AzTrials
AzTrials

Urinary Bladder NeoplasmsPhase 3NCT04241185

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)

A Phase 3 study testing Pembrolizumab, Conventional Radiotherapy (Bladder only) and Conventional Radiotherapy (Bladder and pelvic nodes) in people with Urinary Bladder Neoplasms, run by Merck Sharp & Dohme LLC at 134 sites in 25 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

Researchers are looking for new ways to treat muscle-invasive bladder cancer (MIBC). MIBC is a type of cancer that has not spread from the muscles in the bladder to other parts of the body. MIBC is treated by having surgery to remove the bladder (cystectomy). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Urinary Bladder Neoplasms
What is being tested?
Pembrolizumab, Conventional Radiotherapy (Bladder only) and Conventional Radiotherapy (Bladder and pelvic nodes)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
520 participants
Where
134 sitesin 25 countries
Study dates
19 May 2020to 1 Nov 2031
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Has a histologically confirmed initial diagnosis of muscle-invasive bladder cancer (MIBC) with predominant urothelial histology
  • Has clinically nonmetastatic 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:
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  • 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

Who cannot join

  • 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 for any reason 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.
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  • 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

Trial locations and contacts

134 sites in 25 countries.

134 sites in 25 countries

United States24 sites

  • New York Oncology Hematology P.C ( Site 0024)

    Albany, New York, 12206

  • MidLantic urology ( Site 0070)

    Bala-Cynwyd, Pennsylvania, 19004

  • Baltimore VA Medical Center ( Site 0054)

    Baltimore, Maryland, 21201

  • Bay Pines VA Medical Center ( Site 0055)

    Bay Pines, Florida, 33744

  • Roswell Park Cancer Institute ( Site 6009)

    Buffalo, New York, 14263

  • West Virginia University - Charleston Area Medical Center ( Site 6003)

    Charleston, West Virginia, 25304

  • Fairview Hospital-Moll Cancer Center ( Site 6013)

    Cleveland, Ohio, 44111

  • Cleveland Clinic Main ( Site 0062)

    Cleveland, Ohio, 44195

  • Inova Schar Cancer Institute ( Site 6006)

    Fairfax, Virginia, 22031

  • Summit Medical Group Cancer Center ( Site 6008)

    Florham Park, New Jersey, 07932

  • Saint Francis Cancer Center ( Site 0026)

    Greenville, South Carolina, 29607

  • John Theurer Cancer Center at Hackensack University Medical Center ( Site 0005)

    Hackensack, New Jersey, 07601

  • Norton Cancer Institute ( Site 0044)

    Louisville, Kentucky, 40207

  • Cleveland Clinic - Hillcrest Hospital-Hillcrest Hospital Cancer Center ( Site 6012)

    Mayfield Heights, Ohio, 44124

  • Froedtert and Medical College of Wisconsin ( Site 0022)

    Milwaukee, Wisconsin, 53226

  • Winthrop University Hospital ( Site 0069)

    Mineola, New York, 11501

  • Carolina Urologic Research Center ( Site 0002)

    Myrtle Beach, South Carolina, 29572

  • New York University Perlmutter Cancer Center ( Site 0001)

    New York, New York, 10016

  • AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlandoc ( Site 0004)

    Orlando, Florida, 32804

  • Pikeville Medical Center ( Site 0009)

    Pikeville, Kentucky, 41501

  • Urology San Antonio Research ( Site 6010)

    San Antonio, Texas, 78229

  • Washington University ( Site 0003)

    St Louis, Missouri, 63110

  • Westchester Medical Center ( Site 6014)

    Valhalla, New York, 10595

  • Washington Cancer Institute at MedStar Washington Hospital Center ( Site 0041)

    Washington D.C., District of Columbia, 20010

Other trials in United States

Italy8 sites

  • IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 0193)

    Bari, Apulia, 70124

  • AOU Careggi ( Site 0191)

    Florence, 50134

  • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0186)

    Milan, Lombardy, 20133

  • Ospedale San Raffaele. ( Site 0194)

