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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02811861




Registration number
NCT02811861
Ethics application status
Date submitted
21/06/2016
Date registered
23/06/2016
Date last updated
30/03/2020

Titles & IDs
Public title
Lenvatinib/Everolimus or Lenvatinib/Pembrolizumab Versus Sunitinib Alone as Treatment of Advanced Renal Cell Carcinoma
Scientific 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)
Secondary ID [1] 0 0
KEYNOTE-581
Secondary ID [2] 0 0
E7080-G000-307
Universal Trial Number (UTN)
Trial acronym
CLEAR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - lenvatinib
Treatment: Drugs - everolimus
Treatment: Drugs - pembrolizumab
Treatment: Drugs - Sunitinib

Experimental: Lenvatinib 18 mg plus everolimus 5 mg - Lenvatinib 18 milligrams (mg) administered orally, once daily, plus everolimus 5 mg administered orally, once daily

Experimental: Lenvatinib 20 mg plus pembrolizumab 200 mg - Lenvatinib 20 mg administered orally, once daily, plus pembrolizumab 200 mg administered intravenously (IV), every 3 weeks

Active Comparator: Sunitinib 50 mg - Sunitinib 50 mg administered orally, once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment


Treatment: Drugs: lenvatinib


Treatment: Drugs: everolimus


Treatment: Drugs: pembrolizumab


Treatment: Drugs: Sunitinib


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS) by independent review
Timepoint [1] 0 0
up to 47 months approximately
Secondary outcome [1] 0 0
Objective response rate (ORR)
Timepoint [1] 0 0
up to approximately 47 months
Secondary outcome [2] 0 0
Overall survival (OS)
Timepoint [2] 0 0
up to approximately 67 months
Secondary outcome [3] 0 0
Number of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Timepoint [3] 0 0
up to approximately 67 months
Secondary outcome [4] 0 0
Number of participants who discontinued treatment due to toxicity
Timepoint [4] 0 0
up to approximately 67 months
Secondary outcome [5] 0 0
Time to treatment failure due to toxicity
Timepoint [5] 0 0
up to approximately 67 months
Secondary outcome [6] 0 0
Health-Related Quality of Life (HRQoL) scores
Timepoint [6] 0 0
up to approximately 47 months
Secondary outcome [7] 0 0
PFS on next-line of therapy (PFS2)
Timepoint [7] 0 0
up to approximately 47 months
Secondary outcome [8] 0 0
PFS by investigator assessment
Timepoint [8] 0 0
up to 47 Months approximately
Secondary outcome [9] 0 0
Model-predicted clearance for lenvatinib and everolimus
Timepoint [9] 0 0
Cycle (C) 1 Day (D) 1; 0.5-4 hours and 6-10 hours postdose; C1D15: predose and 2-12 hours postdose; C2D1: predose, 0.5-4 hours and 6-10 hours postdose; Day 1 of C3, C4, C5, C6: predose (Cycle length = 21 days)
Secondary outcome [10] 0 0
AUC for lenvatinib and everolimus
Timepoint [10] 0 0
C1D1: 0.5-4 hours and 6-10 hours postdose; C1D15: predose and 2-12 hours postdose; C2D1: predose, 0.5-4 hours and 6-10 hours postdose; Day 1 of C3, C4, C5, C6: predose (Cycle length = 21 days)

Eligibility
Key inclusion criteria
- Histological or cytological confirmation of renal cell carcinoma (RCC) with a
clear-cell component

- At least 1 measurable target lesion according to Response Evaluation in Solid Tumors
(RECIST) 1.1

- Karnofsky Performance Status (KPS) of =70

- Adequately controlled blood pressure (BP) with or without antihypertensive
medications, defined as BP =150/90 mmHg at Screening and no change in antihypertensive
medications within 1 week prior to Cycle 1/Day 1 (C1/D1)

- Adequate organ function per blood work
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Participants who have received any systemic anticancer therapy for RCC, including
anti-vascular endothelial growth factor (VEGF) therapy, or any systemic
investigational anticancer agent

- Participants with central nervous system (CNS) metastases are not eligible, unless
they have completed local therapy (eg, 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 (eg,
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

- Received a live vaccine within 30 days of planned start of study treatment

- Participants with urine protein =1 gram/24 hour

- 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)

- 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 below the institutional normal range as determined
by multiple-gated acquisition scan or echocardiogram

- Active infection (any infection requiring systemic treatment)

- Participants known to be positive for Human Immunodeficiency Virus (HIV).

