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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03615326




Registration number
NCT03615326
Ethics application status
Date submitted
31/07/2018
Date registered
3/08/2018

Titles & IDs
Public title
Pembrolizumab/Placebo Plus Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-811/KEYNOTE-811)
Scientific title
A Phase III, Randomized, Double-blind Trial Comparing Trastuzumab Plus Chemotherapy and Pembrolizumab With Trastuzumab Plus Chemotherapy and Placebo as First-line Treatment in Participants With HER2 Positive Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (KEYNOTE 811)
Secondary ID [1] 0 0
MK-3475-811
Secondary ID [2] 0 0
3475-811
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastric Neoplasms 0 0
Gastroesophageal Junction Adenocarcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Oesophageal (gullet)
Cancer 0 0 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Pembrolizumab
Treatment: Other - Placebo
Treatment: Drugs - Cisplatin
Treatment: Drugs - 5-FU
Treatment: Drugs - Oxaliplatin
Treatment: Drugs - Capecitabine
Treatment: Drugs - S-1
Treatment: Other - Trastuzumab

Experimental: Pembrolizumab +Trastuzumab + Chemotherapy - Participants receive 200 mg pembrolizumab IV every 3 weeks (Q3W) plus trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance thereafter) IV Q3W in combination with FP or CAPOX chemotherapy (Global Cohort) or SOX chemotherapy (Japan cohort).

Active comparator: Placebo +Trastuzumab + Chemotherapy - Participants receive matched placebo to pembrolizumab IV Q3W plus trastuzumab (8mg/kg loading dose, 6mg/kg maintenance thereafter) IV Q3W in combination with FP or CAPOX chemotherapy (Global Cohort) or SOX chemotherapy (Japan cohort).


Treatment: Other: Pembrolizumab
200 mg on Day 1 of each 3-week cycle as an IV infusion.

Treatment: Other: Placebo
Solution for IV infusion on Day 1 of each 3-week cycle.

Treatment: Drugs: Cisplatin
80 mg/m\^2 on Day 1 of each 3-week cycle as an IV infusion, administered as part of FP chemotherapy regimen.

Treatment: Drugs: 5-FU
800 mg/m\^2/day continuous on Days 1-5 of each 3-week cycle (120 hours or per local standard), administered as part of FP chemotherapy regimen.

Treatment: Drugs: Oxaliplatin
130 mg/m\^2 on Day 1 of each 3-week cycle over 2 hours as an IV infusion, administered as part of CAPOX chemotherapy regimen and as part of SOX chemotherapy regimen.

Treatment: Drugs: Capecitabine
1000 mg/m\^2 as oral capsules BID on Days 1-14 of each 3-week cycle, administered as part of CAPOX chemotherapy regimen.

Treatment: Drugs: S-1
Combination product of tegafur, CDHP, and Oxo. Oral capsules BID on Days 1-14 of each 3-week cycle based on body surface area (BSA): \<1.25 m\^2 BSA =40 mg, 1.25 to \<1.5 m\^2 BSA=50 mg, =1.5 m\^2 BSA=60 mg. Administered as part of SOX chemotherapy regimen.

Treatment: Other: Trastuzumab
8 mg/kg loading dose and then 6 mg/kg maintenance dose administered IV on day 1 of each 3-week cycle.

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
Progression Free Survival (PFS) per RECIST 1.1 assessed by BICR
Timepoint [1] 0 0
Up to approximately 4 years
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 5 years
Secondary outcome [1] 0 0
Objective Response Rate (ORR) per RECIST 1.1 assessed by BICR
Timepoint [1] 0 0
Up to approximately 5 years
Secondary outcome [2] 0 0
Duration of Response (DOR) per RECIST 1.1 assessed by BICR
Timepoint [2] 0 0
Up to approximately 5 years
Secondary outcome [3] 0 0
Adverse Events (AE)
Timepoint [3] 0 0
Up to approximately 5 years
Secondary outcome [4] 0 0
Treatment Discontinuations Due to AEs
Timepoint [4] 0 0
Up to approximately 5 years