    Milan, 20132

  • Azienda Ospedaliero - Universitaria Policlinico di Modena ( Site 0188)

    Modena, 41124

  • Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0192)

    Naples, 80131

  • Ospedale Civile di Macerata ( Site 0190)

    Province of Macerata, 62100

  • Fondazione Policlinico Universitario Campus Bio-Medico-Radiation Oncology ( Site 7041)

    Rome, Lazio, 00128

Other trials in Italy

Romania7 sites

  • MEMORIAL HEALTHCARE INTERNATIONAL S.R.L. ( Site 0253)

    Bucharest, 013812

  • Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 0249)

    Cluj-Napoca, Cluj, 400015

  • S.C. Radiotherapy Center Cluj S.R.L ( Site 0252)

    Cluj-Napoca, Cluj, 407280

  • Institutul Oncologic-Oncologie Medicala ( Site 0256)

    Cluj-Napoca, 400015

  • S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 0248)

    Craiova, Dolj, 200542

  • Institutul Regional de Oncologie Iasi ( Site 0255)

    Iași, 700483

  • Policlinica Oncomed SRL ( Site 0254)

    Timișoara, Timiș County, 300239

Other trials in Romania

Taiwan7 sites

  • Kaohsiung Chang Gung Memorial Hospital ( Site 0209)

    Kaohsiung City, 83301

  • Taichung Veterans General Hospital ( Site 0213)

    Taichung, 407

  • Chi Mei Medical Center ( Site 0215)

    Tainan, Tainan, 71004

  • National Cheng Kung University Hospital ( Site 0208)

    Tainan, 704

  • National Taiwan University Hospital ( Site 0210)

    Taipei, 10002

  • Taipei Veterans General Hospital ( Site 0211)

    Taipei, 11217

  • Chang Gung Medical Foundation.Linkou Branch ( Site 0212)

    Taoyuan, 333

Other trials in Taiwan

Turkey (Türkiye)7 sites

  • University of Health Sciences,Gulhane School of Medicine-Oncology ( Site 0509)

    Ankara, 06010

  • Ankara Universitesi Tip Fakultesi. ( Site 0502)

    Ankara, 06100

  • Istanbul Uni. Cerrahpasa Tip Fakultesi ( Site 0501)

    Istanbul, 34098

  • T.C. Saglik Bakanligi Turkiye Kamu Hastaneleri Kurumu - Baki-Istanbul Bakirkoy Sadi Konuk Training ( Site 0510)

    Istanbul, 34147

  • Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 0504)

    Istanbul, 34722

  • Ege University Medical Faculty ( Site 0508)

    Izmir, 35100

  • Karadeniz Teknik Universitesi Tip Fakultesi ( Site 0503)

    Trabzon, 61080

Other trials in Turkey (Türkiye)

United Kingdom7 sites

  • Darlington Memorial Hospital NHS Trust ( Site 0446)

    Darlington, DL3 6HX

  • University College London Hospitals NHS Foundation Trust ( Site 0445)

    London, London, City of, NW1 2PG

  • The Royal Marsden NHS Foundation Trust. ( Site 0442)

    London, London, City of, SW3 6JJ

  • Nottingham University Hospital NHS Trust ( Site 0250)

    Nottingham, Nottinghamshire, NG5 1PB

  • Royal Preston Hospital ( Site 0449)

    Preston, Lancashire, PR2 9HT

  • Betsi Cadwaladr University Health Board ( Site 0447)

    Rhyl, Denbighshire, LL18 5UJ

  • South Devon Healthcare Foundation Trust. Torbay Hospital ( Site 0444)

    Torquay, Devon, TQ2 7AA

Other trials in United Kingdom

Israel6 sites

  • Soroka Medical Center-Oncology ( Site 7031)

    Beersheba, 8400000

  • Rambam Health Care Campus-Oncology Division ( Site 0088)

    Haifa, 3109601

  • Hadassah Medical Center. Ein Kerem ( Site 0086)

    Jerusalem, 9112001

  • Rabin Medical Center ( Site 7032)

    Petah Tikva, 4941492

  • Chaim Sheba Medical Center ( Site 0087)

