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ACTIVE NOT RECRUITING

NCT04241185

PHASE3

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)

Sponsor: Merck Sharp & Dohme LLC

View on ClinicalTrials.gov

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). Not all people choose to have surgery and want to keep their bladder using other treatments. 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.

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)

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

520

Start Date

2020-05-19

Completion Date

2031-11-01

Last Updated

2024-11-25

Healthy Volunteers

Conditions

Urinary Bladder Neoplasms

Interventions

DRUG

Pembrolizumab

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

RADIATION

Conventional Radiotherapy (Bladder only)

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

RADIATION

Conventional Radiotherapy (Bladder and pelvic nodes)

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

RADIATION

Hypofractionated Radiotherapy (Bladder only)

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

DRUG

Cisplatin

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

DRUG

Fluorouracil (5-FU)

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.

DRUG

Mitomycin C (MMC)

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

DRUG

Gemcitabine

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

DRUG

Placebo to Pembrolizumab

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

Inclusion Criteria: * 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: * 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 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. * 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

Locations (126)

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

Washington D.C., District of Columbia, United States

Bay Pines VA Medical Center ( Site 0055)

Bay Pines, Florida, United States

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

Orlando, Florida, United States

Norton Cancer Institute ( Site 0044)

Louisville, Kentucky, United States

Pikeville Medical Center ( Site 0009)

Pikeville, Kentucky, United States

Baltimore VA Medical Center ( Site 0054)

Baltimore, Maryland, United States

Washington University ( Site 0003)

St Louis, Missouri, United States

Summit Medical Group Cancer Center ( Site 6008)

Florham Park, New Jersey, United States

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

Hackensack, New Jersey, United States

New York Oncology Hematology P.C ( Site 0024)

Albany, New York, United States

Roswell Park Cancer Institute ( Site 6009)

Buffalo, New York, United States

Winthrop University Hospital ( Site 0069)

Mineola, New York, United States

New York University Perlmutter Cancer Center ( Site 0001)

New York, New York, United States

Fairview Hospital-Moll Cancer Center ( Site 6013)

Cleveland, Ohio, United States

Cleveland Clinic Main ( Site 0062)

Cleveland, Ohio, United States

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

Mayfield Heights, Ohio, United States

MidLantic urology ( Site 0070)

Bala-Cynwyd, Pennsylvania, United States

Saint Francis Cancer Center ( Site 0026)

Greenville, South Carolina, United States

Carolina Urologic Research Center ( Site 0002)

Myrtle Beach, South Carolina, United States

Urology San Antonio Research ( Site 6010)

San Antonio, Texas, United States

Inova Schar Cancer Institute ( Site 6006)

Fairfax, Virginia, United States

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

Charleston, West Virginia, United States

Froedtert and Medical College of Wisconsin ( Site 0022)

Milwaukee, Wisconsin, United States

Liverpool Hospital ( Site 0220)

Liverpool, New South Wales, Australia

GenesisCare North Shore ( Site 0217)

St Leonards, New South Wales, Australia

Monash Medical Centre ( Site 0216)

Clayton, Victoria, Australia

Austin Health ( Site 0218)

Heidelberg, Victoria, Australia

Sir Charles Gairdner Hospital ( Site 0223)

Nedlands, Western Australia, Australia

Oncocentro Valdivia ( Site 7055)

Valdivia, Los Ríos Region, Chile

FALP ( Site 7056)

Santiago, Region M. de Santiago, Chile

Bradfordhill-Clinical Area ( Site 7051)

Santiago, Region M. de Santiago, Chile

ONCOCENTRO APYS-ACEREY ( Site 7054)

Viña del Mar, Región de Valparaíso, Chile

Bradford Hill Norte ( Site 7052)

Antofagasta, Chile

Fakultni nemocnice Olomouc ( Site 0559)

