High-risk Non-muscle Invasive Bladder Cancer Clinical Trial
Official title:
A Phase 3, Randomized, Comparator-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Bacillus Calmette-Guerin (BCG) in Participants With High-risk Non-muscle Invasive Bladder Cancer (HR NMIBC) That is Either Persistent or Recurrent Following BCG Induction or That is Naïve to BCG Treatment (KEYNOTE-676)
This study is designed to assess the antitumor efficacy and safety of pembrolizumab in combination with BCG, compared to BCG monotherapy, in participants with HR NMIBC that is either persistent or recurrent following adequate BCG induction (Cohort A), or that is naïve to BCG treatment (Cohort B). The primary hypothesis for Cohort A is that the combination of pembrolizumab plus BCG has a superior complete response rate (CRR) as assessed by central pathology review compared to BCG in participants with carcinoma in situ (CIS). The primary hypothesis for Cohort B is that the combination of pembrolizumab plus BCG (either reduced maintenance or full maintenance) has a superior Event Free Survival (EFS) compared to BCG.
| Status | Recruiting |
| Enrollment | 1405 |
| Est. completion date | October 12, 2028 |
| Est. primary completion date | December 31, 2025 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Have locally and blinded independent central review (BICR)-confirmed histological diagnosis of high-risk non-muscle invasive (T1, high grade Ta and/or CIS) UC of the bladder - Has undergone cystoscopy/ transurethral resection of bladder tumor (TURBT) to remove all resectable disease - Has provided tissue for biomarker analysis - Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 - Has adequate organ function - During the treatment period and for =7 days after the last dose of BCG, male participants are EITHER abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR, must agree to use contraception unless confirmed to be azoospermic - Female participants who are not pregnant, not breastfeeding, and either not a woman of child bearing potential (WOCBP); or are a WOCBP who agrees to use a contraception method that is highly effective or remains abstinent from heterosexual intercourse during the treatment period and for =7 days after the last dose of BCG or 120 days after the last dose of pembrolizumab, whichever comes last BCG Post-induction Cohort (Cohort A) Only - Has been treated with one adequate course of BCG induction therapy for the treatment of HR NMIBC - Following adequate BCG induction therapy, must have persistent or recurrent HR NMIBC Exclusion Criteria: - Has a history of or concurrent locally advanced (i.e., T2, T3, T4) or metastatic UC - Has concurrent extra-vesical (i.e, urethra, ureter, renal pelvis) non-muscle invasive urothelial carcinoma or a history of extra-vesical non-muscle invasive UC - Has received prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor - Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks of start of study treatment - Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks of start of study treatment - Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days of start of study treatment - Has a known additional malignancy that is progressing or requires active treatment within the past 3 years - Has an active autoimmune disease that has required systemic treatment in past 2 years - Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease - Has one or more of the following contraindications to BCG: prior BCG sepsis or systemic infection, total bladder incontinence, or an adverse experience to a previous BCG instillation that resulted in treatment discontinuation and