    Ramat Gan, 5262000

  • Sourasky Medical Center ( Site 0089)

    Tel Aviv, 6423906

Other trials in Israel

Japan6 sites

  • Hirosaki University Hospital ( Site 0602)

    Hirosaki, Aomori, 036-8563

  • Nagasaki University Hospital ( Site 0600)

    Nagasaki, 852-8501

  • Osaka Medical and Pharmaceutical University Hospital ( Site 0604)

    Takatsuki, Osaka, 569-8686

  • Institute of Science Tokyo Hospital ( Site 0601)

    Tokyo, 113-8519

  • Tokyo Metropolitan Komagome Hospital ( Site 0606)

    Tokyo, 113-8677

  • University of Tsukuba Hospital ( Site 0605)

    Tsukuba, Ibaraki, 305-8576

Other trials in Japan

South Korea6 sites

  • Chungnam National University Hospital ( Site 0203)

    Daejeon, Taejon-Kwangyokshi, 35015

  • National Cancer Center ( Site 0202)

    Gyeonggi-do, Kyonggi-do, 10408

  • Seoul National University Bundang Hospital ( Site 0204)

    Seongnam-si, Kyonggi-do, 13620

  • Korea University Anam Hospital ( Site 0205)

    Seoul, 02841

  • Severance Hospital Yonsei University Health System ( Site 0201)

    Seoul, 03722

  • Asan Medical Center ( Site 0200)

    Seoul, 05505

Other trials in South Korea

Ukraine6 sites

  • Clinical oncology dispensary of Dnipro ( Site 0133)

    Dnipro, Dnipropetrovsk Oblast, 49055

  • Grigoriev Institute for medical Radiology NAMS of Ukraine ( Site 0139)

    Kharkiv, Kharkiv Oblast, 61024

  • MNPE Regional Center of Oncology ( Site 0134)

    Kharkiv, Kharkiv Oblast, 61070

  • Ukranian Center of TomoTherapy ( Site 0140)

    Kropyvnytskiy, Kirovohrad Oblast, 25011

  • SNPE National Cancer Institute ( Site 0136)

    Kyiv, 03022

  • Kyiv City Clinical Oncology Center ( Site 0135)

    Kyiv, 03115

Other trials in Ukraine

Australia5 sites

  • Monash Medical Centre ( Site 0216)

    Clayton, Victoria, 3168

  • Austin Health ( Site 0218)

    Heidelberg, Victoria, 3084

  • Liverpool Hospital ( Site 0220)

    Liverpool, New South Wales, 2170

  • Sir Charles Gairdner Hospital ( Site 0223)

    Nedlands, Western Australia, 6009

  • GenesisCare North Shore ( Site 0217)

    St Leonards, New South Wales, 2065

Other trials in Australia

Chile5 sites

  • Bradford Hill Norte ( Site 7052)

    Antofagasta, 1240000

  • FALP ( Site 7056)

    Santiago, Region M. de Santiago, 7500921

  • Bradfordhill-Clinical Area ( Site 7051)

    Santiago, Region M. de Santiago, 8420383

  • Oncocentro Valdivia ( Site 7055)

    Valdivia, Los Ríos Region, 5112129

  • ONCOCENTRO APYS-ACEREY ( Site 7054)

    Viña del Mar, Valparaiso, 2520598

Other trials in Chile

Guatemala5 sites

  • MEDI-K ( Site 0142)

    Guatemala City, 01009

  • Centro de Investigaciones Clinicas de Latinoamerica S.A. - CELAN ( Site 0146)

    Guatemala City, 01010

  • Oncomedica ( Site 0145)

    Guatemala City, 01010

  • Grupo Medico Angeles ( Site 0143)

    Guatemala City, 01015

  • Centro Medico Integral De Cancerología (CEMIC) ( Site 0144)

    Quetzaltenango, 09002

Other trials in Guatemala

Hungary5 sites

  • Debreceni Egyetem Klinikai Kozpont ( Site 0097)

