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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03553836




Registration number
NCT03553836
Ethics application status
Date submitted
1/06/2018
Date registered
12/06/2018

Titles & IDs
Public title
Safety and Efficacy of Pembrolizumab Compared to Placebo in Resected High-risk Stage II Melanoma (MK-3475-716/KEYNOTE-716)
Scientific title
Adjuvant Therapy With Pembrolizumab Versus Placebo in Resected High-risk Stage II Melanoma: A Randomized, Double-blind Phase 3 Study (KEYNOTE-716)
Secondary ID [1] 0 0
MK-3475-716
Secondary ID [2] 0 0
3475-716
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Pembrolizumab
Other interventions - Placebo

Experimental: Pembrolizumab - Participants receive 200 mg pembrolizumab (2 mg/kg for a maximum of 200 mg in pediatric participants) by intravenous (IV) infusion once every 3 weeks (Q3W; 21-day cycles) for up to 17 cycles (up to \~1 year) in Part 1. Participants who complete the initial treatment of 17 cycles of pembrolizumab and experience disease recurrence may be eligible for re-challenge with pembrolizumab at the same dose and schedule of 200 mg Q3W (21-day cycles) for up to 35 cycles (up to \~2 years) in Part 2.

Placebo comparator: Placebo - Participants receive saline placebo by IV infusion Q3W (21-day cycles) for up to 17 cycles (up to \~1 year) in Part 1. Participants who complete the initial treatment of 17 cycles of placebo and experience disease recurrence may be eligible to switch over to pembrolizumab 200 mg Q3W (21-day cycles) for up to 35 cycles (up to \~2 years) in Part 2.


Treatment: Other: Pembrolizumab
Administered as an intravenous (IV) infusion every 3 weeks (Q3W)

Other interventions: Placebo
Administered as an IV infusion every 3 weeks (Q3W)

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recurrence-free Survival (RFS)
Timepoint [1] 0 0
Up to ~32.7 months
Secondary outcome [1] 0 0
Distant Metastasis-free Survival (DMFS)
Timepoint [1] 0 0
Up to ~9 years
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to ~15 years
Secondary outcome [3] 0 0
Number of Participants Who Experienced at Least One Adverse Event (AE)
Timepoint [3] 0 0
Up to ~19.3 months
Secondary outcome [4] 0 0
Number of Participants Who Discontinued Study Treatment Due to an AE
Timepoint [4] 0 0
Up to ~19.3 months

Eligibility
Key inclusion criteria
Inclusion:

* Has surgically resected and histologically/pathologically confirmed new diagnosis of Stage IIB or IIC cutaneous melanoma per American Joint Committee on Cancer (AJCC) 8th edition guidelines
* Has not been previously treated for melanoma beyond complete surgical resection
* Has =12 weeks between final surgical resection and randomization
* Has no evidence of metastatic disease on imaging as determined by investigator
* Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale or Lansky Play-Performance Scale (LPS) score =50 for participants =16 years old, or a Karnofsky Performance Scale (KPS) score =50 for participants >16 and <18 years old
* Has recovered adequately from toxicity and/or complications from surgery prior to study start
* Female participants must not be pregnant or breastfeeding, and must agree to use contraception during the treatment period and for at least 120 days after the last dose of study treatment if they are women of childbearing potential (WOCBP)
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion:

