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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04586231




Registration number
NCT04586231
Ethics application status
Date submitted
9/10/2020
Date registered
14/10/2020

Titles & IDs
Public title
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Scientific title
An Open-label, Randomized, Phase 3 Study of MK-6482 in Combination With Lenvatinib (MK-7902) vs Cabozantinib in Participants With Advanced Renal Cell Carcinoma Who Have Progressed After Prior Anti-PD-1/L1 Therapy
Secondary ID [1] 0 0
MK-6482-011
Secondary ID [2] 0 0
6482-011
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Renal Cell 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 - Belzutifan
Treatment: Drugs - Lenvatinib
Treatment: Drugs - Cabozantinib

Experimental: Belzutifan + Lenvatinib - Belzutifan 120 mg and lenvatinib 20 mg orally once a day

Active comparator: Cabozantinib - Cabozantinib 60 mg orally once a day


Treatment: Drugs: Belzutifan
Immediate-release 40 mg tablet

Treatment: Drugs: Lenvatinib
Capsule available in 4 mg and 10 mg dosages

Treatment: Drugs: Cabozantinib
Tablet available in 20 mg, 40 mg and 60 mg dosages

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

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Timepoint [1] 0 0
Up to approximately 34 months
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 44 months
Secondary outcome [1] 0 0
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Timepoint [1] 0 0
Up to approximately 24 months
Secondary outcome [2] 0 0
Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Timepoint [2] 0 0
Up to approximately 44 months
Secondary outcome [3] 0 0
Number of Participants Who Experienced One or More Adverse Events (AEs)
Timepoint [3] 0 0
Up to approximately 44 months
Secondary outcome [4] 0 0
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Timepoint [4] 0 0
Up to approximately 44 months

Eligibility
Key inclusion criteria
* Unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC).
* Disease progression on or after an anti-programmed cell death-1/ligand 1 (PD-1/L1) therapy as either first or second-line treatment for locally advanced/metastatic RCC or as adjuvant treatment or neoadjuvant/adjuvant with progression on or within 6 months of last dose.
* Measurable disease per RECIST 1.1 criteria as assessed by local study investigator.
* Karnofsky performance status (KPS) score of at least 70% assessed within 10 days before randomization.
* Received no more than 2 prior systemic regimens including: one anti-PD-1/L1 containing adjuvant or neoadjuvant/adjuvant regimens with progression on or within 6 months from the last dose of that regimen OR one or 2 regimens for locoregional/advanced disease
* Received only 1 prior antiPD-1/L1 therapy for adjuvant, neoadjuvant/adjuvant or locally advanced/metastatic RCC.
* A male participant is eligible to participate if he is abstinent from heterosexual intercourse or agrees to use contraception during the intervention period and for at least 7 days after the last dose of belzutifan or lenvatinib in the belzutifan+lenvatinib arm, whichever occurs last, and 23 days after the last dose of cabozantinib.
* A female participant is eligible to participate if they are not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 30 days after the last dose of study intervention in the belzutifan+ lenvatinib arm, or 120 days after the last dose of study intervention in the cabozantinib arm.
* Adequately controlled blood pressure.
* Adequate organ function.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* A pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen.
* Known additional malignancy that is progressing or has required active treatment within the past 3 years except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy.
* Known central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Clinically significant cardiac disease within 6 months of first dose of study intervention.
* Prolongation of QTc interval to >480 ms.
* Symptomatic pleural effusion (e.g.,cough, dyspnea, pleuritic chest pain) that is not clinically stable.
* Pre-existing =Grade 3 gastrointestinal or nongastrointestinal fistula.
* Moderate to severe hepatic impairment.
* History of significant bleeding within 3 months before randomization.
* History of solid organ transplantation.
* Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
* Unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).
* Known hypersensitivity or allergy to the active pharmaceutical ingredients or any component of the study intervention formulations.
* Received colony-stimulating factors [eg, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GMCSF) or recombinant erythropoietin (EPO)] within 28 days before randomization.
* Prior treatment with belzutifan or another hypoxia-inducible factor (HIF)-2a inhibitor.
* Prior treatment with lenvatinib.
* Prior treatment with cabozantinib.
* Currently participating in a study of an investigational agent or using an investigational device.
* Active infection requiring systemic therapy.
* History of human immunodeficiency virus (HIV) infection.
* History of hepatitis B or known active hepatitis C infection.