precludes retreating with BCG - Has an active infection or diagnosis requiring systemic antimicrobial 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 current active tuberculosis - Has had an allogenic-tissue/solid organ transplant - Has any contraindication(s) to IV contrast or is otherwise unable to have screening imaging with IV contrast performed BCG Post-induction Cohort (Cohort A) Only - Has persistent T1 disease following an induction course of BCG BCG Naïve Cohort (Cohort B) Only - Has received any prior treatment with BCG for their NMIBC within the past 2 years prior to study entry |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Epworth Hospital ( Site 0009) | Richmond | Victoria |
| Australia | GenesisCare North Shore ( Site 0010) | St Leonards | New South Wales |
| Australia | Northern Cancer Institute. ( Site 0003) | St Leonards | New South Wales |
| Australia | Sydney Adventist Hospital ( Site 0001) | Wahroonga | New South Wales |
| Austria | Univ. Klinik f. Urologie Innsbruck ( Site 0051) | Innsbruck | Tirol |
| Austria | Ordensklinikum Linz GmbH Elisabethinen ( Site 0052) | Linz | Oberosterreich |
| Austria | Universitaetsklinik Salzburg ( Site 0053) | Salzburg | |
| Austria | Medizinische Universität Wien ( Site 0054) | Vienna | Wien |
| Belgium | O.L.V. Ziekenhuis Aalst ( Site 0106) | Aalst | Oost-Vlaanderen |
| Belgium | UZA University Hospital Antwerp ( Site 0105) | Edegem | Antwerpen |
| Belgium | AZ Maria Middelares Gent ( Site 0102) | Gent | Oost-Vlaanderen |
| Belgium | UZ Gent ( Site 0101) | Gent | Oost-Vlaanderen |
| Belgium | CHU UCL Namur Site de Godinne ( Site 0103) | Yvoir | Namur |
| Brazil | Fundação Pio XII - Hospital de Câncer de Barretos-Unidade de Pesquisa Clínica ( Site 1553) | Barretos | Sao Paulo |
| Brazil | Hospital Erasto Gaertner-CEPEP - Pesquisa Clínica ( Site 1551) | Curitiba | Parana |
| Brazil | Hospital São Carlos-Oncocentro Ce ( Site 1558) | Fortaleza | Ceara |
| Brazil | BP - A Beneficencia Portuguesa de São Paulo ( Site 1559) | Sao Paulo | |
| Brazil | ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 1560) | São Paulo | Sao Paulo |
| Brazil | Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 1554) | São Paulo | Sao Paulo |
| Canada | Exdeo Clinical Research Inc. ( Site 0165) | Abbotsford | British Columbia |
| Canada | CIUSSS du Saguenay-Lac-St-Jean ( Site 0164) | Chicoutimi | Quebec |
| Canada | Horizon Health Network ( Site 0160) | Moncton | New Brunswick |
| Canada | CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0157) | Montreal | Quebec |
| Canada | Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0 | Quebec | |
| Canada | CHUS - Hopital Fleurimont ( Site 0152) | Sherbrooke | Quebec |
| Canada | Princess Margaret Cancer Centre ( Site 0153) | Toronto | Ontario |
| Canada | Silverado Resarch Inc. ( Site 0155) | Victoria | British Columbia |
| China | Beijing Cancer hospital-Urinary Surgery ( Site 1755) | Beijing | Beijing |
| China | Cancer Hospital Chinese Academy of Medical Science-Urinary Surgery ( Site 1766) | Beijing | Beijing |
| China | Peking University First Hospital ( Site 1759) | Beijing | Beijing |
| China | Hunan Cancer Hospital ( Site 1763) | Changsha | Hunan |
| China | West China Hospital Sichuan University ( Site 1767) | Cheng Du | Sichuan |
| China | Chongqing University Cancer Hospital ( Site 1784) | Chongqing | Chongqing |
| China | Sun Yat-sen Memorial Hospital, Sun Yat-sen University-Urology Surgery ( Site 1751) | Guangzhou | Guangdong |
| China | SUN YAT-SEN UNIVERSITY CANCER CENTRE ( Site 1752) | Guangzhou | Guangdong |
