Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Muscle-invasive Bladder Cancer (MIBC) (MK-3475-992/KEYNOTE-992)
Urinary Bladder Neoplasms
About this trial
This is an interventional treatment trial for Urinary Bladder Neoplasms
Eligibility Criteria
Inclusion Criteria:
- Has a histologically confirmed initial diagnosis of muscle-invasive bladder cancer (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 90 days after the last dose of CRT treatment:
- 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 the time needed to eliminate each study intervention 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. The length of time required to continue contraception for each study intervention is as follows: MK-3475 - 120 days and CRT - 180 days
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 coinhibitory 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 before the first dose of study medication
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study medication
- Has known severe hypersensitivity (≥Grade 3) to the selected chemotherapy regimen, and/or any of their excipients and excipients of pembrolizumab
- 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 before the first dose of study medication
- 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
Sites / Locations
- Washington Cancer Institute at MedStar Washington Hospital Center ( Site 0041)Recruiting
- Bay Pines VA Medical Center ( Site 0055)
- AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlando ( Site 0004)
- Norton Cancer Institute ( Site 0044)
- Pikeville Medical Center ( Site 0009)Recruiting
- Baltimore VA Medical Center ( Site 0054)
- Washington University ( Site 0003)Recruiting
- Summit Medical Group Cancer Center ( Site 6008)Recruiting
- John Theurer Cancer Center at Hackensack University Medical Center ( Site 0005)Recruiting
- New York Oncology Hematology P.C ( Site 0024)Recruiting
- Winthrop University Hospital ( Site 0069)Recruiting
- New York University Perlmutter Cancer Center ( Site 0001)Recruiting
- Cleveland Clinic ( Site 0062)Recruiting
- MidLantic urology ( Site 0070)Recruiting
- Saint Francis Cancer Center ( Site 0026)
- Carolina Urologic Research Center ( Site 0002)Recruiting
- Urology San Antonio Research ( Site 6010)Recruiting
- Inova Schar Cancer Institute ( Site 6006)Recruiting
- West Virginia University - Charleston Area Medical Center ( Site 6003)Recruiting
- Froedtert and Medical College of Wisconsin ( Site 0022)Recruiting
- Liverpool Hospital ( Site 0220)
- GenesisCare North Shore ( Site 0217)Recruiting
- Monash Medical Centre ( Site 0216)
- Austin Health ( Site 0218)Recruiting
- Sir Charles Gairdner Hospital ( Site 0223)
- Oncocentro Valdivia ( Site 7055)Recruiting
- FALP ( Site 7056)Recruiting
- Bradfordhill-Clinical Area ( Site 7051)Recruiting
- ONCOCENTRO APYS-ACEREY ( Site 7054)Recruiting
- Centro de Investigación Oncológica del Norte ( Site 7052)Recruiting
- Fakultni nemocnice Olomouc ( Site 0559)Recruiting
- 2. LF UK a FN Motol ( Site 0555)Recruiting
- Nemocnice Na Bulovce ( Site 0556)
- Herlev og Gentofte Hospital. ( Site 0401)
- Odense Universitetshospital ( Site 0403)
- North Estonia Medical Centre Foundation ( Site 0081)Recruiting
- Tartu University Hospital ( Site 0079)Recruiting
- Institut Sainte Catherine ( Site 0121)Recruiting
- CHU Amiens Picardie Site Sud Amiens ( Site 0123)Recruiting
- Institut Curie ( Site 0112)
- A.P.H. Paris. Hopital Bichat Claude Bernard ( Site 0115)Recruiting
- Centro de Investigaciones Clinicas de Latinoamerica S.A. - CELAN ( Site 0146)Recruiting
- Oncomedica ( Site 0145)Recruiting
- Grupo Medico Angeles ( Site 0143)Recruiting
- Medi-K Cayala ( Site 0142)Recruiting
- Centro Medico Integral De Cancerología (CEMIC) ( Site 0144)Recruiting
- Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 0095)Recruiting
- BAZ Megyei Korhaz. Klinikai Onkologia es Sugarterapias Centrum ( Site 0092)Recruiting
- Petz Aladar Megyei Oktato Korhaz ( Site 0099)Recruiting
- Debreceni Egyetem Klinikai Kozpont ( Site 0097)Recruiting
- Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 0091)Recruiting
- Soroka Medical Center-Oncology ( Site 7031)Recruiting
- Rambam Health Care Campus-Oncology Division ( Site 0088)Recruiting
- Hadassah Medical Center. Ein Kerem ( Site 0086)Recruiting
- Rabin Medical Center ( Site 7032)Recruiting
- Chaim Sheba Medical Center ( Site 0087)Recruiting
- Sourasky Medical Center ( Site 0089)Recruiting
- Fondazione Policlinico Universitario Campus Bio-Medico-Radiation Oncology ( Site 7041)Recruiting
- Ospedale San Raffaele ( Site 0194)Recruiting
- IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 0193)Recruiting
