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BRIEF TITLE: Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Participants With Muscle-invasive Bladder Cancer (MIBC) (KEYNOTE-992)

A Phase 3, Randomized, Double-blind, Placebo-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Participants With Muscle-invasive Bladder Cancer (MIBC) (KEYNOTE-992)


  • Org Study ID: 3475-992
  • Secondary ID: MK-3475-992,2019-004023-20,205383
  • NCT ID: NCT04241185
  • NCT Alias:
  • Sponsor: Merck Sharp & Dohme Corp. - Industry
  • Source: Merck Sharp & Dohme Corp.

Brief Summary

This study is designed to assess the antitumor efficacy and safety of pembrolizumab in combination with chemoradiotherapy (CRT) versus CRT alone in participants with muscle-invasive bladder cancer (MIBC). The primary hypothesis is that pembrolizumab + chemoradiotherapy is superior to placebo + chemoradiotherapy with respect to bladder intact event-free survival.

Overal Status Start Date Phase Study Type
Recruiting May 19, 2020 Phase 3 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Bladder Intact Event-Free Survival (BI-EFS)

Primary Outcome 1 - Time Frame: Up to approximately 71 months

Condition:

  • Urinary Bladder Neoplasms

Eligibility

Criteria:
Inclusion Criteria:

- Has a histologically confirmed diagnosis of MIBC with predominant urothelial histology

- Has clinically non-metastatic bladder cancer (N0M0)

- Has planned and is eligible to receive chemoradiotherapy (CRT) and one of the
protocol-specified radiosensitizing chemotherapy regimens

- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

- Demonstrates adequate organ function

- Male participants are eligible to participate if they agree to the following during
the intervention period and for at least 180 days after the last dose of study
intervention:

- Refrain from donating sperm

- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle
(abstinent on a long term and persistent basis) and agree to remain abstinent; or
must agree to use contraception unless confirmed to be azoospermic

- A female participant is eligible to participate if she is not pregnant or
breastfeeding, and at least one of the following conditions applies:

- Is not a woman of childbearing potential (WOCBP)

- Is a WOCBP and using a contraceptive method that is highly effective (with a
failure rate of <1% per year), with low user dependency or be abstinent from
heterosexual intercourse as their preferred and usual lifestyle (abstinent on a
long term and persistent basis), during the intervention period and for at least
180 days after the last dose of study intervention; and agrees not to donate eggs
(ova, oocytes) to others or freeze/store for her own use for the purpose of
reproduction during this period

Exclusion Criteria:

- Has the presence of diffuse carcinoma in situ (CIS) (multiple foci of CIS) throughout
the bladder

- Has the presence of urothelial carcinoma (UC) at any site outside of the urinary
bladder in the previous 2 years except for Ta stage/T1 stage/CIS of the upper tract if
the participant has undergone a complete nephroureterectomy

- Has a known additional malignancy that is progressing or has required active therapy
within the past 3 years, except basal cell carcinoma of the skin, squamous cell
carcinoma of the skin, superficial bladder cancer or other carcinoma in situ that has
undergone potentially curative therapy

- Has the presence of bilateral hydronephrosis

- Has limited bladder function with frequency of small amounts of urine (< 30 mL),
urinary incontinence, or requires self-catheterization or a permanent indwelling
catheter

- Has received prior pelvic/local radiation therapy or any antineoplastic treatment for
muscle-invasive bladder cancer (MIBC). Treatment for non-muscle invasive bladder
cancer (NMIBC) with intravesical instillation therapy that was completed ≥28 days
prior to randomization is allowed. Prior systemic treatment of NMIBC is not permitted.

