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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03924856
Ethics application status
Date submitted
22/04/2019
Date registered
23/04/2019

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
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
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
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Louisiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Maine
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
New Jersey
Country [11] 0 0
United States of America
State/province [11] 0 0
New Mexico
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Oklahoma
Country [15] 0 0
United States of America
State/province [15] 0 0
Oregon
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Virginia
Country [19] 0 0
United States of America
State/province [19] 0 0
Washington
Country [20] 0 0
United States of America
State/province [20] 0 0
West Virginia
Country [21] 0 0
Belgium
State/province [21] 0 0
Bruxelles-Capitale, Region De
Country [22] 0 0
Belgium
State/province [22] 0 0
Limburg
Country [23] 0 0
Belgium
State/province [23] 0 0
Namur
Country [24] 0 0
Belgium
State/province [24] 0 0
Oost-Vlaanderen
Country [25] 0 0
Canada
State/province [25] 0 0
Alberta
Country [26] 0 0
Canada
State/province [26] 0 0
Nova Scotia
Country [27] 0 0
Canada
State/province [27] 0 0
Ontario
Country [28] 0 0
Canada
State/province [28] 0 0
Quebec
Country [29] 0 0
Denmark
State/province [29] 0 0
Hovedstaden
Country [30] 0 0
Denmark
State/province [30] 0 0
Syddanmark
Country [31] 0 0
France
State/province [31] 0 0
Aquitaine
Country [32] 0 0
France
State/province [32] 0 0
Auvergne
Country [33] 0 0
France
State/province [33] 0 0
Calvados
Country [34] 0 0
France
State/province [34] 0 0
Cotes-d Armor
Country [35] 0 0
France
State/province [35] 0 0
Hauts-de-Seine
Country [36] 0 0
France
State/province [36] 0 0
Languedoc-Roussillon
Country [37] 0 0
France
State/province [37] 0 0
Maine-et-Loire
Country [38] 0 0
France
State/province [38] 0 0
Moselle
Country [39] 0 0
France
State/province [39] 0 0
Puy-de-Dome
Country [40] 0 0
France
State/province [40] 0 0
Sarthe
Country [41] 0 0
France
State/province [41] 0 0
Seine-Maritime
Country [42] 0 0
France
State/province [42] 0 0
Vaucluse
Country [43] 0 0
Germany
State/province [43] 0 0
Baden-Wurttemberg
Country [44] 0 0
Germany
State/province [44] 0 0
Bayern
Country [45] 0 0
Germany
State/province [45] 0 0
Sachsen-Anhalt
Country [46] 0 0
Germany
State/province [46] 0 0
Sachsen
Country [47] 0 0
Germany
State/province [47] 0 0
Schleswig-Holstein
Country [48] 0 0
Germany
State/province [48] 0 0
Berlin
Country [49] 0 0
Hungary
State/province [49] 0 0
Baranya
Country [50] 0 0
Hungary
State/province [50] 0 0
Csongrad
Country [51] 0 0
Hungary
State/province [51] 0 0
Jasz-Nagykun-Szolnok
Country [52] 0 0
Hungary
State/province [52] 0 0
Budapest
Country [53] 0 0
Hungary
State/province [53] 0 0
Debrecen
Country [54] 0 0
Hungary
State/province [54] 0 0
Gyor
Country [55] 0 0
Hungary
State/province [55] 0 0
Kaposvar
Country [56] 0 0
Ireland
State/province [56] 0 0
Cork
Country [57] 0 0
Ireland
State/province [57] 0 0
Dublin
Country [58] 0 0
Ireland
State/province [58] 0 0
Waterford
Country [59] 0 0
Israel
State/province [59] 0 0
Afula
Country [60] 0 0
Israel
State/province [60] 0 0
Beer Sheva
Country [61] 0 0
Israel
State/province [61] 0 0
Haifa
Country [62] 0 0
Israel
State/province [62] 0 0
Jerusalem
Country [63] 0 0
Israel
State/province [63] 0 0
Kfar Saba
Country [64] 0 0
Israel
State/province [64] 0 0
Petach Tikva
Country [65] 0 0
Israel
State/province [65] 0 0
Ramat Gan
Country [66] 0 0
Israel
State/province [66] 0 0
Tel Aviv
Country [67] 0 0
Israel
State/province [67] 0 0
Zerifin
Country [68] 0 0
Italy
State/province [68] 0 0
Abruzzo
Country [69] 0 0
Italy