    Debrecen, Hajdú-Bihar, 4032

  • Petz Aladar Megyei Oktato Korhaz ( Site 0099)

    Győr, Győr-Moson-Sopron, 9024

  • Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 0091)

    Kaposvár, 7400

  • Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 0095)

    Kecskemét, Bács-Kiskun county, 6000

  • BAZ Megyei Korhaz. Klinikai Onkologia es Sugarterapias Centrum ( Site 0092)

    Miskolc, Borsod-Abauj Zemplen county, 3526

Other trials in Hungary

France4 sites

  • CHU Amiens Picardie Site Sud Amiens ( Site 0123)

    Amiens, Somme, 80000

  • Institut Sainte Catherine ( Site 0121)

    Avignon, Provence-Alpes-Côte d'Azur Region, 84918

  • Institut Curie ( Site 0112)

    Paris, 75005

  • A.P.H. Paris. Hopital Bichat Claude Bernard ( Site 0115)

    Paris, 75018

Other trials in France

Malaysia4 sites

  • Hospital Pulau Pinang ( Site 0239)

    George Town, Pulau Pinang, 10990

  • Hospital Kuala Lumpur ( Site 0238)

    Kuala Lumpur, 50586

  • University Malaya Medical Centre ( Site 0236)

    Kuala Lumpur, 59100

  • Hospital Universiti Sains Malaysia ( Site 0237)

    Kubang Kerian, Kelantan, 16150

Other trials in Malaysia

Portugal4 sites

  • Centro Hospitalar e Universitario de Coimbra ( Site 0306)

    Coimbra, 3000-075

  • Unidade Local de Saude Lisboa Ocidental - Hospital de São Francisco Xavier ( Site 0302)

    Lisbon, 1449-005

  • Unidade Local de Saude de Santa Maria - Hospital de Santa Maria ( Site 0305)

    Lisbon, 1649-035

  • Unidade Local de Saude Loures-Odivelas - Hospital Beatriz Angelo ( Site 0303)

    Loures, Lisbon District, 2674-514

Other trials in Portugal

Czechia3 sites

  • Fakultni nemocnice Olomouc ( Site 0559)

    Olomouc, 77900

  • 2. LF UK a FN Motol ( Site 0555)

    Prague, 150 06

  • Nemocnice Na Bulovce ( Site 0556)

    Prague, 180 81

Other trials in Czechia

Poland3 sites

  • Szpital Wojewodzki im.M.Kopernika. ( Site 0152)

    Koszalin, West Pomeranian Voivodeship, 75-581

  • Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie ( Site 0153)

    Krakow, Lesser Poland Voivodeship, 31-826

  • Mazowiecki Szpital Wojewódzki w Siedlcach ( Site 0154)

    Siedlce, Masovian Voivodeship, 08-110

Other trials in Poland

Spain3 sites

  • Instituto Catalan de Oncologia - ICO ( Site 0103)

    L'Hospitalet de Llobregat, Barcelona, 08908

  • HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO-Medical Oncology ( Site 0106)

    Seville, 41013

  • Hospital La Fe de Valencia ( Site 0105)

    Valencia, Valenciana, Comunitat, 46026

Other trials in Spain

Denmark2 sites

  • Herlev og Gentofte Hospital. ( Site 0401)

    Herlev, Capital Region, 2730

  • Odense Universitetshospital ( Site 0403)

    Odense, Region Syddanmark, 5000

Other trials in Denmark

Estonia2 sites

  • North Estonia Medical Centre Foundation ( Site 0081)

    Tallinn, Harju, 13419

  • Tartu University Hospital ( Site 0079)

    Tartu, Tartu, 51014

Other trials in Estonia

Netherlands2 sites

  • Netherlands Cancer Institute (NKI) ( Site 0183)

    Amsterdam, North Holland, 1066 CX

  • Erasmus MC ( Site 0182)

    Rotterdam, South Holland, 3015 GD

Other trials in Netherlands

Puerto Rico2 sites

  • Advance Urology and Laparoscopic Center ( Site 0281)

    Ponce, 00716

  • PAN American Center Oncologic ( Site 0280)

    San Juan, Rio Piedras, 00935

Other trials in Puerto Rico

Latvia1 site

  • Pauls Stradins Clinical University Hospital ( Site 0073)

    Riga, LV-1002

Other trials in Latvia

About this study

Official title: 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)

Researchers are looking for new ways to treat muscle-invasive bladder cancer (MIBC). MIBC is a type of cancer that has not spread from the muscles in the bladder to other parts of the body.