- Received prior therapy with an anti-PD-1 (programmed cell death protein 1), anti-PD-L1
(programmed death-ligand 1), or anti-PD-L2 (programmed cell death 1 ligand 2), or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,
CTLA-4 [cytotoxic T-lymphocyte-associated protein 4], OX 40, or CD137 [cluster of
differentiation 137])

- Has received a live vaccine within 30 days prior to the first dose of study drug

- 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 intervention

- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or the selected
chemotherapy regimen, and/or any of their excipients

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug

- Has an active autoimmune disease that has required systemic treatment in the past 2
years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a form
of systemic treatment and is allowed

- 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 or known active Hepatitis C virus infection

- Has a known history of active tuberculosis (TB; Bacillus tuberculosis)

- 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 allogenic tissue/solid organ transplant
Show More

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Medical Director

Role: Study Director

Affiliation: Merck Sharp & Dohme Corp.

Overall Contact

Name: Toll Free Number

Phone: 1-888-577-8839

Email: Trialsites@merck.com

Locations

Facility Status Contact
Washington Cancer Institute at MedStar Washington Hospital Center ( Site 0041)
Washington, District of Columbia 20010
United States
Recruiting Study Coordinator
443-831-7296
Norton Cancer Institute ( Site 0044)
Louisville, Kentucky 40207
United States
Recruiting Study Coordinator
502-899-3366
Pikeville Medical Center ( Site 0009)
Pikeville, Kentucky 41501
United States
Recruiting Study Coordinator
606-218-2212
Washington University ( Site 0003)
Saint Louis, Missouri 63110
United States
Recruiting Study Coordinator
314-503-2992
New York Oncology Hematology P.C ( Site 0024)
Albany, New York 12206
United States
Recruiting Study Coordinator
518-489-3612
Saint Francis Cancer Center ( Site 0026)
Greenville, South Carolina 29607
United States
Recruiting Study Coordinator
864-603-6213
Carolina Urologic Research Center ( Site 0002)
Myrtle Beach, South Carolina 29572
United States
Recruiting Study Coordinator
843-449-1010 ext. 257
Northern Cancer Institute ( Site 0217)
St Leonards, New South Wales 2065
Australia
Recruiting Study Coordinator
61294631172
Fakultni nemocnice Olomouc ( Site 0559)
Olomouc, 779 00
Czechia
Recruiting Study Coordinator
+420588444295
2. LF UK a FN Motol ( Site 0555)
Praha 5, 150 06
Czechia
Recruiting Study Coordinator
+420266084516
Nemocnice Na Bulovce ( Site 0556)
Praha 8, 180 81
Czechia
Recruiting Study Coordinator
+420266084441
Herlev og Gentofte Hospital. ( Site 0401)
Herlev, Hovedstaden 2730
Denmark
Recruiting Study Coordinator
4538689572
Odense Universitetshospital ( Site 0403)
Odense, Syddanmark 5000
Denmark
Recruiting Study Coordinator
4538689572
North Estonia Medical Centre Foundation ( Site 0081)
Tallin, Harjumaa 13419
Estonia
Recruiting Study Coordinator
+3725134880
Tartu University Hospital ( Site 0079)
Tartu, Tartumaa 51014
Estonia
Recruiting Study Coordinator
+3727318815
Institut Sainte Catherine ( Site 0121)
Avignon, Provence-Alpes-Cote-d Azur 84918
France