* Has a known additional malignancy that is progressing or has required active antineoplastic therapy (including hormonal) within the past 5 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
* WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1), anti-Programmed Cell Death Receptor Ligand 1 (PD-L1) or anti-Programmed Cell Death Receptor Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
* Has received prior systemic anti-cancer therapy for melanoma including investigational agents
* Has received a live vaccine within 30 days prior to the first dose of study treatment
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
* Has severe hypersensitivity (=Grade 3) to any excipients of pembrolizumab
* Has an active autoimmune disease that has required systemic treatment in the past 2 years
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
* Has an active infection requiring systemic therapy
* Has a known history of human immunodeficiency virus (HIV) infection
* Has a known history of hepatitis B (defined as hepatitis B surface antigen reactive) or known active hepatitis C virus (defined as hepatitis C virus ribonucleic acid [RNA] [qualitative] is detected) infection
* Has a history of active tuberculosis (Bacillus tuberculosis)
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
* Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
* Has had an allogeneic 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
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,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Melanoma Institute Australia ( Site 0856) - North Sydney
Recruitment hospital [2] 0 0
Westmead Hospital ( Site 0853) - Westmead
Recruitment hospital [3] 0 0
Cairns Base Hospital ( Site 0859) - Cairns
Recruitment hospital [4] 0 0
Tasman Oncology Research Pty Ltd ( Site 0858) - Southport
Recruitment hospital [5] 0 0
Princess Alexandra Hospital ( Site 0857) - Woolloongabba
Recruitment hospital [6] 0 0
Royal Adelaide Hospital ( Site 0861) - Adelaide
Recruitment hospital [7] 0 0
Ashford Cancer Centre Research ( Site 0860) - Kurralta Park
Recruitment hospital [8] 0 0
The Alfred Hospital ( Site 0852) - Melbourne
Recruitment hospital [9] 0 0
Fiona Stanley Hospital ( Site 0851) - Murdoch
Recruitment postcode(s) [1] 0 0
2065 - North Sydney
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4870 - Cairns
Recruitment postcode(s) [4] 0 0
4215 - Southport
Recruitment postcode(s) [5] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [6] 0 0
5000 - Adelaide
Recruitment postcode(s) [7] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [8] 0 0
3004 - Melbourne
Recruitment postcode(s) [9] 0 0
6150 - Murdoch
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
State/province [2] 0 0
California
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United States of America
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Colorado
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United States of America
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Connecticut
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United States of America
State/province [5] 0 0
Florida
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United States of America
State/province [6] 0 0
Georgia
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United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Iowa
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
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Massachusetts
Country [11] 0 0
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Michigan
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Minnesota
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Missouri
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New York
Country [15] 0 0
United States of America
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Ohio
Country [16] 0 0
United States of America
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Oklahoma
Country [17] 0 0
United States of America
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Oregon
Country [18] 0 0
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Pennsylvania
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Tennessee
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Texas
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Virginia
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Washington
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Wisconsin
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Belgium
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Antwerpen
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Belgium
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Bruxelles-Capitale, Region De
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Belgium
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Limburg
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Belgium
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Oost-Vlaanderen
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Belgium
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Vlaams-Brabant
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Brazil
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Parana
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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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Brazil
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Rio de Janeiro
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Canada
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Alberta
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Manitoba
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Canada
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New Brunswick
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Ontario
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Canada
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Quebec
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Chile
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Araucania
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Chile
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Region M. De Santiago
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Chile
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Valparaiso
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Chile
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Antofagasta
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France
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Bouches-du-Rhone
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France
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Cote-d Or
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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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Hauts-de-Seine
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France
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Herault
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France
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Ille-et-Vilaine
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France
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Maine-et-Loire
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France
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Marne
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France
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Rhone
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France
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Somme
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France
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Val-de-Marne
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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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Niedersachsen
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Germany
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Nordrhein-Westfalen
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Germany
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Schleswig-Holstein
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Germany
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Thuringen
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Germany
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Hamburg
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Israel
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Southern
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Israel
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Tell Abib
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Israel
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Afula
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Israel
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Haifa
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Jerusalem
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Israel
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Ramat Gan
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Israel
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Zerifin
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Italy
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Forli-Cesena
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Italy
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Bari
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Italy
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Bergamo
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Genova
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Milano
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Italy
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Napoli
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Padova
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Roma
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Siena
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Japan
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Tokyo
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Kujawsko-pomorskie
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Malopolskie
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Mazowieckie
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Podkarpackie
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Pomorskie
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Poland
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Slaskie
Country [86] 0 0
Poland
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Wielkopolskie
Country [87] 0 0
South Africa
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Eastern Cape
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South Africa
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Gauteng
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South Africa
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Limpopo
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South Africa
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Western Cape
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Spain
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Gipuzkoa
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Spain
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Valenciana, Comunitat
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Sevilla
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Switzerland
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Basel-Stadt
Country [97] 0 0
Switzerland
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Berne
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Switzerland
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Geneve
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Switzerland
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Grisons
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Switzerland
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Sankt Gallen
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Switzerland
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Ticino
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Switzerland
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Vaud
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Switzerland
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Wallis
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Switzerland
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Zurich
Country [105] 0 0
United Kingdom
State/province [105] 0 0
Cambridgeshire
Country [106] 0 0
United Kingdom
State/province [106] 0 0
London, City Of
Country [107] 0 0
United Kingdom
State/province [107] 0 0
Surrey
Country [108] 0 0
United Kingdom
State/province [108] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

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?

Results publications and other study-related documents

TypeCitations or Other Details
Journal Luke JJ, Ascierto PA, Khattak MA, de la Cruz Merin... [More Details]