);
- Platelets \>=100,000/mm\^3 (\>=100\*10\^9/L);
- Hemoglobin \>=9 grams per deciliter (g/dL)
- +6 more criteria
You may not qualify if:
- More than 1 prior VEGF-targeted treatment for advanced RCC
- Participants with Central Nervous System (CNS) metastases are not eligible, unless they have completed local therapy for at least 4 weeks and have discontinued the use of corticosteroids for this indication or are on a tapering regimen of corticosteroids (defined as \<=10 mg prednisolone equivalent) before starting treatment in this study. Any signs (example, radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.
- Active malignancy (except for RCC or definitively treated basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix or bladder) within the past 24 months
- Any anti-cancer treatment (except for radiation therapy) within 21 days, or any investigational agent within 30 days prior to the first dose of study drug; participants should have recovered from any toxicity related to previous anti-cancer treatment to Common Toxicity Criteria (CTC) grade 0 or 1.
- Prior radiation therapy within 21 days prior to the 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
- Known intolerance to study drug (or any of the excipients) and/or known hypersensitivity to rapamycins (example, sirolimus, everolimus, temsirolimus) or any of the excipients
- Participants with proteinuria greater than (\>) 1+ on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein \>=1 g/24 hour will be ineligible.
- Fasting total cholesterol ˃300 mg/dL (or ˃7.75 millimoles \[mmol\]/L) and/or fasting triglycerides level ˃2.5\* the 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 QT corrected (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 or everolimus
- Bleeding or thrombotic disorders or participants at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels (example, carotid artery) 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 6 months prior to the first dose of study drug; history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke, or cardiac arrhythmia associated with significant cardiovascular impairment or left ventricular ejection fraction (LVEF) below the institutional normal range as determined by screening multigated acquisition (MUGA) scan or echocardiogram.
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Eisai Inc.lead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (93)
City of Hope National Medical Center
Duarte, California, 91010, United States
Innovative Clinical Research Institute, LLC
Whittier, California, 90603, United States
Baptist Health Medical Group Oncology, LLC - US Oncology
Miami, Florida, 33143, United States
Optimal Research
Honolulu, Hawaii, 96819, United States
Oklahoma Cancer Specialist and Research Institute , LLC
Tulsa, Oklahoma, 74146, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232, United States
University of Tennessee Medical Center
Knoxville, Tennessee, 37920, United States
Texas Oncology PA - US Oncology
Fort Worth, Texas, 76104, United States
Macquarie University
Macquarie Park, New South Wales, Australia
Northern Cancer Institute, Saint Leonards
Saint Leonards, New South Wales, Australia
Adelaide Cancer Center
Kurralta Park, South Australia, Australia
Sunshine Hospital
Saint Albans, Victoria, Australia
Fiona Stanley Hospital
Murdoch, Western Australia, Australia
Alberta Health Service - Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2, Canada
British Columbia Cancer Agency
Kelowna, British Columbia, V1Y 5L3, Canada
Juravinski Cancer Centre
Hamilton, Ontario, L8V 5C2, Canada
London Health Sciences Centre
London, Ontario, N6A 4L6, Canada
Ottawa Hospital Cancer Centre
Ottawa, Ontario, K1H 8L6, Canada
Sunnybrook Research Institute- University of Toronto
Toronto, Ontario, M4N 3M5, Canada
Sir Mortimer B Davis Jewish General Hospital
Montreal, Quebec, H3T 1E2, Canada
Masarykuv onkologicky ustav
Brno, Czechia
Fakultni nemocnice Olomouc
Olomouc, Czechia
Fakultni nemocnice v Motole
Prague, Czechia
Nemocnice Na Bulovce
Prague, Czechia
Helsingin Yliopistollinen Keskussairaala
Helsinki, Finland
Tampereen yliopistollinen sairaala
Tampere, Finland
Turun Yliopistollinen Keskussairaala
Turku, Finland
Vaasan Keskussairaala
Vaasa, Finland
Alexandra Hospital
Athens, Greece
Metropolitan hospital
Athens, Greece
University General Hospital of Patras
Pátrai, Greece