Recruiting Study Coordinator
+33490276090
Centro Medico Integral de Cancerologia CEMIC ( Site 0144)
Salcaja, Quetzaltenango 09002
Guatemala
Recruiting Study Coordinator
+50259458053
Centro de Investigaciones Clinicas de Latinoamerica S.A. - CELAN ( Site 0146)
Guatemala, 01010
Guatemala
Recruiting Study Coordinator
+502 42142081
Oncomedica ( Site 0145)
Guatemala, 01010
Guatemala
Recruiting Study Coordinator
50222781268
Grupo Medico Angeles ( Site 0143)
Guatemala, 01015
Guatemala
Recruiting Study Coordinator
+50223857572
Medi-K Cayala ( Site 0142)
Guatemala, 01016
Guatemala
Recruiting Study Coordinator
+50223752222
Bacs-Kiskun Megyei Korhaz ( Site 0095)
Kecskemet, Bacs-Kiskun 6000
Hungary
Recruiting Study Coordinator
+3676516719
Chaim Sheba Medical Center ( Site 0087)
Ramat Gan, Tel Aviv 5265601
Israel
Recruiting Study Coordinator
+97235302542
Sourasky Medical Center ( Site 0089)
Tel Aviv, Tell Abib 6423906
Israel
Recruiting Study Coordinator
+97236973413
Rambam Medical Center ( Site 0088)
Afula, 1834111
Israel
Recruiting Study Coordinator
+97247773811
Hadassah Medical Center. Ein Kerem ( Site 0086)
Jerusalem, 9112001
Israel
Recruiting Study Coordinator
+97226776760
AOU Careggi ( Site 0191)
Firenze, 50134
Italy
Recruiting Study Coordinator
+390557947264
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0186)
Milano, 20133
Italy
Recruiting Study Coordinator
+390223902402
Azienda Ospedaliero - Universitaria Policlinico di Modena ( Site 0188)
Modena, 41124
Italy
Recruiting Study Coordinator
+390594222648
Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0192)
Napoli, 80131
Italy
Recruiting Study Coordinator
+390815903637
Hirosaki University Hospital ( Site 0602)
Hirosaki, Aomori 036-8563
Japan
Recruiting Study Coordinator
+81172335111
University of Tsukuba Hospital ( Site 0605)
Tsukuba, Ibaraki 305-8576
Japan
Recruiting Study Coordinator
+81298533900
Osaka Medical College Hospital ( Site 0604)
Takatsuki, Osaka 569-8686
Japan
Recruiting Study Coordinator
+81726831221
Nagasaki University Hospital ( Site 0600)
Nagasaki, 852-8501
Japan
Recruiting Study Coordinator
+81958197200
Medical Hospital, Tokyo Medical And Dental University ( Site 0601)
Tokyo, 113-8519
Japan
Recruiting Study Coordinator
+81338136111
National Cancer Center ( Site 0202)
Gyeonggi-do, Kyonggi-do 10408
Korea, Republic of
Recruiting Study Coordinator
+82319203679
Seoul National University Bundang Hospital ( Site 0204)
Seongnam-si, Kyonggi-do 13620
Korea, Republic of
Recruiting Study Coordinator
+82317877071
Chungnam National University Hospital ( Site 0203)
Daejeon, Taejon-Kwangyokshi 35015
Korea, Republic of
Recruiting Study Coordinator
+82422808369
Korea University Anam Hospital ( Site 0205)
Seoul, 02841
Korea, Republic of
Recruiting Study Coordinator
+8229206267
Severance Hospital Yonsei University Health System ( Site 0201)
Seoul, 03722
Korea, Republic of
Recruiting Study Coordinator
+82222288138
Asan Medical Center ( Site 0200)
Seoul, 05505
Korea, Republic of
Recruiting Study Coordinator
+82230105614
Pauls Stradins Clinical University Hospital ( Site 0073)
Riga, 1002
Latvia
Recruiting Study Coordinator
+37129262596
Hospital Universiti Sains Malaysia ( Site 0237)
Kubang Kerian, Kelantan 16150
Malaysia
Recruiting Study Coordinator
+6097676684
Hospital Pulau Pinang ( Site 0239)
Penang, Pulau Pinang 10990
