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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03924856




Registration number
NCT03924856
Ethics application status
Date submitted
22/04/2019
Date registered
23/04/2019
Date last updated
2/11/2023

Titles & IDs
Public title
Perioperative Pembrolizumab (MK-3475) Plus Neoadjuvant Chemotherapy Versus Perioperative Placebo Plus Neoadjuvant Chemotherapy for Cisplatin-eligible Muscle-invasive Bladder Cancer (MIBC) (MK-3475-866/KEYNOTE-866)
Scientific title
A Phase 3, Randomized, Double-blind Study to Evaluate Perioperative Pembrolizumab (MK-3475) + Neoadjuvant Chemotherapy Versus Perioperative Placebo + Neoadjuvant Chemotherapy in Cisplatin-eligible Participants With Muscle-invasive Bladder Cancer (KEYNOTE-866)
Secondary ID [1] 0 0
MK-3475-866
Secondary ID [2] 0 0
3475-866
Universal Trial Number (UTN)
Trial acronym
KEYNOTE-866
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bladder Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bladder - transitional cell cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Cisplatin
Treatment: Surgery - Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])
Treatment: Drugs - Placebo

Experimental: Pembrolizumab + Gemcitabine + Cisplatin + Surgery - Participants received 4 preoperative cycles of pembrolizumab PLUS gemcitabine PLUS cisplatin, followed by surgery, followed by up to 13 cycles of postoperative pembrolizumab.

Placebo Comparator: Placebo + Gemcitabine + Cisplatin + Surgery - Participants received 4 preoperative cycles of placebo to pembrolizumab PLUS gemcitabine PLUS cisplatin, followed by surgery, followed by up to 13 cycles of postoperative placebo to pembrolizumab.


Treatment: Drugs: Pembrolizumab
Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle

Treatment: Drugs: Gemcitabine
Gemcitabine 1000 mg/m^2, IV infusion on Days 1 and 8 of each 21-day cycle

Treatment: Drugs: Cisplatin
Cisplatin 70 mg/m^2, IV infusion on Day 1 of each 21-day cycle

Treatment: Surgery: Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])
Surgical RC+PLND will be done in accordance with the American Urological Association (AUA)/American Society of Clinical Oncology (ASCO)/American Society for Radiation Oncology (ASTRO)/Society of Urologic Oncology (SUO) guidelines.

Treatment: Drugs: Placebo
Placebo to pembrolizumab by IV infusion, given on Day 1 of each 21-day cycle
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-Free Survival (EFS)
Timepoint [1] 0 0
Up to approximately 60 months
Secondary outcome [1] 0 0
Pathologic Complete Response (pCR) Rate
Timepoint [1] 0 0
Up to approximately 72 months
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 72 months
Secondary outcome [3] 0 0
Disease-Free Survival (DFS)
Timepoint [3] 0 0
From approximately 20 weeks up to approximately 72 months
Secondary outcome [4] 0 0
Pathologic Downstaging (pDS) Rate
Timepoint [4] 0 0
Up to approximately 72 months
Secondary outcome [5] 0 0
Number of Participants Who Experienced an Adverse Event (AE)
Timepoint [5] 0 0
Up to approximately 72 months
Secondary outcome [6] 0 0
Number of Participants Who Discontinued Study Treatment Due to an AE
Timepoint [6] 0 0
Up to approximately 12 months
Secondary outcome [7] 0 0
Number of Participants Who Experienced Perioperative Complications
Timepoint [7] 0 0
Up to approximately 12 months
Secondary outcome [8] 0 0
Change in Patient-Reported Outcomes from Baseline in Total Score of Functional Assessment of Cancer Therapy - General (FACT-G)
Timepoint [8] 0 0
Baseline, Up to approximately 72 months
Secondary outcome [9] 0 0
Change in Patient-Reported Outcomes from Baseline in Total Score of FACT-Bladder- (FACT-BI-Cys)
Timepoint [9] 0 0
Baseline, Up to approximately 72 months
Secondary outcome [10] 0 0
Change in Patient-Reported Outcomes from Baseline in FACT-BI-Cys-Trial Outcome Index (TOI)
Timepoint [10] 0 0
Baseline, Up to approximately 72 months
Secondary outcome [11] 0 0
Change in Patient-Reported Outcomes from Baseline in EuroQol Five-Dimensional Questionnaire (EQ-5D-5L) Visual Analog Score (VAS)
Timepoint [11] 0 0
Baseline, Up to approximately 72 months
Secondary outcome [12] 0 0
Time to Deterioration (TTD) in the Total Score of FACT-G
Timepoint [12] 0 0
Up to approximately 72 months
Secondary outcome [13] 0 0
TTD in EQ-5D-5L VAS
Timepoint [13] 0 0
Up to approximately 72 months