- Known active Hepatitis B (eg, Hepatitis B surface antigen (HBsAg) reactive) or
Hepatitis C (eg, 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 (ie, with use of disease modifying agents,
corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine,
insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is not considered a form of systemic treatment.

- Known intolerance to any of the study drugs (or any of the excipients)

- Participant has had an allogenic tissue/solid organ transplant.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Eastern Clinical Research Unit - Box Hill
Recruitment hospital [2] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [3] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [4] 0 0
Austin Health - Heidelberg
Recruitment hospital [5] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [6] 0 0
Macquarie University Hospital - Macquarie park
Recruitment hospital [7] 0 0
ICON Cancer Foundation - South Brisbane
Recruitment hospital [8] 0 0
Sunshine Hospital - St Albans
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
- Box Hill
Recruitment postcode(s) [4] 0 0
- Heidelberg
Recruitment postcode(s) [5] 0 0
- Hobart
Recruitment postcode(s) [6] 0 0
- Macquarie park
Recruitment postcode(s) [7] 0 0
- South Brisbane
Recruitment postcode(s) [8] 0 0
- St Albans
Recruitment outside Australia
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United States of America
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California
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Nebraska
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North Carolina
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Ohio
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Oregon
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Texas
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Washington
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Austria
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Innsbruck
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Austria
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Linz
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Vienna
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Aalst
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Bonheiden
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Bruxelles
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Hodonice
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Praha 4
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Praha 8
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Hessen
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Ulm
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Bologna
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Meldola
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Milano
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Modena
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Napoli
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Pavia
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Pordenone
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Italy
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Roma
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Italy
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Rome
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Japan
State/province [91] 0 0
Aichi
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Japan
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Akita
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Japan
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Aomori
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Japan
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Chiba
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Japan
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Fukuoka
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Hiroshima
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Hokkaido
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Hyogo
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Kagawa
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Kanagawa
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Kyoto
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Nagasaki
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Tokyo
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Korea, Republic of
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Daegu
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Korea, Republic of
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Goyang-si
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Korea, Republic of
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Seongnam-si
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Korea, Republic of
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Seoul
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Netherlands
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Amsterdam
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Netherlands
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Utrecht
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Poland
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Poland
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Lodz
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Lublin
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Poland
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Szczecin
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Russian Federation
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Moscow
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Russian Federation
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Nizhniy Novgorod
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Russian Federation
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Novosibirsk
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Russian Federation
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Obninsk
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Russian Federation
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Omsk
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Russian Federation
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Tyumen
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Spain
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Cantabria
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Barcelona
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Burgos
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Caceres
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Cordoba
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Spain
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L'Hospitalet de Llobregat,
Country [132] 0 0
Spain
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L'Hospitalet de Llobregat
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Spain
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Lugo
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Spain
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Madrid
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Spain
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Oviedo
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Seville
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Spain
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Valencia
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Switzerland
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Bern
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Switzerland
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Winterthur
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United Kingdom
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Bournemouth
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United Kingdom
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Cardiff
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United Kingdom
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Edinburgh
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United Kingdom
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Glasgow
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Leeds
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London
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United Kingdom
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Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eisai Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a multicenter, randomized, open-label, Phase 3 study to compare the efficacy and
safety of lenvatinib in combination with everolimus (Arm A) or pembrolizumab (Arm B) versus
sunitinib (Arm C) as first-line treatment in participants with advanced renal cell carcinoma.
Trial website
https://clinicaltrials.gov/show/NCT02811861
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
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Email 0 0
Contact person for scientific queries

Summary results
Other publications