Interbalkan Medical Center of Thessaloniki
Pylaia, Greece
EUROMEDICA General Clinic of Thessaloniki
Thessaloniki, Greece
Papageorgiou General Hospital of Thessaloniki
Thessaloniki, Greece
IRCCS Istituto Nazionale dei Tumori
Milan, Lombardy, Italy
Presidio Ospedaliero San Donato
Arezzo, 52100, Italy
AORN A Cardarelli
Napoli, Italy
Azienda Ospedaliera San Camillo Forlanini
Roma, 00152, Italy
Leids Universitair Medisch Centrum
Leiden, Netherlands
Hagaziekenhuis
The Hague, Netherlands
MC Haaglanden
The Hague, Netherlands
Szpital Specjalistyczny w Brzozowie
Brzozów, Poland
Copernicus PL Sp. z o.o. Wojewodzkie Centrum Onkologii
Gdansk, Poland
NZOZ Vesalius
Krakow, Poland
SP ZOZ Szpital Uniwersytecki w Krakowie
Krakow, Poland
Centrum Onkologii Ziemi Lubelskiej
Lublin, Poland
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Opolskie Centrum Onkologii
Opole, Poland
Mrukmed. Lekarz Beata Madej-Mruk i Partner. Spolka Partnerska
Rzeszów, Poland
MAGODENT Sp. z o.o. Szpital Elblaska
Warsaw, Poland
Centro Hospitalar E Universitário de Coimbra EPE
Coimbra, Portugal
Centro Hospitalar Lisboa Norte, E.P.E. - Hospital de Santa Maria
Lisbon, Portugal
Champalimaud Cancer Center
Lisbon, Portugal
Centro Hospitalar do Porto - Hospital de Santo António
Porto, Portugal
Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe
Porto, Portugal
Medisprof SRL
Cluj-Napoca, Romania
Prof Dr I Chiricuta Institute of Oncology
Cluj-Napoca, Romania
Oncology Center Sfantul Nectarie
Craiova, Romania
Oncocenter Clinical Oncology
Timișoara, Romania
Altay Regional Oncology Center
Barnaul, Russia
Chelyabinsk Regional Clinical Oncology Dispensary
Chelyabinsk, Russia
Central Clinical Hospital With Polyclinic of President Administration of RF
Moscow, Russia
Moscow City Oncology Hospital #62
Moscow, Russia
Moscow Scientific Research Oncology Institute P.A. Herzen
Moscow, Russia
Federal State Institution Medical Radiology Research Center
Obninsk, Russia
Clinical Oncology Dispensary
Omsk, Russia
Regional Clinical Oncology Hospital
Yaroslavl, Russia
National Cancer Center
Goyang-si, Gyeonggido, South Korea
Chonnam National University Hwasun Hospital
Jeonam, South Korea
Asan Medical Center
Seoul, South Korea
Samsung Medical Center
Seoul, South Korea
Severance Hospital - Yonsei University Health System
Seoul, South Korea
The Catholic University of Korea, Seoul Saint Mary's Hospital
Seoul, South Korea
Hospital Universitario A Coruna
A Coruña, Spain
Hospital Universitario Germans Trias i Pujol
Badalona, Spain
Hospital Clinic de Barcelona
Barcelona, Spain
Hospital de la Santa Creu I Sant Pau
Barcelona, Spain
C.H. Regional Reina Sofia
Córdoba, Spain
ICO l'Hospitalet - Hospital Duran i Reynals
L'Hospitalet de Llobregat, Spain
Hospital Clinico San Carlos
Madrid, 28040, Spain
Hospital Universitario 12 de Octubre
Madrid, Spain
Hospital Universitario Ramon y Cajal
Madrid, Spain
MD Anderson Cancer Center Madrid
Madrid, Spain
Hospital Universitario Son Espases
Palma de Mallorca, Spain
Clinica Universidad Navarra
Pamplona, Spain
Fundacion Instituto Valenciano de Oncologia
Valencia, Spain
China Medical University Hospital
Taichung, Taiwan
Taichung Veterans General Hospital
Taichung, Taiwan
National Taiwan University Hospital
Taipei, Taiwan
Taipei Veterans General Hospital
Taipei, Taiwan
Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom
Christie Hospital
Manchester, United Kingdom
Mount Vernon Hospital
Northwood, United Kingdom
Singleton Hospital
Swansea, United Kingdom
Related Publications (1)
Bergerot C, Young Rha S, Pal S, Koralewski P, Stroyakovskiy D, Alekseev B, Parnis F, Castellano D, Lyun Lee J, Sunela K, Ciuleanu T, Heng D, Glen H, Wang J, Bennett L, Pan J, O'Hara K, Puente J. Health-Related Quality of Life Outcomes With Two Different Starting Doses of Lenvatinib in Combination With Everolimus for Previously Treated Renal Cell Carcinoma. Oncologist. 2023 Jan 18;28(1):59-71. doi: 10.1093/oncolo/oyac142.
PMID: 35881028DERIVED
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 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Masking Details
- Study was initially double-blind.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 22, 2017
First Posted
June 2, 2017
Study Start
August 17, 2017
Primary Completion
February 14, 2020
Study Completion
June 20, 2024
Last Updated
April 1, 2025
Results First Posted
March 5, 2021
Record last verified: 2025-03
Data Sharing
- IPD Sharing
- Will not share