Eligibility
Key inclusion criteria
* Histologically or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic HER2 positive gastric or GEJ adenocarcinoma
* HER2-positive defined as either immunohistochemistry (IHC) 3+ or IHC 2+ in combination with in-situ hybridization positive (ISH+) or fluorescent in-situ hybridization (FISH), as assessed by central review on primary or metastatic tumor
* Has measurable disease as defined by RECIST 1.1 as determined by the site investigator
* Male participants must agree to use approved contraception
* Female participants who are not pregnant or breastfeeding, and who are either not a woman of childbearing potential (WOCBP), or are a WOCBP who agrees to use approved contraception
* Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 3 days prior to the first dose of trial treatment
* Has a life expectancy of greater than 6 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
* Has had previous therapy for locally advanced unresectable or metastatic gastric/GEJ cancer
* Has had major surgery, open biopsy or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of study treatment
* Has had radiotherapy within 14 days of randomization
* Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has an active autoimmune disease that has required systemic treatment in past 2 years
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
* Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
* Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis)
* Has an active infection requiring systemic therapy
* Has poorly controlled diarrhea
* Accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment. If the participant is receiving diuretic drugs for other reasons, it is acceptable
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
* Has peripheral neuropathy > Grade 1
* Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
* A WOCBP who has a positive urine pregnancy test within 24 hours prior to randomization or treatment allocation
* Has active or clinically significant cardiac disease
* Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
* Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
* Has severe hypersensitivity (=Grade 3) to pembrolizumab, trastuzumab, study chemotherapy agents and/or to any excipients, murine proteins, or platinum-containing products
* Has had an allogeneic tissue/solid organ transplant
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, Cluster of Differentiation 137 [CD137])