| China | The First Affiliated Hospital of Guangzhou Medical University-Urology ( Site 1777) | Guangzhou | Guangdong |
| China | Zhejiang Provincial People's Hospital-Urology ( Site 1762) | Hangzhou | Zhejiang |
| China | Harbin Medical University Cancer Hospital-urology ( Site 1772) | Harbin | Heilongjiang |
| China | Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School-Urology ( S | NanJing | Jiangsu |
| China | ShenZhen People's Hospital ( Site 1778) | Shenzhen | Guangdong |
| China | The Second Affiliated Hospital of Soochow University-Urology ( Site 1773) | Suzhou | Jiangsu |
| China | The Second Hospital of Tianjin Medical University ( Site 1769) | Tianjin | Tianjin |
| China | The First Affiliated Hospital of Wenzhou Medical University-Urology Surgery ( Site 1774) | Wenzhou | Zhejiang |
| China | Tongji Hospital Tongji Medical,Science & Technology ( Site 1768) | Wuhan | Hubei |
| China | Wuhan Union Hospital ( Site 1771) | Wuhan | Hubei |
| China | The First Affiliated Hospital of Xi'an Jiaotong University ( Site 1764) | Xi'an | Shaanxi |
| China | The First Affiliated hospital of Xiamen University-Urology ( Site 1776) | Xiamen | Fujian |
| China | Henan Cancer Hospital-Urology ( Site 1770) | Zhengzhou | Henan |
| Colombia | Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia-Center Investigator ( Site 1605) | Bogota | Distrito Capital De Bogota |
| Colombia | Administradora Country S.A. - Clinica del Country ( Site 1607) | Bogotá | Distrito Capital De Bogota |
| Colombia | Clínica Imbanaco S.A.S ( Site 1611) | Cali | Valle Del Cauca |
| Colombia | Hemato Oncologos SA-Oncology ( Site 1601) | Cali | Valle Del Cauca |
| Colombia | Instituto de Cancerología-Oncology ( Site 1609) | Medellín | Antioquia |
| Colombia | Oncomedica S.A.-Oncomedica S.A ( Site 1604) | Montería | Cordoba |
| Colombia | Oncologos del Occidente ( Site 1608) | Pereira | Risaralda |
| Colombia | Fundación Hospital San Vicente de Paúl - Rionegro - Centros Especializados o de Centros Especializad | Rionegro | Antioquia |
| Costa Rica | Policlinico San Bosco ( Site 0600) | San Jose | |
| Costa Rica | CIMCA ( Site 1550) | San José | San Jose |
| Finland | Tampere University Hospital [Tampere Finland] ( Site 0201) | Tampere | Pirkanmaa |
| France | HENRI MONDOR HOSPITAL ( Site 1357) | Créteil | Seine-et-Marne |
| France | Centre Hospitalier Universitaire Dijon Bourgogne - Hôpital François Mitterrand-Urology ( Site 1355) | Dijon | Bourgogne |
| France | Hopital Claude Huriez - CHU de Lille ( Site 1360) | Lille | Nord |
| France | Centre Hospitalier Universitaire de Rennes - Hôpital Pontchaillou ( Site 1353) | Rennes | Ille-et-Vilaine |
| France | Hôpital Foch-Urology department ( Site 1351) | Suresnes | Hauts-de-Seine |
| Germany | Universitaetsklinikum Jena ( Site 0252) | Jena | Thuringen |
| Germany | Klinikum Rechts der Isar. Technischen Universitaet Muenchen ( Site 0266) | Munich | Bayern |
| Germany | Krankenhaus der Barmherzigen Brüder Trier-Abteilung für Urologie und Kinderurologie ( Site 0262) | Trier | Rheinland-Pfalz |
| Germany | Klinikum Weiden ( Site 0259) | Weiden In Der Oberpfalz | Bayern |
| Germany | Universitaetsklinikum Wuerzburg ( Site 0265) | Wuerzburg | Bayern |
| Greece | ATTIKON GENERAL UNIVERSITY HOSPITAL ( Site 0304) | Chaidari | Attiki |
| Greece | University Hospital of Larissa ( Site 0301) | Larissa | Thessalia |
| Greece | General University Hospital of Patras ( Site 0302) | Patra | Achaia |
| Greece | Olympion General Clinic ( Site 0306) | Patras | Achaia |
| Greece | Antikarkiniko Nosokomeio Thessalonikis THEAGENIO ( Site 0303) | Thessaloniki | Kentriki Makedonia |
| Guatemala | Grupo Medico Angeles ( Site 1453) | Guatemala | |
