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AzTrials

Renal Cell CarcinomaPhase 2NCT03173560

Trial to Assess Safety and Efficacy of Lenvatinib (18 mg vs. 14 mg) in Combination With Everolimus in Participants With Renal Cell Carcinoma

A Phase 2 study testing lenvatinib and everolimus in people with Renal Cell Carcinoma, run by Eisai Inc. at 93 sites in 16 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… 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 and everolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
343 participants
Where
93 sitesin 16 countries
Study dates
17 Aug 2017to 20 Jun 2024
Phase
Phase 2
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 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;
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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.
  • 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)
  • Adequate blood coagulation function defined by International Normalized Ratio (INR) <=1.5 (except for participants on warfarin therapy where INR must be <=3.0 prior to randomization)
  • Adequate liver function defined by:
  • Total bilirubin <=1.5 times the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert's syndrome;
  • Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) <=3* the ULN (in the case of liver metastases <=5* the ULN). Participants with bone metastases with ALP values greater than 3 times can be included.
  • Participant must voluntarily agree to provide written informed consent
  • Participant must be willing and able to comply with all aspects of the protocol

Who cannot join

  • 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
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  • 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.
  • Active infection (any infection requiring systemic treatment)
  • Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study
  • Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [β-hCG] (or human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 International Units per Liter [IU/L] or equivalent units of β-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 (Note: all females will be considered to be of childbearing potential unless they are postmenopausal [amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause] or have been sterilized surgically [that is, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing].):
  • do not agree to use a highly effective method of contraception for the entire study period and for up to 8 weeks after study drug 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) (Note: Participants must be on a stable dose of the same oral hormonal contraceptive product for at least 4 weeks before dosing with study drug and for the duration of the study.) OR
  • do not have a vasectomized partner with confirmed azoospermia
  • For sites outside of the European Union, 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.

Trial locations and contacts

93 sites in 16 countries.