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 administering 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,VIC
Recruitment hospital [1] 0 0
Liverpool Hospital ( Site 2206) - Liverpool
Recruitment hospital [2] 0 0
Westmead Hospital ( Site 2200) - Westmead
Recruitment hospital [3] 0 0
Southern Medical Day Care Centre ( Site 2207) - Wollongong
Recruitment hospital [4] 0 0
Monash Health ( Site 2202) - Clayton
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
2500 - Wollongong
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Oklahoma
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
South Dakota
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Virginia
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
Brazil
State/province [17] 0 0
Bahia
Country [18] 0 0
Brazil
State/province [18] 0 0
Ceara
Country [19] 0 0
Brazil
State/province [19] 0 0
Parana
Country [20] 0 0
Brazil
State/province [20] 0 0
Rio Grande Do Sul
Country [21] 0 0
Brazil
State/province [21] 0 0
Santa Catarina
Country [22] 0 0
Brazil
State/province [22] 0 0
Rio de Janeiro
Country [23] 0 0
Brazil
State/province [23] 0 0
Sao Paulo
Country [24] 0 0
Chile
State/province [24] 0 0
Araucania
Country [25] 0 0
Chile
State/province [25] 0 0
Maule
Country [26] 0 0
Chile
State/province [26] 0 0
Region M. De Santiago
Country [27] 0 0
China
State/province [27] 0 0
Anhui
Country [28] 0 0
China
State/province [28] 0 0
Beijing
Country [29] 0 0
China
State/province [29] 0 0
Fujian
Country [30] 0 0
China
State/province [30] 0 0
Guangdong
Country [31] 0 0
China
State/province [31] 0 0
Heilongjiang
Country [32] 0 0
China
State/province [32] 0 0
Henan
Country [33] 0 0
China
State/province [33] 0 0
Hunan
Country [34] 0 0
China
State/province [34] 0 0
Jiangsu
Country [35] 0 0
China
State/province [35] 0 0
Jilin
Country [36] 0 0
China
State/province [36] 0 0
Shanghai
Country [37] 0 0
China
State/province [37] 0 0
Xinjiang
Country [38] 0 0
China
State/province [38] 0 0
Zhejiang
Country [39] 0 0
France
State/province [39] 0 0
Ain
Country [40] 0 0
France
State/province [40] 0 0
Bas-Rhin
Country [41] 0 0
France
State/province [41] 0 0
Doubs
Country [42] 0 0
France
State/province [42] 0 0
Finistere
Country [43] 0 0
France
State/province [43] 0 0
Nord
Country [44] 0 0
France
State/province [44] 0 0
Rhone
Country [45] 0 0
France
State/province [45] 0 0
Val-de-Marne
Country [46] 0 0
France
State/province [46] 0 0
Paris
Country [47] 0 0
Germany
State/province [47] 0 0
Baden-Wurttemberg
Country [48] 0 0
Germany
State/province [48] 0 0
Bayern
Country [49] 0 0
Germany
State/province [49] 0 0
Niedersachsen
Country [50] 0 0
Germany
State/province [50] 0 0
Sachsen
Country [51] 0 0
Germany
State/province [51] 0 0
Berlin
Country [52] 0 0
Germany
State/province [52] 0 0
Bremen
Country [53] 0 0
Germany
State/province [53] 0 0
Hamburg
Country [54] 0 0
Guatemala
State/province [54] 0 0
Guatemala
Country [55] 0 0
Guatemala
State/province [55] 0 0
Quetzaltenango
Country [56] 0 0
Ireland
State/province [56] 0 0
Dublin
Country [57] 0 0
Israel
State/province [57] 0 0
Beer Sheva
Country [58] 0 0
Israel
State/province [58] 0 0
Haifa
Country [59] 0 0
Israel
State/province [59] 0 0
Holon
Country [60] 0 0
Israel
State/province [60] 0 0
Jerusalem
Country [61] 0 0
Israel
State/province [61] 0 0
Kfar-Saba
Country [62] 0 0
Israel
State/province [62] 0 0
Petah Tikva
Country [63] 0 0
Israel
State/province [63] 0 0
Ramat Gan
Country [64] 0 0
Israel
State/province [64] 0 0
Tel Aviv
Country [65] 0 0
Italy
State/province [65] 0 0
Toscana
Country [66] 0 0
Italy
State/province [66] 0 0
Bergamo
Country [67] 0 0
Italy
State/province [67] 0 0
Catanzaro
Country [68] 0 0
Italy
State/province [68] 0 0
Milano
Country [69] 0 0
Italy
State/province [69] 0 0
Modena
Country [70] 0 0
Italy
State/province [70] 0 0
Napoli
Country [71] 0 0
Italy
State/province [71] 0 0
Padova
Country [72] 0 0
Italy
State/province [72] 0 0
Pescara
Country [73] 0 0
Japan
State/province [73] 0 0
Aichi