| Guatemala | INTEGRA Cancer Institute ( Site 1451) | Guatemala | |
| Guatemala | Onco Go, S.A ( Site 1454) | Guatemala City | |
| Hungary | Semmelweis University-Urológiai Klinika ( Site 1301) | Budapest | |
| Hungary | Debreceni Egyetem Klinikai Kozpont ( Site 1302) | Debrecen | |
| Hungary | Pécsi Tudományegyetem Klinikai Központ-Urológiai Klinika ( Site 1304) | Pécs | Baranya |
| Hungary | Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ-Urológiai Klinika ( Site 1303) | Szeged | Csongrad |
| Italy | Azienda USL 8 di Arezzo-Medical Oncology ( Site 0363) | Arezzo | |
| Italy | Istituto Tumori Giovanni Paolo II ( Site 0357) | Bari | |
| Italy | Osp Generale Reg di Bolzano ( Site 0355) | Bolzano | Trentino-Sudtirol |
| Italy | Ospedale Clinicizzato Santissima Annunziata ( Site 0361) | Chieti | Abruzzo |
| Italy | Azienda Ospedaliero Universitaria Careggi ( Site 0360) | Firenze | Toscana |
| Italy | Ospedale San Martino ( Site 0351) | Genova | |
| Italy | Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0353) | Milan | Milano |
| Italy | IRCCS Ospedale San Raffaele ( Site 0362) | Milano | |
| Italy | Ospedale Buccheri La Ferla Fatebenefratelli ( Site 0352) | Palermo | |
| Italy | Policlinico Universitario A. Gemelli ( Site 0358) | Roma | |
| Italy | Ospedale Mauriziano-SCDU ONCOLOGIA MEDICA ( Site 0366) | Torino | Piemonte |
| Italy | A.O.U. di Verona - Ospedale Civile Maggiore Borgo Trento ( Site 0356) | Verona | |
| Japan | Chiba Cancer Center ( Site 0401) | Chiba | |
| Japan | Harasanshin Hospital ( Site 0410) | Fukuoka | |
| Japan | Hamamatsu University Hospital ( Site 0416) | Hamamatsu | Shizuoka |
| Japan | Hirosaki University Hospital ( Site 0407) | Hirosaki | Aomori |
| Japan | Nara Medical University Hospital ( Site 0411) | Kashihara | Nara |
| Japan | St. Marianna University Hospital ( Site 0415) | Kawasaki | Kanagawa |
| Japan | Osaka International Cancer Institute ( Site 0413) | Osaka | |
| Japan | Osaka Metropolitan University Hospital ( Site 0404) | Osaka | |
| Japan | Kitasato University Hospital ( Site 0403) | Sagamihara | Kanagawa |
| Japan | Keio University Hospital ( Site 0405) | Tokyo | |
| Japan | Tokyo Medical and Dental University Hospital ( Site 0409) | Tokyo | |
| Japan | Ehime University Hospital ( Site 0414) | Toon | Ehime |
| Japan | University of Tsukuba Hospital ( Site 0412) | Tsukuba | Ibaraki |
| Japan | Yokosuka Kyosai Hospital ( Site 0406) | Yokosuka | Kanagawa |
| Korea, Republic of | Korea University Anam Hospital ( Site 0801) | Seoul | |
| Korea, Republic of | Samsung Medical Center ( Site 0803) | Seoul | |
| Korea, Republic of | Seoul National University Hospital ( Site 0802) | Seoul | |
| Korea, Republic of | Asan Medical Center ( Site 0804) | Songpagu | Seoul |
| Malaysia | University Malaya Medical Centre ( Site 1180) | Kuala Lumpur | |
| Netherlands | Maastricht University Medical Centre ( Site 0453) | Maastricht | Limburg |
| Netherlands | Erasmus MC ( Site 0451) | Rotterdam | Zuid-Holland |
| Netherlands | Universitair Medisch Centrum Utrecht-Medical Oncology ( Site 0455) | Utrecht | |
| Norway | Akershus University Hospital ( Site 0553) | Lorenskog | Akershus |
| Norway | Stavanger universitetssykehus ( Site 0555) | Stavanger | Rogaland |
| Peru | Hospital Nacional Guillermo Almenara Irigoyen ( Site 0601) | La Victoria | Lima |
| Peru | Hospital Militar Central [Lima, Peru] ( Site 0604) | Lima | |
| Peru | Oncosalud ( Site 0603) | Lima | Muni Metro De Lima |
| Poland | Szpital Specjalistyczny w Koscierzynie Sp. z o.o. ( Site 0671) | Koscierzyna | Pomorskie |
| Poland | Pratia MCM Krakow ( Site 0668) | Krakow | Malopolskie |