93 sites in 16 countries

Spain13 sites

  • Hospital Universitario A Coruna

    A Coruña

  • Hospital Universitario Germans Trias i Pujol

    Badalona

  • Hospital Clinic de Barcelona

    Barcelona

  • Hospital de la Santa Creu I Sant Pau

    Barcelona

  • C.H. Regional Reina Sofia

    Córdoba

  • ICO l'Hospitalet - Hospital Duran i Reynals

    L'Hospitalet de Llobregat

  • Hospital Clinico San Carlos

    Madrid, 28040

  • Hospital Universitario 12 de Octubre

    Madrid

  • Hospital Universitario Ramon y Cajal

    Madrid

  • MD Anderson Cancer Center Madrid

    Madrid

  • Hospital Universitario Son Espases

    Palma de Mallorca

  • Clinica Universidad Navarra

    Pamplona

  • Fundacion Instituto Valenciano de Oncologia

    Valencia

Other trials in Spain

United States8 sites

  • City of Hope National Medical Center

    Duarte, California, 91010

  • Texas Oncology PA - US Oncology

    Fort Worth, Texas, 76104

  • Optimal Research

    Honolulu, Hawaii, 96819

  • University of Tennessee Medical Center

    Knoxville, Tennessee, 37920

  • Baptist Health Medical Group Oncology, LLC - US Oncology

    Miami, Florida, 33143

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15232

  • Oklahoma Cancer Specialist and Research Institute , LLC

    Tulsa, Oklahoma, 74146

  • Innovative Clinical Research Institute, LLC

    Whittier, California, 90603

Other trials in United States

Poland8 sites

  • Szpital Specjalistyczny w Brzozowie

    Brzozów

  • Copernicus PL Sp. z o.o. Wojewodzkie Centrum Onkologii

    Gdansk

  • NZOZ Vesalius

    Krakow

  • SP ZOZ Szpital Uniwersytecki w Krakowie

    Krakow

  • Centrum Onkologii Ziemi Lubelskiej

    Lublin

  • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Opolskie Centrum Onkologii

    Opole

  • Mrukmed. Lekarz Beata Madej-Mruk i Partner. Spolka Partnerska

    Rzeszów

  • MAGODENT Sp. z o.o. Szpital Elblaska

    Warsaw

Other trials in Poland

Russia8 sites

  • Altay Regional Oncology Center

    Barnaul

  • Chelyabinsk Regional Clinical Oncology Dispensary

    Chelyabinsk

  • Central Clinical Hospital With Polyclinic of President Administration of RF

    Moscow

  • Moscow City Oncology Hospital #62

    Moscow

  • Moscow Scientific Research Oncology Institute P.A. Herzen

    Moscow

  • Federal State Institution Medical Radiology Research Center

    Obninsk

  • Clinical Oncology Dispensary

    Omsk

  • Regional Clinical Oncology Hospital

    Yaroslavl

Other trials in Russia

Canada7 sites

  • Alberta Health Service - Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • Juravinski Cancer Centre

    Hamilton, Ontario, L8V 5C2

  • British Columbia Cancer Agency

    Kelowna, British Columbia, V1Y 5L3

  • London Health Sciences Centre

    London, Ontario, N6A 4L6

  • Sir Mortimer B Davis Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • Ottawa Hospital Cancer Centre

    Ottawa, Ontario, K1H 8L6

  • Sunnybrook Research Institute- University of Toronto

    Toronto, Ontario, M4N 3M5

Other trials in Canada

Greece6 sites

  • Alexandra Hospital

    Athens

  • Metropolitan hospital

    Athens

  • University General Hospital of Patras

    Pátrai

  • Interbalkan Medical Center of Thessaloniki

    Pylaia

  • EUROMEDICA General Clinic of Thessaloniki

    Thessaloniki

  • Papageorgiou General Hospital of Thessaloniki

    Thessaloniki

Other trials in Greece

South Korea6 sites

  • National Cancer Center

    Goyang-si, Gyeonggido

  • Chonnam National University Hwasun Hospital

    Jeonam

  • Asan Medical Center

    Seoul

  • Samsung Medical Center

    Seoul

  • Severance Hospital - Yonsei University Health System

    Seoul

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

    Seoul

Other trials in South Korea

Australia5 sites

  • Adelaide Cancer Center

    Kurralta Park, South Australia

  • Macquarie University

    Macquarie Park, New South Wales

  • Fiona Stanley Hospital

    Murdoch, Western Australia

  • Sunshine Hospital

    Saint Albans, Victoria

  • Northern Cancer Institute, Saint Leonards

    Saint Leonards, New South Wales

Other trials in Australia

Portugal5 sites

  • Centro Hospitalar E Universitário de Coimbra EPE

    Coimbra

  • Centro Hospitalar Lisboa Norte, E.P.E. - Hospital de Santa Maria

    Lisbon

  • Champalimaud Cancer Center

    Lisbon

  • Centro Hospitalar do Porto - Hospital de Santo António

    Porto

  • Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe

    Porto

Other trials in Portugal

Czechia4 sites

  • Masarykuv onkologicky ustav

    Brno

  • Fakultni nemocnice Olomouc

    Olomouc

  • Fakultni nemocnice v Motole

    Prague

  • Nemocnice Na Bulovce

    Prague

Other trials in Czechia

Finland4 sites

  • Helsingin Yliopistollinen Keskussairaala

    Helsinki

  • Tampereen yliopistollinen sairaala

    Tampere

  • Turun Yliopistollinen Keskussairaala

    Turku

  • Vaasan Keskussairaala

    Vaasa

Other trials in Finland

Italy4 sites

  • Presidio Ospedaliero San Donato

    Arezzo, 52100

  • IRCCS Istituto Nazionale dei Tumori

    Milan, Lombardy

  • AORN A Cardarelli

    Naples

  • Azienda Ospedaliera San Camillo Forlanini

    Roma, 00152

Other trials in Italy

Romania4 sites

  • Medisprof SRL

    Cluj-Napoca

  • Prof Dr I Chiricuta Institute of Oncology

    Cluj-Napoca

  • Oncology Center Sfantul Nectarie

    Craiova

  • Oncocenter Clinical Oncology

    Timișoara

Other trials in Romania

Taiwan4 sites

  • China Medical University Hospital

    Taichung

  • Taichung Veterans General Hospital

    Taichung

  • National Taiwan University Hospital

    Taipei

  • Taipei Veterans General Hospital

    Taipei

Other trials in Taiwan

United Kingdom4 sites

  • Beatson West of Scotland Cancer Centre

    Glasgow

  • Christie Hospital

    Manchester

  • Mount Vernon Hospital

    Northwood

  • Singleton Hospital

    Swansea

Other trials in United Kingdom

Netherlands3 sites

  • Leids Universitair Medisch Centrum

    Leiden

  • Hagaziekenhuis

    The Hague

  • MC Haaglanden

    The Hague

Other trials in Netherlands

About this study

Official title: 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

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).