Olomouc, Czechia

2. LF UK a FN Motol ( Site 0555)

Prague, Czechia

Nemocnice Na Bulovce ( Site 0556)

Prague, Czechia

Herlev og Gentofte Hospital. ( Site 0401)

Herlev, Capital Region, Denmark

Odense Universitetshospital ( Site 0403)

Odense, Region Syddanmark, Denmark

North Estonia Medical Centre Foundation ( Site 0081)

Tallinn, Harju, Estonia

Tartu University Hospital ( Site 0079)

Tartu, Tartu, Estonia

Institut Sainte Catherine ( Site 0121)

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

CHU Amiens Picardie Site Sud Amiens ( Site 0123)

Amiens, Somme, France

Institut Curie ( Site 0112)

Paris, France

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

Paris, France

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

Guatemala City, Guatemala

Oncomedica ( Site 0145)

Guatemala City, Guatemala

Grupo Medico Angeles ( Site 0143)

Guatemala City, Guatemala

Medi-K Cayala ( Site 0142)

Guatemala City, Guatemala

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

Quetzaltenango, Guatemala

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

Miskolc, Borsod-Abauj Zemplen county, Hungary

Petz Aladar Megyei Oktato Korhaz ( Site 0099)

Győr, Győr-Moson-Sopron, Hungary

Egeszsegugyi Tudomanyos Tanacs Klinikai Farmakologiai Etikai Bizottsaga ( Site 0095)

Budapest, Hungary

Debreceni Egyetem Klinikai Kozpont ( Site 0097)

Debrecen, Hungary

Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 0091)

Kaposvár, Hungary

Soroka Medical Center-Oncology ( Site 7031)

Beersheba, Israel

Rambam Health Care Campus-Oncology Division ( Site 0088)

Haifa, Israel

Hadassah Medical Center. Ein Kerem ( Site 0086)

Jerusalem, Israel

Rabin Medical Center ( Site 7032)

Petah Tikva, Israel

Chaim Sheba Medical Center ( Site 0087)

Ramat Gan, Israel

Sourasky Medical Center ( Site 0089)

Tel Aviv, Israel

IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 0193)

Bari, Apulia, Italy

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

Rome, Lazio, Italy

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

Milan, Lombardy, Italy

AOU Careggi ( Site 0191)

Florence, Italy

Ospedale Civile di Macerata ( Site 0190)

Macerata, Italy

Ospedale San Raffaele ( Site 0194)

Milan, Italy

Azienda Ospedaliero - Universitaria Policlinico di Modena ( Site 0188)

Modena, Italy

Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0192)

Naples, Italy

Hirosaki University Hospital ( Site 0602)

Hirosaki, Aomori, Japan

University of Tsukuba Hospital ( Site 0605)

Tsukuba, Ibaraki, Japan

Osaka Medical and Pharmaceutical University Hospital ( Site 0604)

Takatsuki, Osaka, Japan

Nagasaki University Hospital ( Site 0600)

Nagasaki, Japan

Institute of Science Tokyo Hospital ( Site 0601)

Tokyo, Japan

Tokyo Metropolitan Komagome Hospital ( Site 0606)

Tokyo, Japan

Pauls Stradins Clinical University Hospital ( Site 0073)

Riga, Latvia

Hospital Universiti Sains Malaysia ( Site 0237)

Kubang Kerian, Kelantan, Malaysia

Hospital Pulau Pinang ( Site 0239)

George Town, Pulau Pinang, Malaysia

Hospital Kuala Lumpur ( Site 0238)

Kuala Lumpur, Malaysia

University Malaya Medical Centre ( Site 0236)

Kuala Lumpur, Malaysia

Netherlands Cancer Institute (NKI) ( Site 0183)

Amsterdam, North Holland, Netherlands

Erasmus MC ( Site 0182)

Rotterdam, South Holland, Netherlands

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

Krakow, Lesser Poland Voivodeship, Poland

Mazowiecki Szpital Wojewódzki w Siedlcach ( Site 0154)