State/province [69] 0 0
Emilia-Romagna
Country [70] 0 0
Italy
State/province [70] 0 0
Catania
Country [71] 0 0
Italy
State/province [71] 0 0
Milano
Country [72] 0 0
Italy
State/province [72] 0 0
Napoli
Country [73] 0 0
Italy
State/province [73] 0 0
Pavia
Country [74] 0 0
Italy
State/province [74] 0 0
Roma
Country [75] 0 0
Italy
State/province [75] 0 0
Terni
Country [76] 0 0
Japan
State/province [76] 0 0
Aomori
Country [77] 0 0
Japan
State/province [77] 0 0
Chiba
Country [78] 0 0
Japan
State/province [78] 0 0
Ehime
Country [79] 0 0
Japan
State/province [79] 0 0
Hokkaido
Country [80] 0 0
Japan
State/province [80] 0 0
Ibaraki
Country [81] 0 0
Japan
State/province [81] 0 0
Kanagawa
Country [82] 0 0
Japan
State/province [82] 0 0
Nara
Country [83] 0 0
Japan
State/province [83] 0 0
Saitama
Country [84] 0 0
Japan
State/province [84] 0 0
Fukuoka
Country [85] 0 0
Japan
State/province [85] 0 0
Hiroshima
Country [86] 0 0
Japan
State/province [86] 0 0
Nagano
Country [87] 0 0
Japan
State/province [87] 0 0
Osaka
Country [88] 0 0
Japan
State/province [88] 0 0
Tokushima
Country [89] 0 0
Japan
State/province [89] 0 0
Tokyo
Country [90] 0 0
Korea, Republic of
State/province [90] 0 0
Kyonggi-do
Country [91] 0 0
Korea, Republic of
State/province [91] 0 0
Seoul
Country [92] 0 0
Mexico
State/province [92] 0 0
Nuevo Leon
Country [93] 0 0
Mexico
State/province [93] 0 0
Aguascalientes
Country [94] 0 0
Mexico
State/province [94] 0 0
Chihuahua
Country [95] 0 0
Mexico
State/province [95] 0 0
Tlalpan
Country [96] 0 0
Poland
State/province [96] 0 0
Dolnoslaskie
Country [97] 0 0
Poland
State/province [97] 0 0
Kujawsko-pomorskie
Country [98] 0 0
Poland
State/province [98] 0 0
Mazowieckie
Country [99] 0 0
Poland
State/province [99] 0 0
Slaskie
Country [100] 0 0
Russian Federation
State/province [100] 0 0
Baskortostan, Respublika
Country [101] 0 0
Russian Federation
State/province [101] 0 0
Ivanovskaya Oblast
Country [102] 0 0
Russian Federation
State/province [102] 0 0
Krasnoyarskiy Kray
Country [103] 0 0
Russian Federation
State/province [103] 0 0
Kurskaya Oblast
Country [104] 0 0
Russian Federation
State/province [104] 0 0
Moskva
Country [105] 0 0
Russian Federation
State/province [105] 0 0
Murmanskaya Oblast
Country [106] 0 0
Russian Federation
State/province [106] 0 0
Nizhegorodskaya Oblast
Country [107] 0 0
Russian Federation
State/province [107] 0 0
Omskaya Oblast
Country [108] 0 0
Russian Federation
State/province [108] 0 0
Sankt-Peterburg
Country [109] 0 0
Russian Federation
State/province [109] 0 0
Saratovskaya Oblast
Country [110] 0 0
Spain
State/province [110] 0 0
Extremadura
Country [111] 0 0
Spain
State/province [111] 0 0
Gerona
Country [112] 0 0
Spain
State/province [112] 0 0
Madrid, Comunidad De
Country [113] 0 0
Spain
State/province [113] 0 0
Valenciana, Comunitat
Country [114] 0 0
Spain
State/province [114] 0 0
Barcelona
Country [115] 0 0
Spain
State/province [115] 0 0
Madrid
Country [116] 0 0
Spain
State/province [116] 0 0
Sevilla
Country [117] 0 0
Sweden
State/province [117] 0 0
Jonkopings Lan
Country [118] 0 0
Sweden
State/province [118] 0 0
Uppsala Lan
Country [119] 0 0
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
State/province [121] 0 0
Chiang Mai
Country [122] 0 0
Thailand
State/province [122] 0 0
Khon Kaen
Country [123] 0 0
Turkey
State/province [123] 0 0
Ankara
Country [124] 0 0
Turkey
State/province [124] 0 0
Istanbul
Country [125] 0 0
Turkey
State/province [125] 0 0
Konya
Country [126] 0 0
Turkey
State/province [126] 0 0
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
Country [136] 0 0
United Kingdom
State/province [136] 0 0
England
Country [137] 0 0
United Kingdom
State/province [137] 0 0
Hertfordshire
Country [138] 0 0
United Kingdom
State/province [138] 0 0
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
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.