| Poland | Clinical Research Center Sp. z o.o. ( Site 0674) | Poznan | Wielkopolskie |
| Poland | Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 0678) | Przemysl | Podkarpackie |
| Poland | LIFTMED ( Site 0652) | Rybnik | Slaskie |
| Poland | Urologica Praktyka Lekarska Adam Marcheluk ( Site 0654) | Siedlce | Mazowieckie |
| Poland | Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku ( Site 0655) | Slupsk | Pomorskie |
| Poland | Szpital Wojewódzki im. Swietego Lukasza SP ZOZ w Tarnowie ( Site 0681) | Tarnow | Malopolskie |
| Poland | MICS Centrum Medyczne Torun ( Site 0679) | Torun | Kujawsko-pomorskie |
| Poland | Medical Concierge Centrum Medyczne ( Site 0676) | Warsaw | Mazowieckie |
| Poland | Luxmed Onkologia sp. z o. o. ( Site 0653) | Warszawa | Mazowieckie |
| Poland | Uniwesytecki Szpital Kliniczny we Wroclawiu ( Site 0669) | Wroclaw | Dolnoslaskie |
| Portugal | 2CA Braga. Centro Clinico Academico ( Site 0705) | Braga | |
| Portugal | Inst. Portugues de Oncologia de Coimbra Francisco Gentil EPE ( Site 0704) | Coimbra | |
| Portugal | CHLN Hospital Santa Maria ( Site 0702) | Lisboa | |
| Portugal | Hospital CUF Descobertas ( Site 0706) | Lisboa | |
| Portugal | Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE ( Site 0708) | Lisboa | |
| Portugal | Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 0701) | Porto | |
| Puerto Rico | Ad-Vance Medical Research ( Site 0756) | Ponce | |
| Puerto Rico | Advance Urology and Laparoscopic Center ( Site 0757) | Ponce | |
| Spain | Fundacio Puigvert ( Site 0864) | Barcelona | |
| Spain | Hospital Universitario Lucus Augusti ( Site 0852) | Lugo | La Coruna |
| Spain | Clinica Universitaria Navarra - Madrid ( Site 0860) | Madrid | |
| Spain | Hospital Universitario Gregorio Maranon ( Site 0854) | Madrid | |
| Spain | Hospital Universitario La Paz ( Site 0866) | Madrid | |
| Spain | Hospital Universitario Ramon y Cajal ( Site 0857) | Madrid | |
| Spain | MD Anderson Cancer Center Madrid ( Site 0859) | Madrid | |
| Spain | Clinica Universitaria de Navarra ( Site 0863) | Pamplona | Navarra |
| Spain | Hospital Universitario Quiron Madrid ( Site 0862) | Pozuelo de Alarcon | Madrid, Comunidad De |
| Spain | Hospital La Fe de Valencia ( Site 0855) | Valencia | |
| Switzerland | Universitaetsspital Basel ( Site 1201) | Basel | Basel-Stadt |
| Switzerland | Hopitaux Universitaires de Geneve HUG ( Site 1204) | Geneve | |
| Switzerland | Universitaetsspital Zurich ( Site 1203) | Zurich | |
| Taiwan | China Medical University Hospital-Department of Urology ( Site 1654) | Taichung | |
| Taiwan | Taichung Veterans General Hospital ( Site 1653) | Taichung | |
| Taiwan | Taipei Veterans General Hospital ( Site 1652) | Taipei | |
| Turkey | Ankara Universitesi Tip Fakultesi Hastanesi ( Site 0966) | Ankara | |
| Turkey | Eskisehir Osmangazi Universitesi Hastanesi ( Site 0953) | Eskisehir | |
| Turkey | Memorial Sisli Hastanesi-Medical Oncology ( Site 0965) | Istanbul | |
| Turkey | TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 0963) | Istanbul | |
| Turkey | Dokuz Eylul Universitesi ( Site 0959) | Izmir | |
| Turkey | Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi ( Site 0961) | Konya | |
| United Kingdom | Raigmore Hospital ( Site 1006) | Inverness | Highland |
| United Kingdom | St Bartholomew s Hospital ( Site 1008) | London | London, City Of |
| United Kingdom | St Georges University Hospitals NHS Foundation Trust. ( Site 1005) | London | London, City Of |
| United States | St. Peter's Hospital Cancer Care Center ( Site 1087) | Albany | New York |
| United States | Alaska Urological Institute dba Alaska Clinical Research Center ( Site 1083) | Anchorage | Alaska |