Siedlce, Masovian Voivodeship, Poland

Szpital Wojewodzki im. Mikolaja Kopernika ( Site 0152)

Koszalin, West Pomeranian Voivodeship, Poland

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

Loures, Lisbon District, Portugal

Centro Hospitalar e Universitario de Coimbra ( Site 0306)

Coimbra, Portugal

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

Lisbon, Portugal

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

Lisbon, Portugal

Advance Urology and Laparoscopic Center ( Site 0281)

Ponce, Puerto Rico

PAN American Center Oncologic ( Site 0280)

San Juan, Rio Piedras, Puerto Rico

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

Cluj-Napoca, Cluj, Romania

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

Cluj-Napoca, Cluj, Romania

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

Craiova, Dolj, Romania

Policlinica Oncomed SRL ( Site 0254)

Timișoara, Timiș County, Romania

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

Bucharest, Romania

Institutul Oncologic-Oncologie Medicala ( Site 0256)

Cluj-Napoca, Romania

Institutul Regional de Oncologie Iasi ( Site 0255)

Iași, Romania

National Cancer Center ( Site 0202)

Gyeonggi-do, Kyonggi-do, South Korea

Seoul National University Bundang Hospital ( Site 0204)

Seongnam-si, Kyonggi-do, South Korea

Asan Medical Center ( Site 0200)

Songpagu, Seoul, South Korea

Chungnam National University Hospital ( Site 0203)

Daejeon, Taejon-Kwangyokshi, South Korea

Korea University Anam Hospital ( Site 0205)

Seoul, South Korea

Severance Hospital Yonsei University Health System ( Site 0201)

Seoul, South Korea

Instituto Catalan de Oncologia - ICO ( Site 0103)

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital La Fe de Valencia ( Site 0105)

Valencia, Valenciana, Comunitat, Spain

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

Seville, Spain

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

Ankara, Turkey (Türkiye)

Ankara Universitesi Tip Fakultesi. ( Site 0502)

Ankara, Turkey (Türkiye)

Istanbul Uni. Cerrahpasa Tip Fakultesi ( Site 0501)

Istanbul, Turkey (Türkiye)

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

Istanbul, Turkey (Türkiye)

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

Istanbul, Turkey (Türkiye)

Ege University Medical Faculty ( Site 0508)

Izmir, Turkey (Türkiye)

Karadeniz Teknik Universitesi Tip Fakultesi ( Site 0503)

Trabzon, Turkey (Türkiye)

Clinical oncology dispensary of Dnipro ( Site 0133)

Dnipro, Dnipropetrovsk Oblast, Ukraine

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

Kharkiv, Kharkivs’ka Oblast’, Ukraine

MNPE Regional Center of Oncology ( Site 0134)

Kharkiv, Kharkivs’ka Oblast’, Ukraine

Ukranian Center of TomoTherapy ( Site 0140)

Kropyvnytskiy, Kirovohrad Oblast, Ukraine

SNPE National Cancer Institute ( Site 0136)

Kyiv, Kyivska Oblast, Ukraine

Kyiv City Clinical Oncology Center ( Site 0135)

Kyiv, Ukraine

Betsi Cadwaladr University Health Board ( Site 0447)

Rhyl, Denbighshire, United Kingdom

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

Torquay, Devon, United Kingdom

Royal Preston Hospital ( Site 0449)

Preston, Lancashire, United Kingdom

University College London Hospitals NHS Foundation Trust ( Site 0445)

London, London, City of, United Kingdom

The Royal Marsden NHS Foundation Trust. ( Site 0442)

London, London, City of, United Kingdom

Nottingham University Hospital NHS Trust ( Site 0250)

Nottingham, Nottinghamshire, United Kingdom

Darlington Memorial Hospital NHS Trust ( Site 0446)

Darlington, United Kingdom

Clinical Research Directory

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)

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (126)