Being tested
lenvatinib, everolimus
Keywords
Renal Cell Carcinoma, lenvatinib, everolimus, E7080, VEGF-targeted treatment
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 NCT03173560
Study groupRoleWhat they receive
Lenvatinib 14 mg plus everolimus 5 mgExperimentalParticipants 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.
Receives: Drug: lenvatinib; Drug: everolimus
Lenvatinib 18 mg plus everolimus 5 mgExperimentalParticipants 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.
Receives: Drug: lenvatinib; Drug: everolimus

What is being measured

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

  1. 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.

    Measured: At Week 24

  2. 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.

    Measured: Up to Week 24

Secondary outcomes (16)

  1. Progression-free Survival (PFS)

    PFS was defined as the time from the date of randomization to the date of the first documentation of PD by investigator assessment or date of death, whichever occurred first according to RECIST v1.1. PD: at least 20% increase (including an absolute increase of at least 5 millimeter [mm]) in the sum of diameter (SOD) of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. Median PFS was analyzed using the Kaplan-Meier product-limit estimates for each treatment group and presented with 2-sided 95% confidence interval (CI). As pre-specified in the protocol, data for this secondary outcome measure was collected and analyzed till the primary analysis only.

    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 date of data cutoff for the primary analysis (up to 29 months)

  2. Objective Response Rate (ORR)

    ORR was defined as the percentage of participants with a BOR of CR or PR at the at the end of treatment based on investigator assessment according to RECIST v1.1. 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 <10 mm. 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. As pre-specified in the protocol, data for this secondary outcome measure was collected and analyzed till the primary analysis only.

    Measured: 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)

  3. Number of Participants With TEAEs and Serious TEAEs

    TEAEs were defined as those adverse events (AEs) that occurred (or worsened, if present at Baseline) after the first dose of study drug through 28 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 serious adverse event (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.

    Measured: From date of first dose of study drug up to 28 days after last dose of study drug (up to 71 months)

  4. Percentage of Participants Who Discontinued Treatment Due to Toxicity

    Percentage of participants who discontinued treatment due to toxicity, defined as the percentage of participants who discontinued study treatment due to TEAEs. Toxicity (except hypertension and non-infectious pneumonitis) was assessed according to NCI-CTCAE v4.03.

    Measured: From date of first dose of study drug up to 28 days after last dose of study drug (up to 71 months)

  5. Time to Treatment Failure Due to Toxicity

    Time to treatment failure due to toxicity was defined as the time from the date of randomization to the date that a participant discontinued study treatment due to TEAEs. Toxicity (except hypertension and non-infectious pneumonitis) was assessed according to CTCAE v4.03. As planned, data for this secondary outcome measure was collected and analyzed till the primary analysis only.

    Measured: 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)

  6. Plasma Concentration of Lenvatinib

    PK sparse sampling was performed. As planned, the post-dose plasma sample was collected anytime between 0.5 to 4 hours at Cycle 1 Days 1 and 15, between 6 to 10 hours at Cycle 1 Days 1 and 15, and between 2 to 12 hours at Cycle 2 Day 1. Only one sample was collected for each post-dose category between specified timepoints.

    Measured: Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose, 0.5-4 hours and 6-10 hours post-dose; Cycle 2 Day 1: pre-dose and 2-12 hours post-dose (each cycle length =28 days)

  7. Whole Blood Concentration of Everolimus

    PK sparse sampling was performed. As planned, the post-dose whole blood sample was collected anytime between 0.5 to 4 hours at Cycle 1 Days 1 and 15, between 6 to 10 hours at Cycle 1 Days 1 and 15, and between 2 to 12 hours at Cycle 2 Day 1. Only one sample was collected for each post-dose category between specified timepoints.

