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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04003636




Registration number
NCT04003636
Ethics application status
Date submitted
28/06/2019
Date registered
1/07/2019

Titles & IDs
Public title
Pembrolizumab (MK-3475) Plus Gemcitabine/Cisplatin Versus Placebo Plus Gemcitabine/Cisplatin for First-Line Advanced and/or Unresectable Biliary Tract Carcinoma (BTC) (MK-3475-966/KEYNOTE-966)
Scientific title
A Phase 3 Randomized, Double Blind Study of Pembrolizumab Plus Gemcitabine/Cisplatin Versus Placebo Plus Gemcitabine/Cisplatin as First-Line Therapy in Participants With Advanced and/or Unresectable Biliary Tract Carcinoma
Secondary ID [1] 0 0
MK-3475-966
Secondary ID [2] 0 0
3475-966
Universal Trial Number (UTN)
Trial acronym
KEYNOTE-966
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Biliary Tract 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: Other - Pembrolizumab
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Cisplatin
Treatment: Drugs - Placebo

Experimental: Arm A (Pembrolizumab+Gemcitabine+Cisplatin) - Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.

Placebo comparator: Arm B (Placebo+Gemcitabine+Cisplatin) - Placebo to Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.


Treatment: Other: Pembrolizumab
Pembrolizumab by intravenous (IV) infusion

Treatment: Drugs: Gemcitabine
Gemcitabine by IV infusion

Treatment: Drugs: Cisplatin
Cisplatin by IV infusion

Treatment: Drugs: Placebo
Placebo to pembrolizumab

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

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Up to approximately 38 months
Secondary outcome [1] 0 0
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (BICR)
Timepoint [1] 0 0
Up to approximately 26 months
Secondary outcome [2] 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 [2] 0 0
Up to approximately 26 months
Secondary outcome [3] 0 0
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
Timepoint [3] 0 0
Up to approximately 38 months
Secondary outcome [4] 0 0
Number of Participants Who Experience One or More Adverse Events (AE)
Timepoint [4] 0 0
Up to approximately 38 months
Secondary outcome [5] 0 0
Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)
Timepoint [5] 0 0
Up to approximately 38 months

Eligibility
Key inclusion criteria
Inclusion Criteria

* Has histologically confirmed diagnosis of advanced (metastatic) and/or unresectable (locally advanced) biliary tract cancer (intra-or extrahepatic cholangiocarcinoma or gallbladder cancer)
* Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1), as determined by the site investigator
* Participants with a history of hepatitis B or hepatitis C can be enrolled if they meet study criteria
* Is able to provide archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion
* Has a life expectancy of greater than 3 months
* Has adequate organ function
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