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)
NSW,SA,VIC
Recruitment hospital [1] 0 0
GenesisCare North Shore ( Site 4011) - St Leonards
Recruitment hospital [2] 0 0
Lyell McEwin Hospital ( Site 4004) - Elizabeth Vale
Recruitment hospital [3] 0 0
Peninsula Health Frankston Hospital ( Site 4001) - Frankston
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 4010) - Melbourne
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [3] 0 0
3199 - Frankston
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
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California
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United States of America
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District of Columbia
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United States of America
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Florida
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Georgia
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United States of America
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Illinois
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United States of America
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Indiana
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United States of America
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Kentucky
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United States of America
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Louisiana
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United States of America
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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United States of America
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Nebraska
Country [15] 0 0
United States of America
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New Jersey
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United States of America
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New York
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North Carolina
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Pennsylvania
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Texas
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United States of America
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Utah
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United States of America
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Vermont
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United States of America
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Virginia
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United States of America
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Washington
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Argentina
State/province [24] 0 0
Buenos Aires
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Argentina
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Santa Fe
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Austria
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Oberosterreich
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Austria
State/province [27] 0 0
Steiermark
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Austria
State/province [28] 0 0
Wien
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Belgium
State/province [29] 0 0
Bruxelles-Capitale, Region De
Country [30] 0 0
Belgium
State/province [30] 0 0
Hainaut
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Belgium
State/province [31] 0 0
Oost-Vlaanderen
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Belgium
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Vlaams-Brabant
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Belgium
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Liege
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Brazil
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Rio Grande Do Norte
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Brazil
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Rio Grande Do Sul
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Brazil
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Sao Paulo
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Canada
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Alberta
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Canada
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British Columbia
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Canada
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New Brunswick
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Canada
State/province [40] 0 0
Ontario
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Canada
State/province [41] 0 0
Quebec
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Chile
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Araucania
Country [43] 0 0
Chile
State/province [43] 0 0
Region M. De Santiago
Country [44] 0 0
Colombia
State/province [44] 0 0
Antioquia
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Colombia
State/province [45] 0 0
Cesar
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Colombia
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Cundinamarca
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Colombia
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Santander
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Czechia
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Brno-mesto
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Czechia
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Jihocesky Kraj
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Czechia
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Praha 4
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Czechia
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Praha 5
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Czechia
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Hradec Kralove
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Finland
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Pirkanmaa
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Finland
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Uusimaa
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Finland
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Varsinais-Suomi
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France
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Ain
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France
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Alpes-Maritimes
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France
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Alsace
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France
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Gironde
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France
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Haute-Garonne
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France
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Haute-Vienne
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France
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Loire-Atlantique
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France
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Maine-et-Loire
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France
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Paris
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Germany
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Baden-Wurttemberg
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Germany
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Bayern
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Germany
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Hessen
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Germany
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Nordrhein-Westfalen
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Germany
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Saarland
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Germany
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Sachsen-Anhalt
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Germany
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Thuringen
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Germany
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Berlin
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Greece
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Achaia
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Greece
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Attiki
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Greece
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Thessaloniki
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Ireland
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Dublin
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Italy
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Forli-Cesena
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Italy
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Milano
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Italy
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Torino
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Italy
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Arezzo
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Italy
State/province [81] 0 0
Bari
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Italy
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Pavia
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Italy
State/province [83] 0 0
Roma
Country [84] 0 0
Italy
State/province [84] 0 0
Terni
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Italy
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Verona
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Japan
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Aichi
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Japan
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Chiba
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Hokkaido
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Japan
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Hyogo
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Japan
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Kanagawa
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Japan
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Nara
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Japan
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Osaka
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Japan
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Shizuoka
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Japan
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Tokyo
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Japan
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Fukuoka
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Japan
State/province [96] 0 0
Niigata
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Korea, Republic of
State/province [97] 0 0
Jeonranamdo
Country [98] 0 0
Korea, Republic of
State/province [98] 0 0
Seoul
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Netherlands
State/province [99] 0 0
Fryslan
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Netherlands
State/province [100] 0 0
Limburg
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Netherlands
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Noord-Brabant
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Netherlands
State/province [102] 0 0
Noord-Holland
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Netherlands
State/province [103] 0 0
Zuid-Holland
Country [104] 0 0
Netherlands
State/province [104] 0 0
Utrecht
Country [105] 0 0
Poland
State/province [105] 0 0
Kujawsko-pomorskie
Country [106] 0 0
Poland
State/province [106] 0 0
Malopolskie
Country [107] 0 0
Poland
State/province [107] 0 0
Mazowieckie
Country [108] 0 0
Poland
State/province [108] 0 0
Wielkopolskie
Country [109] 0 0
Romania
State/province [109] 0 0
Cluj
Country [110] 0 0
Romania
State/province [110] 0 0
Dolj
Country [111] 0 0
Russian Federation
State/province [111] 0 0
Ivanovskaya Oblast
Country [112] 0 0
Russian Federation
State/province [112] 0 0
Moskovskaya Oblast
Country [113] 0 0
Russian Federation
State/province [113] 0 0
Moskva
Country [114] 0 0
Russian Federation
State/province [114] 0 0
Volgogradskaya Oblast
Country [115] 0 0
Russian Federation
State/province [115] 0 0
Yaroslavskaya Oblast
Country [116] 0 0
Spain
State/province [116] 0 0
La Coruna
Country [117] 0 0
Spain
State/province [117] 0 0
Madrid, Comunidad De
Country [118] 0 0
Spain
State/province [118] 0 0
Barcelona
Country [119] 0 0
Spain
State/province [119] 0 0
Madrid
Country [120] 0 0
Spain
State/province [120] 0 0
Sevilla
Country [121] 0 0
Switzerland
State/province [121] 0 0
Geneve
Country [122] 0 0
Switzerland
State/province [122] 0 0
Grisons
Country [123] 0 0
Switzerland
State/province [123] 0 0
Ticino
Country [124] 0 0
Switzerland
State/province [124] 0 0
Zurich
Country [125] 0 0
United Kingdom
State/province [125] 0 0
Aberdeen City
Country [126] 0 0
United Kingdom
State/province [126] 0 0
Bath And North East Somerset
Country [127] 0 0
United Kingdom
State/province [127] 0 0
England
Country [128] 0 0
United Kingdom
State/province [128] 0 0
Essex
Country [129] 0 0
United Kingdom
State/province [129] 0 0
London, City Of
Country [130] 0 0
United Kingdom
State/province [130] 0 0
Somerset
Country [131] 0 0
United Kingdom
State/province [131] 0 0
Wales

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Eisai Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.