Malaysia
Recruiting Study Coordinator
+6042225768
Hospital Kuala Lumpur ( Site 0238)
Kuala Lumpur, 50586
Malaysia
Recruiting Study Coordinator
+60326155810
University Malaya Medical Centre ( Site 0236)
Kuala Lumpur, 59100
Malaysia
Recruiting Study Coordinator
+60379492120
Netherlands Cancer Institute (NKI) ( Site 0183)
Amsterdam, Noord-Holland 1066 CX
Netherlands
Recruiting Study Coordinator
+31205122569
Erasmus MC ( Site 0182)
Rotterdam, Zuid-Holland 3015 GD
Netherlands
Recruiting Study Coordinator
+31107041505
Szpital Wojewodzki im. Mikolaja Kopernika ( Site 0152)
Koszalin, Zachodniopomorskie 75-581
Poland
Recruiting Study Coordinator
+48943488931
CHLO, EPE - Hospital de Sao Francisco Xavier ( Site 0302)
Lisboa, 1449-005
Portugal
Recruiting Study Coordinator
+351210431703
PAN American Center Oncologic ( Site 0280)
Rio Piedras, 00935
Puerto Rico
Recruiting Study Coordinator
7874073333
S.C. Radiotherapy Center Cluj S.R.L ( Site 0252)
Cluj-Napoca, Cluj 407280
Romania
Recruiting Study Coordinator
+40742206212
S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 0248)
Craiova, Dolj 200347
Romania
Recruiting Study Coordinator
+40722161545
Instituto Catalan de Oncologia - ICO ( Site 0103)
L Hospitalet De Llobregat, Barcelona 08908
Spain
Recruiting Study Coordinator
+34932607744
Hospital La Fe de Valencia ( Site 0105)
Valencia, Valenciana, Comunitat 46026
Spain
Recruiting Study Coordinator
+34961244188
Kaohsiung Chang Gung Memorial Hospital ( Site 0209)
Kaohsiung, 83301
Taiwan
Recruiting Study Coordinator
88677317123
National Cheng Kung University Hospital ( Site 0208)
Tainan, 704
Taiwan
Recruiting Study Coordinator
88662353535
National Taiwan University Hospital ( Site 0210)
Taipei, 10002
Taiwan
Recruiting Study Coordinator
+886966790736
Taipei Veterans General Hospital ( Site 0211)
Taipei, 112
Taiwan
Recruiting Study Coordinator
+886938591266
Chang Gung Medical Foundation-Linkou Branch ( Site 0212)
Taoyuan, 333
Taiwan
Recruiting Study Coordinator
+886 3-3281200 ext8825
Istanbul Uni. Cerrahpasa Tip Fakultesi ( Site 0501)
Istanbul, 34098
Turkey
Recruiting Study Coordinator
+905333682319
Medeniyet Universitesi Tip Fakultesi Tibbi Onkoloji Bolumu ( Site 0504)
Istanbul, 34732
Turkey
Recruiting Study Coordinator
+905063509061
Ege University Medical Faculty ( Site 0508)
Izmir, 35100
Turkey
Recruiting Study Coordinator
+905337360674
Karadeniz Teknik Universitesi Tip Fakultesi ( Site 0503)
Trabzon, 61080
Turkey
Recruiting Study Coordinator
+905052180361
Clinical oncology dispensary of Dnipro ( Site 0133)
Dnipro, Dnipropetrovska Oblast 49055
Ukraine
Recruiting Study Coordinator
+80687400930
Regional Oncology Center of Kharkiv ( Site 0134)
Kharkiv, Kharkivska Oblast 61000
Ukraine
Recruiting Study Coordinator
+380508266088
Grigoriev Institute for medical Radiology NAMS of Ukraine ( Site 0139)
Kharkiv, Kharkivska Oblast 61024
Ukraine
Recruiting Study Coordinator
+380669906870
Ukranian Center of TomoTherapy ( Site 0140)
Kropyvnytskiy, Kirovohradska Oblast 25011
Ukraine
Recruiting Study Coordinator
+380979428527
National Cancer Institute of the MoH of Ukraine ( Site 0136)
Kyiv, Kyivska Oblast 03022
Ukraine
Recruiting Study Coordinator
+380672365175
Kyiv City Clinical Oncology Center ( Site 0135)
Kyiv, Kyivska Oblast 03115
Ukraine
Recruiting Study Coordinator
+380667027558