* Has had previous systemic therapy for advanced (metastatic) or unresectable (locally advanced) biliary tract cancer (intra-or extra hepatic cholangiocarcinoma or gallbladder cancer)
* Has ampullary cancer
* Has small cell cancer, neuroendocrine tumors, lymphoma, sarcoma, mixed tumor histology and/or mucinous cystic neoplasms
* Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti- programmed cell death ligand 1 or 2 (anti-PD-L1, anti-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 a known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis, as assessed by local site investigator
* 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
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,VIC
Recruitment hospital [1] 0 0
Liverpool Hospital ( Site 0707) - Liverpool
Recruitment hospital [2] 0 0
Mid North Coast Cancer Institute ( Site 0708) - Port Macquarie
Recruitment hospital [3] 0 0
Gallipoli Medical Research Foundation ( Site 0705) - Brisbane
Recruitment hospital [4] 0 0
Eastern Health ( Site 0704) - Box Hill
Recruitment hospital [5] 0 0
Western Health-Sunshine Hospital ( Site 0709) - St Albans
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [3] 0 0
4120 - Brisbane
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
3021 - St Albans
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
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United States of America
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Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
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United States of America
State/province [8] 0 0
Oklahoma
Country [9] 0 0
United States of America
State/province [9] 0 0
Oregon
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
Argentina
State/province [12] 0 0
Caba
Country [13] 0 0
Argentina
State/province [13] 0 0
Tucuman
Country [14] 0 0
Argentina
State/province [14] 0 0
La Rioja
Country [15] 0 0
Belgium
State/province [15] 0 0
Antwerpen
Country [16] 0 0
Belgium
State/province [16] 0 0
Bruxelles-Capitale, Region De
Country [17] 0 0
Belgium
State/province [17] 0 0
Hainaut
Country [18] 0 0
Belgium
State/province [18] 0 0
Liege
Country [19] 0 0
Belgium
State/province [19] 0 0
Oost-Vlaanderen
Country [20] 0 0
Belgium
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Vlaams-Brabant
Country [21] 0 0
Brazil
State/province [21] 0 0
Minas Gerais
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Brazil
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Rio Grande Do Sul
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Brazil
State/province [23] 0 0
Rio de Janeiro
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Brazil
State/province [24] 0 0
Sao Paulo
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Canada
State/province [25] 0 0
Alberta
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario
Country [27] 0 0
Canada
State/province [27] 0 0
Quebec
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Chile
State/province [28] 0 0
Araucania
Country [29] 0 0
Chile
State/province [29] 0 0
Coquimbo
Country [30] 0 0
Chile
State/province [30] 0 0
Lbtdr Gen Bernardo O Higgins
Country [31] 0 0
Chile
State/province [31] 0 0
Region M. De Santiago
Country [32] 0 0
China
State/province [32] 0 0
Anhui
Country [33] 0 0
China
State/province [33] 0 0
Beijing
Country [34] 0 0
China
State/province [34] 0 0
Chongqing
Country [35] 0 0
China
State/province [35] 0 0
Fujian
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China
State/province [36] 0 0
Guangdong
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China
State/province [37] 0 0
Hainan
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China
State/province [38] 0 0
Heilongjiang
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China
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Hunan
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China
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Jiangsu
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China
State/province [41] 0 0
Jilin
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China
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Shanghai
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China
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Shanxi
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China
State/province [44] 0 0
Sichuan
Country [45] 0 0
China
State/province [45] 0 0
Tianjin
Country [46] 0 0
China
State/province [46] 0 0
Zhejiang
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France
State/province [47] 0 0
Gironde
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France
State/province [48] 0 0
Hauts-de-Seine
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France
State/province [49] 0 0
Herault
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France
State/province [50] 0 0
Ille-et-Vilaine
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France
State/province [51] 0 0
Puy-de-Dome
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France
State/province [52] 0 0
Val-de-Marne
Country [53] 0 0
Germany
State/province [53] 0 0
Baden-Wurttemberg
Country [54] 0 0
Germany
State/province [54] 0 0
Bayern
Country [55] 0 0
Germany
State/province [55] 0 0
Hessen
Country [56] 0 0
Germany
State/province [56] 0 0
Niedersachsen
Country [57] 0 0
Germany
State/province [57] 0 0
Nordrhein-Westfalen
Country [58] 0 0
Germany
State/province [58] 0 0
Sachsen-Anhalt
Country [59] 0 0
Germany
State/province [59] 0 0
Sachsen
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Germany
State/province [60] 0 0
Berlin
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Germany
State/province [61] 0 0
Hamburg
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Hong Kong
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Hong Kong
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Hong Kong
State/province [63] 0 0
Kowloon
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Ireland
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Cork
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Ireland
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Dublin
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Petah Tikva
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Israel
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Tel Aviv
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Italy
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Abruzzo
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Italy
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Bologna
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Italy
State/province [72] 0 0
Catania
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Italy
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Milano
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Italy
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Pisa
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Italy
State/province [75] 0 0
Roma
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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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Japan
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Hyogo
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Japan
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Kagawa
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Japan
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Kanagawa
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Japan
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Osaka
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Japan
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Tokyo
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Japan
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Fukuoka
Country [85] 0 0
Japan
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Kyoto
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Korea, Republic of
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Jeonranamdo
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Korea, Republic of
State/province [87] 0 0
Kyonggi-do
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Korea, Republic of
State/province [88] 0 0
Taegu-Kwangyokshi
Country [89] 0 0
Korea, Republic of
State/province [89] 0 0
Taejon-Kwangyokshi
Country [90] 0 0
Korea, Republic of
State/province [90] 0 0
Seoul
Country [91] 0 0
Malaysia
State/province [91] 0 0
Johor
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Malaysia
State/province [92] 0 0
Kuala Lumpur
Country [93] 0 0
Malaysia
State/province [93] 0 0
Pulau Pinang
Country [94] 0 0
Malaysia
State/province [94] 0 0
Wilayah Persekutuan Putrajaya
Country [95] 0 0
Netherlands
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Limburg
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Netherlands
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Noord-Holland
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Netherlands
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Zuid-Holland
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Netherlands
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Groningen
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Netherlands
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Utrecht
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New Zealand
State/province [100] 0 0
Auckland
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Spain
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Asturias
Country [102] 0 0
Spain
State/province [102] 0 0
Barcelona
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Spain
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Madrid
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Spain
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Malaga
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Taiwan
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Taipei
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Taiwan
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Kaohsiung
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Taiwan
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Taichung
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Taiwan
State/province [108] 0 0
Tainan
Country [109] 0 0
Taiwan
State/province [109] 0 0
Taoyuan
Country [110] 0 0
Thailand
State/province [110] 0 0
Krung Thep Maha Nakhon
Country [111] 0 0
Thailand
State/province [111] 0 0
Ubon Ratchathani
Country [112] 0 0
Thailand
State/province [112] 0 0
Chiang Mai
Country [113] 0 0
Thailand
State/province [113] 0 0
Khon Kaen
Country [114] 0 0
Thailand
State/province [114] 0 0
Udon Thani
Country [115] 0 0
Turkey
State/province [115] 0 0
Adana
Country [116] 0 0
Turkey
State/province [116] 0 0
Ankara
Country [117] 0 0
Turkey
State/province [117] 0 0
Istanbul
Country [118] 0 0
Turkey
State/province [118] 0 0
Izmir
Country [119] 0 0
Turkey
State/province [119] 0 0
Kayseri
Country [120] 0 0
United Kingdom
State/province [120] 0 0
Aberdeen City
Country [121] 0 0
United Kingdom
State/province [121] 0 0
London, City Of
Country [122] 0 0
United Kingdom
State/province [122] 0 0
Surrey
Country [123] 0 0
United Kingdom
State/province [123] 0 0
Belfast
Country [124] 0 0
United Kingdom
State/province [124] 0 0
Coventry
Country [125] 0 0
United Kingdom
State/province [125] 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 Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z... [More Details]