| United States | Emory School of Medicine ( Site 1076) | Atlanta | Georgia |
| United States | MidLantic Urology ( Site 1071) | Bala-Cynwyd | Pennsylvania |
| United States | Coastal Urology Associates ( Site 1055) | Brick | New Jersey |
| United States | University of Vermont Medical Center ( Site 1057) | Burlington | Vermont |
| United States | Northwestern Memorial Hospital ( Site 1101) | Chicago | Illinois |
| United States | TriState Urologic Services PSC Inc. dba The Urology Group ( Site 1091) | Cincinnati | Ohio |
| United States | University Hospitals Cleveland Medical Center ( Site 1066) | Cleveland | Ohio |
| United States | Ohio State University Arthur G James Cancer Hospital & Richard J Solove Research Institute ( Site 10 | Columbus | Ohio |
| United States | University Of Texas Southwestern Medical Center ( Site 1053) | Dallas | Texas |
| United States | Urology Clinics of North Texas, PLLC ( Site 1064) | Dallas | Texas |
| United States | Henry Ford Health System ( Site 1062) | Detroit | Michigan |
| United States | Texas Oncology-Fort Worth Cancer Center ( Site 8003) | Fort Worth | Texas |
| United States | Urological Research Network ( Site 1106) | Hialeah | Florida |
| United States | Houston Metro Urology ( Site 1111) | Houston | Texas |
| United States | Mayo Clinic in Florida-Urology ( Site 1097) | Jacksonville | Florida |
| United States | Monter Cancer Center ( Site 1080) | Lake Success | New York |
| United States | Colorado Clinical Research ( Site 1100) | Lakewood | Colorado |
| United States | Lancaster Urology ( Site 1079) | Lancaster | Pennsylvania |
| United States | UCLA Hematology/Oncology - Westwood (Building 200 Suite 140)-Department of Urology/Institute of Uro | Los Angeles | California |
| United States | University of Miami Hospital and Clinics, Sylvester Cancer Center ( Site 1056) | Miami | Florida |
| United States | Morristown Medical Center ( Site 1090) | Morristown | New Jersey |
| United States | Carolina Urologic Research Center ( Site 1085) | Myrtle Beach | South Carolina |
| United States | Urology Associates [Nashville, TN] ( Site 1072) | Nashville | Tennessee |
| United States | Rutgers Cancer Institute of New Jersey ( Site 1059) | New Brunswick | New Jersey |
| United States | Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 1074) | New York | New York |
| United States | Veterans Affairs New York Harbor Healthcare System-PCF COE ( Site 1112) | New York | New York |
| United States | University of California Irvine Medical Center ( Site 1061) | Orange | California |
| United States | Woodlands Medical Specialists, PA ( Site 8002) | Pensacola | Florida |
| United States | University of Pennsylvania ( Site 1088) | Philadelphia | Pennsylvania |
| United States | Mayo Clinic in Arizona - Phoenix ( Site 1094) | Phoenix | Arizona |
| United States | Texas Oncology-Plano West ( Site 8001) | Plano | Texas |
| United States | OHSU Knight Cancer Institute ( Site 1075) | Portland | Oregon |
| United States | Advanced Urology ( Site 1092) | Roswell | Georgia |
| United States | Urology San Antonio Research ( Site 1108) | San Antonio | Texas |
| United States | Ochsner LSU Health Shreveport - Regional Urology ( Site 1099) | Shreveport | Louisiana |
| United States | Oregon Urology Institute ( Site 1098) | Springfield | Oregon |
| United States | Associated Medical Professionals of NY ( Site 1078) | Syracuse | New York |
| United States | Genesis Research LLC ( Site 1065) | Torrance | California |
| United States | Michigan Institute of Urology ( Site 1077) | Troy | Michigan |