    Measured: Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose, 0.5-4 hours and 6-10 hours post-dose; Cycle 2 Day 1: pre-dose and 2-12 hours post-dose (each cycle length =28 days)

  8. Model Predicted Apparent Total Clearance (CL/F) for Lenvatinib Alone and When Coadministration With Everolimus in Renal Cell Carcinoma (RCC) Participants to Assess Drug-Drug Interaction

    Sparse PK samples were collected and analyzed using a population PK approach to estimate PK parameters. The lenvatinib concentration data was pooled from studies E7080 -G000-205 (NCT01136733), E7080-M001-221 (NCT02915783), E7080-J081-112 (NCT02454478) and from current study E7080-G000-218 (NCT03173560). A previously developed 3-compartment PK model for lenvatinib was fitted to the pooled dataset. Individual lenvatinib CL/F value was derived from the final PK model. The outcome measure was assessed for lenvatinib 18 mg dose only.

    Measured: Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose, 0.5-4 hours and 6-10 hours post-dose; Cycle 2 Day 1: pre-dose and 2-12 hours post-dose (each cycle length =28 days)

  9. Model Predicted Dose Normalized Area Under the Plasma Concentration-time Curve (AUC) for Lenvatinib Alone and When Coadministration With Everolimus in RCC Participants to Assess Drug-Drug Interaction

    Sparse PK samples were collected and analyzed using a population PK approach to estimate PK parameters. The lenvatinib concentration data was pooled from studies E7080 -G000-205 (NCT01136733), E7080-M001-221 (NCT02915783), E7080-J081-112 (NCT02454478) and from current study E7080-G000-218 (NCT03173560). A previously developed 3-compartment PK model for lenvatinib was fitted to the pooled dataset. Individual lenvatinib AUC at steady state based on the starting dose was derived as a function of starting dose from the final PK model. The outcome measure was assessed for lenvatinib 18 mg dose only.

    Measured: Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose, 0.5-4 hours and 6-10 hours post-dose; Cycle 2 Day 1: pre-dose and 2-12 hours post-dose (each cycle length =28 days)

  10. Model Predicted CL/F for Everolimus Alone and When Coadministration With Lenvatinib in RCC Participants to Assess Drug-Drug Interaction

    Sparse PK samples were collected and analyzed using a population PK approach to estimate PK parameters. The everolimus concentration data was pooled from studies E7080-G000-205 (NCT01136733), E7080-M001-221 (NCT02915783), E7080-J081-112 (NCT02454478) or from current study E7080-G000-218 (NCT03173560). A previously developed 3-compartment PK model for everolimus was fitted to the pooled dataset. Individual everolimus CL/F value was derived from the final PK model.

    Measured: Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose, 0.5-4 hours and 6-10 hours post-dose; Cycle 2 Day 1: pre-dose and 2-12 hours post-dose (each cycle length =28 days)

  11. Model Predicted Dose Normalized AUC for Everolimus Alone and When Coadministration With Lenvatinib in RCC Participants to Assess Drug-Drug Interaction

    Sparse PK samples were collected and analyzed using a population PK approach to estimate PK parameters. The everolimus concentration data was pooled from studies E7080-G000-205 (NCT01136733), E7080-M001-221 (NCT02915783), E7080-J081-112 (NCT02454478) or from current study E7080-G000-218 (NCT03173560). A previously developed 3-compartment PK model for everolimus was fitted to the pooled dataset. Individual everolimus AUC at steady state based on the starting dose was derived as a function of starting dose from the final PK model.

    Measured: Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose, 0.5-4 hours and 6-10 hours post-dose; Cycle 2 Day 1: pre-dose and 2-12 hours post-dose (each cycle length =28 days)

  12. Overall Survival (OS)

    OS was defined as the time from the date of randomization until the date of death from any cause. In the absence of confirmation of death, participants will be censored either at the date that the participant was last known to be alive or the date of data cutoff for the primary analysis, whichever comes earlier. Median OS was to be calculated using Kaplan-Meier estimate and presented with 2-sided 95% confidence interval. As pre-specified in the protocol, data for this secondary outcome measure was collected and analyzed till the primary analysis only.