Country [74] 0 0
Japan
State/province [74] 0 0
Chiba
Country [75] 0 0
Japan
State/province [75] 0 0
Ehime
Country [76] 0 0
Japan
State/province [76] 0 0
Gunma
Country [77] 0 0
Japan
State/province [77] 0 0
Hyogo
Country [78] 0 0
Japan
State/province [78] 0 0
Ibaraki
Country [79] 0 0
Japan
State/province [79] 0 0
Kagawa
Country [80] 0 0
Japan
State/province [80] 0 0
Kanagawa
Country [81] 0 0
Japan
State/province [81] 0 0
Miyagi
Country [82] 0 0
Japan
State/province [82] 0 0
Osaka
Country [83] 0 0
Japan
State/province [83] 0 0
Saitama
Country [84] 0 0
Japan
State/province [84] 0 0
Shizuoka
Country [85] 0 0
Japan
State/province [85] 0 0
Tochigi
Country [86] 0 0
Japan
State/province [86] 0 0
Tokyo
Country [87] 0 0
Japan
State/province [87] 0 0
Fukuoka
Country [88] 0 0
Japan
State/province [88] 0 0
Gifu
Country [89] 0 0
Japan
State/province [89] 0 0
Hiroshima
Country [90] 0 0
Japan
State/province [90] 0 0
Kumamoto
Country [91] 0 0
Japan
State/province [91] 0 0
Niigata
Country [92] 0 0
Korea, Republic of
State/province [92] 0 0
Seoul
Country [93] 0 0
New Zealand
State/province [93] 0 0
Auckland
Country [94] 0 0
Poland
State/province [94] 0 0
Dolnoslaskie
Country [95] 0 0
Poland
State/province [95] 0 0
Lubelskie
Country [96] 0 0
Poland
State/province [96] 0 0
Mazowieckie
Country [97] 0 0
Poland
State/province [97] 0 0
Pomorskie
Country [98] 0 0
Poland
State/province [98] 0 0
Slaskie
Country [99] 0 0
Poland
State/province [99] 0 0
Wielkopolskie
Country [100] 0 0
Russian Federation
State/province [100] 0 0
Baskortostan, Respublika
Country [101] 0 0
Russian Federation
State/province [101] 0 0
Chelyabinskaya Oblast
Country [102] 0 0
Russian Federation
State/province [102] 0 0
Moskovskaya Oblast
Country [103] 0 0
Russian Federation
State/province [103] 0 0
Moskva
Country [104] 0 0
Russian Federation
State/province [104] 0 0
Samarskaya Oblast
Country [105] 0 0
Russian Federation
State/province [105] 0 0
Sankt-Peterburg
Country [106] 0 0
Spain
State/province [106] 0 0
Alicante
Country [107] 0 0
Spain
State/province [107] 0 0
Asturias
Country [108] 0 0
Spain
State/province [108] 0 0
Barcelona
Country [109] 0 0
Spain
State/province [109] 0 0
Cantabria
Country [110] 0 0
Spain
State/province [110] 0 0
Madrid
Country [111] 0 0
Turkey
State/province [111] 0 0
Adana
Country [112] 0 0
Turkey
State/province [112] 0 0
Ankara
Country [113] 0 0
Turkey
State/province [113] 0 0
Edirne
Country [114] 0 0
Turkey
State/province [114] 0 0
Erzurum
Country [115] 0 0
Turkey
State/province [115] 0 0
Istanbul
Country [116] 0 0
Turkey
State/province [116] 0 0
Izmir
Country [117] 0 0
Turkey
State/province [117] 0 0
Malatya
Country [118] 0 0
Turkey
State/province [118] 0 0
Sakarya
Country [119] 0 0
Ukraine
State/province [119] 0 0
Dnipropetrovska Oblast
Country [120] 0 0
Ukraine
State/province [120] 0 0
Ivano-Frankivska Oblast
Country [121] 0 0
Ukraine
State/province [121] 0 0
Kharkivska Oblast
Country [122] 0 0
Ukraine
State/province [122] 0 0
Kyivska Oblast
Country [123] 0 0
Ukraine
State/province [123] 0 0
Lvivska Oblast
Country [124] 0 0
Ukraine
State/province [124] 0 0
Odeska Oblast
Country [125] 0 0
Ukraine
State/province [125] 0 0
Zaporizka Oblast
Country [126] 0 0
Ukraine
State/province [126] 0 0
Kyiv
Country [127] 0 0
United Kingdom
State/province [127] 0 0
Derbyshire
Country [128] 0 0
United Kingdom
State/province [128] 0 0
Dundee City
Country [129] 0 0
United Kingdom
State/province [129] 0 0
East Riding Of Yorkshire
Country [130] 0 0
United Kingdom
State/province [130] 0 0
London, City Of
Country [131] 0 0
United Kingdom
State/province [131] 0 0
Surrey
Country [132] 0 0
United Kingdom
State/province [132] 0 0
London
Country [133] 0 0
United Kingdom
State/province [133] 0 0
Manchester
Country [134] 0 0
United Kingdom
State/province [134] 0 0
Northwood
Country [135] 0 0
United Kingdom
State/province [135] 0 0
Walsall

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?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.