Eligibility
Key inclusion criteria
- Have a histologically confirmed diagnosis of urothelial carcinoma (UC) / muscle
invasive bladder cancer (MIBC) (T2-T4aN0M0 or T1-T4aN1M0) with predominant (=50%)
urothelial histology.

- Have clinically non-metastatic bladder cancer (N=1 M0) determined by imaging (computed
tomography (CT) or magnetic resonance imaging (MRI)) of the chest/abdomen/pelvis.

- Be deemed eligible for Radical Cystectomy (RC) + Pelvic Lymph Node Dissection (PLND).

- Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

- Have adequate organ function.

- Male and female participants are eligible to participate if they agree to the
contraception use as per study protocol.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Has a known additional malignancy that is progressing or has required active
anti-cancer treatment =3 years of study randomization with certain exceptions.

- Has received any prior systemic treatment for MIBC or non-invasive muscle bladder
cancer (NMIBC - prior treatment for NMIBC with intravesical BCG/chemotherapy is
permitted) or prior therapy with an anti- programmed cell death 1 (PD-1),
anti-programmed cell death ligand 1/ ligand 2 (PD-L1/L2), or anti-cytotoxic
T-lymphocyte-associated protein 4 (CTLA-4).

- Has =N2 disease or metastatic disease (M1) as identified by imaging.

- Is cisplatin-ineligible, as defined by meeting any one of the cisplatin ineligibility
criteria as per protocol.

- Has received prior systemic anticancer therapy including investigational agents within
3 years of randomization or any radiotherapy to the bladder.

- Has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC.

- Has received a live or live attenuated vaccine within 30 days before the first dose of
study intervention.

- Has a diagnosis of immunodeficiency or has a known history of human immunodeficiency
virus (HIV) infection, Hepatitis B infection or known active Hepatitis C infection.

- Has a known psychiatric or substance abuse disorder.