    Measured: From the date of randomization until the date of death from any cause, or up to date of data cut off for the primary analysis (up to 29 months)

  13. 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. As pre-specified in the protocol, data for this secondary outcome measure was collected and analyzed till the primary analysis only.

    Measured: At baseline (prior to first dose of study drug), on Day 1 of each subsequent cycle (cycle length =28 days), and at the Off-treatment visit (up to 29 months)

  14. HRQoL Assessed by European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 Scores

    The EORT QLQ-C30 consisted of 30 questions comprising 9 multiple-item scales and 6 single items. Multiple-item scales of QLQ-C30 consisted of 5 functional scales (physical, role, emotional, cognitive, and social) and 3 symptom scales (fatigue, nausea and vomiting, pain) and a global health status/QOL score. Six single-item scales of QLQ-C30 involved dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties. First 28 questions used a 4-point scale (1 = Not at all to 4 = Very much); and last 2 questions used a 7-point scale (1 = Very poor to 7 = Excellent). Scores for all scales range from 0 to 100. For the overall HRQoL and functioning scales, a higher score was correlated with better HRQoL, whereas a higher score for symptom scales represented worse HRQoL. As pre-specified in protocol, data for secondary outcome measure was collected and analyzed till primary analysis only.

    Measured: At baseline (prior to first dose of study drug), on Day 1 of each subsequent cycle (cycle length =28 days), and at the Off-treatment visit (up to 29 months)

  15. HRQoL Assessed by European Quality of Life (EuroQol) Five-Dimensional, 3-Level (EQ-5D-3L) Index Score and Visual Analogue Scale (VAS)

    The EQ-5D-3L is a health profile questionnaire assessing quality of life along 5 dimensions. Participants rate 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranges from 5-15 with "5" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions. The EQ-5D index was calculated by applying preference-based weights (tariffs) to the scores of the five health state dimensions. Index values can range from -1 to 1, with 0 representing a health state equivalent to death and 1 representing perfect health. EQ-5D-3L also included an EQ visual analogue scale (VAS) that ranges between 100 (best imaginable health) and 0 (worst imaginable health). Decrease from baseline in EQ-5D-3L signifies improvement. Total index EQ-5D-3L summary score was weighted with a range of -0.594 (worst) to 1.0 (best).

    Measured: At baseline (prior to first dose of study drug), on Day 1 of each subsequent cycle (cycle length =28 days), and at the Off-treatment visit (up to 29 months)

  16. Progression-free Survival After Next Line of Therapy (PFS2)

    PFS2, defined as the time from randomization to the date of PD after next line of therapy or death from any cause, whichever occurred first based on investigator assessment according to RECIST v1.1. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. Median PFS2 was analyzed using the Kaplan-Meier product-limit estimates for each treatment group and presented with 2-sided 95% CI. As pre-specified in protocol, data for this secondary outcome measure was collected and analyzed till the primary analysis only.

    Measured: From the time of randomization to the date of PD after next line of therapy or death from any cause or the date of data cutoff for the primary analysis, whichever occurs first (up to 29 months)

Timeline

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

  1. First posted2 Jun 2017
  2. Study start17 Aug 2017
  3. Primary completion14 Feb 2020
  4. Study completion20 Jun 2024

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
343 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03173560
Sponsor's protocol ID
E7080-G000-218
Other IDs
2016-002778-11, 2016
Status last verified
Mar 2025
First submitted
22 May 2017
Last updated
1 Apr 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 35881028

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing lenvatinib and everolimus in people with Renal Cell Carcinoma, run by Eisai Inc. at 93 sites in 16 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 21 inclusion and 26 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: finished, as of the sponsor's last update on 1 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 93 sites in Spain, United States, Poland, Russia, Canada and 11 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 5 Mar 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?

Objective Response Rate at Week 24 (ORR24W) (time frame: At Week 24). The study lists 2 primary outcomes in all. 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 NCT03173560, which also lists 1 linked publication.

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 1 Apr 2025.

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