MIBC is treated by having surgery to remove the bladder (cystectomy). Not all people choose to have surgery and want to keep their bladder using other treatments.

Read more

Chemoradiotherapy (CRT)- is a type of non-surgical treatment for MIBC which combines Chemotherapy (a treatment with medicine to destroy cancer cells or stop them growing) and Radiation therapy (a treatment that uses beams of intense energy [like X-rays] to shrink or get rid of tumors).

Pembrolizumab is an immunotherapy, which is a treatment that helps the immune system fight cancer.

A placebo looks like the study medicine but has no study medicine in it. Using a placebo helps researchers better understand if the study medicine works.

The goal of this study is to learn: 1. If a study medicine pembrolizumab given with Chemoradiotherapy (CRT) can help people live longer without their cancer growing, spreading, or coming back compared to placebo given with CRT. 2. About the safety and how well people tolerate CRT alone or in combination with pembrolizumab.

Being tested
Pembrolizumab, Conventional Radiotherapy (Bladder only), Conventional Radiotherapy (Bladder and pelvic nodes), Hypofractionated Radiotherapy (Bladder only), Cisplatin
Medical subject headings
Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Also called MK-3475, KEYTRUDA®

    400 mg of IV (intravenous) pembrolizumab once every 6 weeks.

  • Conventional Radiotherapy (Bladder only)Radiation

    64 Gy of radiation administered to participant's bladder only. Thirty-two fractions will be administered over 6.5 weeks.

  • Conventional Radiotherapy (Bladder and pelvic nodes)Radiation

    64 Gy of radiation administered to participant's bladder and pelvic nodes. Thirty-two fractions will be administered over 6.5 weeks.

  • Hypofractionated Radiotherapy (Bladder only)Radiation

    55 Gy of radiation administered to participant's bladder only. Twenty fractions will be administered over 4 weeks.

  • CisplatinDrug

    35 mg of cisplatin per cubic meter of body volume, administered once weekly via IV infusion.

  • Fluorouracil (5-FU)Drug

    5-FU administered via IV infusion at a dose of 500 mg per cubic meter of body volume on Days 1-5 and 22-26.

  • Mitomycin C (MMC)Drug

    MMC administered via IV infusion at a dose of 12 mg per cubic meter of body volume on Day 1.

  • GemcitabineDrug

    Gemcitabine administered via IV infusion at a dose of 27 mg per cubic meter of body volume twice weekly.

  • Placebo to PembrolizumabDrug

    Placebo to intravenous (IV) pembrolizumab administered once every 6 weeks.

Study groups in NCT04241185
Study groupRoleWhat they receive
Pembrolizumab + Chemotherapy + RadiotherapyExperimentalParticipants receive pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.
Receives: Drug: Pembrolizumab; Radiation: Conventional Radiotherapy (Bladder only); Radiation: Conventional Radiotherapy (Bladder and pelvic nodes); Radiation: Hypofractionated Radiotherapy (Bladder only); Drug: Cisplatin; Drug: Fluorouracil (5-FU); Drug: Mitomycin C (MMC); Drug: Gemcitabine
Placebo + Chemotherapy + RadiotherapyPlacebo comparatorParticipants receive placebo to pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.
Receives: Radiation: Conventional Radiotherapy (Bladder only); Radiation: Conventional Radiotherapy (Bladder and pelvic nodes); Radiation: Hypofractionated Radiotherapy (Bladder only); Drug: Cisplatin; Drug: Fluorouracil (5-FU); Drug: Mitomycin C (MMC); Drug: Gemcitabine; Drug: Placebo to Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Bladder Intact Event-Free Survival (BI-EFS)

    BI-EFS is defined as the time from randomization to any of the following events: residual/recurrent MIBC post-chemoradiotherapy (CRT), nodal or distant metastases as assessed by computerized tomography (CT) and CT urography (CTU) or magnetic resonance urography (MRU) per blinded independent central review (BICR) and/or biopsy results assessed by central pathology review, radical cystectomy, or death due to any cause. If biopsy is not feasible due to participant safety, the imaging alone will be sufficient. The BI-EFS for all participants will be presented.