- AOU Careggi ( Site 0191)Recruiting
- Ospedale Civile di Macerata ( Site 0190)Recruiting
- Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0186)Recruiting
- Azienda Ospedaliero - Universitaria Policlinico di Modena ( Site 0188)
- Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0192)Recruiting
- Hirosaki University Hospital ( Site 0602)Recruiting
- University of Tsukuba Hospital ( Site 0605)Recruiting
- Osaka Medical and Pharmaceutical University Hospital ( Site 0604)Recruiting
- Nagasaki University Hospital ( Site 0600)Recruiting
- Tokyo Medical and Dental University Hospital ( Site 0601)Recruiting
- Tokyo Metropolitan Komagome Hospital ( Site 0606)Recruiting
- National Cancer Center ( Site 0202)Recruiting
- Seoul National University Bundang Hospital ( Site 0204)Recruiting
- Asan Medical Center ( Site 0200)Recruiting
- Chungnam National University Hospital ( Site 0203)Recruiting
- Korea University Anam Hospital ( Site 0205)
- Severance Hospital Yonsei University Health System ( Site 0201)Recruiting
- Pauls Stradins Clinical University Hospital ( Site 0073)Recruiting
- Hospital Universiti Sains Malaysia ( Site 0237)Recruiting
- Hospital Pulau Pinang ( Site 0239)Recruiting
- Hospital Kuala Lumpur ( Site 0238)
- University Malaya Medical Centre ( Site 0236)Recruiting
- Netherlands Cancer Institute (NKI) ( Site 0183)Recruiting
- Erasmus MC ( Site 0182)Recruiting
- Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie ( Site 0153)Recruiting
- Mazowiecki Szpital Wojewódzki w Siedlcach ( Site 0154)Recruiting
- Szpital Wojewodzki im. Mikolaja Kopernika ( Site 0152)Recruiting
- Hospital Beatriz Angelo ( Site 0303)Recruiting
- Centro Hospitalar e Universitario de Coimbra ( Site 0306)Recruiting
- CHLO, EPE - Hospital de Sao Francisco Xavier ( Site 0302)Recruiting
- Centro Hospitalar Lisboa Norte EPE - Hospital de Santa Maria ( Site 0305)Recruiting
- Advance Urology and Laparoscopic Center ( Site 0281)Recruiting
- PAN American Center Oncologic ( Site 0280)Recruiting
- Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 0249)Recruiting
- S.C. Radiotherapy Center Cluj S.R.L ( Site 0252)Recruiting
- S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 0248)Recruiting
- Policlinica Oncomed SRL ( Site 0254)Recruiting
- S.C.Focus Lab Plus S.R.L ( Site 0253)Recruiting
- Institutul Oncologic-Oncologie Medicala ( Site 0256)Recruiting
- Institutul Regional de Oncologie Iasi ( Site 0255)
- Instituto Catalan de Oncologia - ICO ( Site 0103)Recruiting
- Hospital La Fe de Valencia ( Site 0105)Recruiting
- HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO-Medical Oncology ( Site 0106)Recruiting
- Chi Mei Medical Center ( Site 0215)Recruiting
- Kaohsiung Chang Gung Memorial Hospital ( Site 0209)Recruiting
- Taichung Veterans General Hospital ( Site 0213)Recruiting
- National Cheng Kung University Hospital ( Site 0208)
- National Taiwan University Hospital ( Site 0210)Recruiting
- Taipei Veterans General Hospital ( Site 0211)Recruiting
- Chang Gung Medical Foundation.Linkou Branch ( Site 0212)Recruiting
- University of Health Sciences,Gulhane School of Medicine-Oncology ( Site 0509)Recruiting
- Ankara Universitesi Tip Fakultesi. ( Site 0502)Recruiting
- Istanbul Uni. Cerrahpasa Tip Fakultesi ( Site 0501)Recruiting
- T.C. Saglik Bakanligi Turkiye Kamu Hastaneleri Kurumu - Baki-Istanbul Bakirkoy Sadi Konuk Training (Recruiting
- Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 0504)Recruiting
- Ege University Medical Faculty ( Site 0508)Recruiting
- Karadeniz Teknik Universitesi Tip Fakultesi ( Site 0503)Recruiting
- Clinical oncology dispensary of Dnipro ( Site 0133)
- Grigoriev Institute for medical Radiology NAMS of Ukraine ( Site 0139)
- CNPE "Regional Center of Oncology" ( Site 0134)
- Ukranian Center of TomoTherapy ( Site 0140)
- National Cancer Institute of the MoH of Ukraine ( Site 0136)
- Kyiv City Clinical Oncology Center ( Site 0135)
- Betsi Cadwaladr University Health Board ( Site 0447)
- South Devon Healthcare Foundation Trust. Torbay Hospital ( Site 0444)Recruiting
- University College London Hospitals NHS Foundation Trust ( Site 0445)Recruiting
- The Royal Marsden NHS Foundation Trust. ( Site 0442)Recruiting
- Nottingham University Hospital NHS Trust ( Site 0250)
- Darlington Memorial Hospital NHS Trust ( Site 0446)Recruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Pembrolizumab + Chemotherapy + Radiotherapy
Placebo + Chemotherapy + Radiotherapy
Participants receive pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.
Participants receive placebo to pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.