- 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 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
13/06/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/06/2025
Actual
Sample size
Target
Accrual to date
Final
907
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Mid North Coast Cancer Institute ( Site 1256) - Port Macquarie
Recruitment hospital [2] 0 0
Southside Cancer Care Centre ( Site 1252) - Sydney
Recruitment hospital [3] 0 0
Cairns Base Hospital ( Site 1257) - Cairns
Recruitment hospital [4] 0 0
Eastern Health ( Site 1255) - Box Hill
Recruitment hospital [5] 0 0
Peninsula Health Frankston Hospital ( Site 1258) - Frankston
Recruitment postcode(s) [1] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [2] 0 0
2228 - Sydney
Recruitment postcode(s) [3] 0 0
4870 - Cairns
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
3199 - Frankston
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
District of Columbia
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Florida
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Indiana
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Louisiana
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Maine
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Massachusetts
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Michigan
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Missouri
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New Jersey
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New Mexico
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New York
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Ohio
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Oklahoma
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Oregon
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West Virginia
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Bruxelles-Capitale, Region De
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Belgium
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Limburg
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Namur
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Oost-Vlaanderen
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Alberta
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Canada
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Nova Scotia
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Ontario
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Quebec
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Hovedstaden
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Syddanmark
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Aquitaine
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Auvergne
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France
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Calvados
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France
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Cotes-d Armor
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Hauts-de-Seine
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Languedoc-Roussillon
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France
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Maine-et-Loire
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Moselle
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France
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Puy-de-Dome
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Sarthe
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Vaucluse
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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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Sachsen-Anhalt
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Germany
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Sachsen
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Germany
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Schleswig-Holstein
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Germany
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Berlin
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Hungary
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Baranya
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Csongrad
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Jasz-Nagykun-Szolnok
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Budapest
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Debrecen
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Gyor
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Jerusalem
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Kfar Saba
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Petach Tikva
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Ramat Gan
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Tel Aviv
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Zerifin
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Italy
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Abruzzo
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Italy
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Emilia-Romagna
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Italy
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Catania
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Italy
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Milano
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Italy
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Napoli
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Pavia
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Roma
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Terni
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Aomori
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Chiba
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Ehime
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Hokkaido
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Nara
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Fukuoka
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Hiroshima
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Nagano
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Osaka
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Tokushima
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Japan
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Tokyo
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Korea, Republic of
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Kyonggi-do
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Korea, Republic of
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Seoul
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Mexico
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Nuevo Leon
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Mexico
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Aguascalientes
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Mexico
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Chihuahua
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Mexico
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Tlalpan
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Poland
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Dolnoslaskie
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Poland
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Kujawsko-pomorskie
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Poland
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Mazowieckie
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Poland
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Slaskie
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Russian Federation
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Baskortostan, Respublika
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Russian Federation
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Ivanovskaya Oblast
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Russian Federation
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Krasnoyarskiy Kray
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Russian Federation
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Kurskaya Oblast
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Russian Federation
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Moskva
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Russian Federation
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Murmanskaya Oblast
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Russian Federation
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Nizhegorodskaya Oblast
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Russian Federation
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Omskaya Oblast
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Russian Federation
State/province [108] 0 0
Sankt-Peterburg
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Russian Federation
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Saratovskaya Oblast
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Spain
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Extremadura
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Spain
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Gerona
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Spain
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Madrid, Comunidad De
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Spain
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Valenciana, Comunitat
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Spain
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Barcelona
Country [115] 0 0
Spain
State/province [115] 0 0
Madrid
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Spain
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Sevilla
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Sweden
State/province [117] 0 0
Jonkopings Lan
Country [118] 0 0
Sweden
State/province [118] 0 0
Uppsala Lan
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Sweden
State/province [119] 0 0
Vasterbottens Lan
Country [120] 0 0
Thailand
State/province [120] 0 0
Krung Thep Maha Nakhon
Country [121] 0 0
Thailand
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Chiang Mai
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Thailand
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Khon Kaen
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Turkey
State/province [123] 0 0
Ankara
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Turkey
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Istanbul
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Turkey
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Konya
Country [126] 0 0
Turkey
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Sakarya
Country [127] 0 0
Turkey
State/province [127] 0 0
Trabzon
Country [128] 0 0
Ukraine
State/province [128] 0 0
Cherkaska Oblast
Country [129] 0 0
Ukraine
State/province [129] 0 0
Dnipropetrovska Oblast
Country [130] 0 0
Ukraine
State/province [130] 0 0
Kharkivska Oblast
Country [131] 0 0
Ukraine
State/province [131] 0 0
Kyivska Oblast
Country [132] 0 0
Ukraine
State/province [132] 0 0
Lvivska Oblast
Country [133] 0 0
Ukraine
State/province [133] 0 0
Kyiv
Country [134] 0 0
United Kingdom
State/province [134] 0 0
Aberdeen City
Country [135] 0 0
United Kingdom
State/province [135] 0 0
Devon
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United Kingdom
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England
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United Kingdom
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Hertfordshire
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United Kingdom
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London, City Of
Country [139] 0 0
United Kingdom
State/province [139] 0 0
Norfolk
Country [140] 0 0
United Kingdom
State/province [140] 0 0
Truro

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

Ethics approval
Ethics application status

Summary
Brief summary
A global study to evaluate peri-operative pembrolizumab with chemotherapy versus placebo to
pembrolizumab plus chemotherapy in cisplatin eligible patients.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03924856
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03924856