    Measured: Up to approximately 76 months

Secondary outcomes (10)

  1. Overall Survival (OS)

    Time from randomization to death due to any cause.

    Measured: Up to approximately 7 years

  2. Metastasis-Free Survival (MFS)

    MFS is defined as the time from randomization to the first documented occurrence of nodal or distant metastases as assessed by CT and CTU or MRU per BICR and/or biopsy results assessed by central pathology review If biopsy is not feasible due to participant safety, the imaging alone will be sufficient.

    Measured: Up to approximately 7 years

  3. Time to Occurrence of Non-Muscle-Invasive Bladder Cancer (NMIBC)

    Time to occurrence of low-grade disease, defined as the time from randomization until the development of NMIBC, will be presented.

    Measured: Up to approximately 7 years

  4. Number of Participants Who Experienced an Adverse Event (AE)

    An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be presented.

    Measured: Up to approximately 7 years

  5. Number of Participants Who Discontinued Study Intervention Due to an AE

    An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be presented.

    Measured: Up to approximately 1 year

  6. Change from Baseline in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)

    The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall outcome. The change from baseline in Global Health Status/Quality of Life (EORTC QLQ-C30 Items 29 and 30) combined score will be presented.

    Measured: Baseline and up to approximately 2 years

  7. Change from Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30

    EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a better quality of life. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) combined score will be presented.

    Measured: Baseline and up to approximately 2 years

  8. Change from Baseline in Urinary, Bowel, and Sexual Domains of the Bladder Cancer Index (BCI)

    The BCI is a validated, condition-specific health questionnaire assessing quality of life among participants with bladder cancer. The BCI contains 36 items which assess 3 domains (urinary, bowel, and sexual) with function and bother subdomains. Scores range from 0 to 100 with higher scores corresponding to better functioning and health-related quality of life. The change from baseline in the combined scores of the urinary, bowel, and sexual domains of the BCI will be presented.

    Measured: Baseline and up to approximately 2 years

  9. Change from Baseline in the Visual Analog Score (VAS) of the European Quality of Life (EuroQoL)-5 Dimensions, 5-level Questionnaire (EQ-5D-5L)

    The EQ-5D-5L VAS records the respondent's self-rated health on a 10 cm vertical, visual analogue scale. It is rated by the respondent on a scale 0 to 100, with 0 being "the worst health you can imagine" and 100 being "the best health you can imagine". The change from baseline in EQ-5D-5L VAS will be presented.

    Measured: Baseline and up to approximately 2 years

  10. Time to Cystectomy

    Time to cystectomy is defined as time from a participant's randomization to date of cystectomy.

    Measured: Up to approximately 7 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2020
  2. Study start19 May 2020
  3. Primary completion31 Jan 2027 (estimated)
  4. Study completion1 Nov 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
520 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04241185
Sponsor's protocol ID
3475-992
Other IDs
MK-3475-992, 205383, U1111-1287-4190, 2023-503500-87-00, jRCT2080225287, 2019-004023-20, 2019, 2023
Status last verified
Apr 2026
First submitted
22 Jan 2020
Last updated
1 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pembrolizumab, Conventional Radiotherapy (Bladder only) and Conventional Radiotherapy (Bladder and pelvic nodes) in people with Urinary Bladder Neoplasms, run by Merck Sharp & Dohme LLC at 134 sites in 25 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 1 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 134 sites in United States, Italy, Romania, Taiwan, Turkey (Türkiye) and 20 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Bladder Intact Event-Free Survival (BI-EFS) (time frame: Up to approximately 76 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04241185.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2026.

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