| United States | Arizona Urology Specialists (AUS)-Professional Park ( Site 1096) | Tucson | Arizona |
| United States | Urology of Virginia ( Site 1070) | Virginia Beach | Virginia |
| United States | Wichita Urology Group ( Site 1086) | Wichita | Kansas |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC |
United States, Australia, Austria, Belgium, Brazil, Canada, China, Colombia, Costa Rica, Finland, France, Germany, Greece, Guatemala, Hungary, Italy, Japan, Korea, Republic of, Malaysia, Netherlands, Norway, Peru, Poland, Portugal, Puerto Rico, Spain, Switzerland, Taiwan, Turkey, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Complete Response Rate (CRR) by Blinded Independent Central Review (BICR) (Cohort A) | CRR is defined as the percentage of participants with CIS achieving a complete response (CR). | Up to ~3.5 years | |
| Primary | Event-Free Survival (EFS) (Cohort B) | EFS is defined as the time from randomization until urothelial carcinoma (UC)-defined event, or death due to any cause. | Up to ~5 years | |
| Secondary | EFS (Cohort A) | EFS is defined as the time from randomization until UC-defined event, or death due to any cause. | Up to ~5 years | |
| Secondary | Recurrence-Free Survival (RFS) (Cohorts A and B) | RFS is defined as the time from randomization until the first occurrence of any UC recurrence, progression, or death due to any cause. | Up to ~5 years | |
| Secondary | Overall Survival (OS) (Cohorts A and B) | OS is defined as the time from randomization to death due to any cause. | Up to ~5 years | |
| Secondary | Disease Specific Survival (DSS) (Cohorts A and B) | DSS is defined as the time from randomization to death due to bladder cancer. | Up to ~5 years | |
| Secondary | Time to Cystectomy (Cohorts A and B) | Time to cystectomy is defined as the time from a participant's randomization until the date of cystectomy. | Up to ~5 years | |
| Secondary | 12-Month EFS Rate (Cohort A) | EFS is defined as the time from randomization until UC-defined event, or death due to any cause. The 12-month EFS rate is defined as the percentage of participants with EFS at 12 months. | 12 months after EFS (up to ~5 years) | |
| Secondary | Duration of Response (DOR) (Cohorts A and B) | DOR is defined as the time from first documented CR until end of response or death due to any cause, whichever occurs first. | Up to ~5 years | |
| Secondary | 12-Month DOR Rate (Cohorts A and B) | The 12-month DOR Rate is defined as the percentage of participants with a CR of at least 12 months duration. | 12 months after CR (up to ~4.5 years) | |
| Secondary | Percentage of Participants Experiencing Adverse Events (AEs) (Cohorts A and B) | An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. | Up to ~5 years | |
| Secondary | Percentage of Participants Discontinuing Study Drug Due to AEs (Cohorts A and B) | An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. | Up to ~5 years | |
| Secondary | Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score (Cohorts A and B) | 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). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. 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. | Baseline, time of last PRO assessment (up to ~2 years) | |
| Secondary | Change from Baseline in EORTC-QLQ-C30 Physical Functioning (Items 1-5) Combined Score (Cohorts A and B) | 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). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. 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. | Baseline, time of last PRO assessment (up to ~2 years) | |
| Secondary | Change from Baseline in EORTC-QLQ-Non-muscle Invasive Bladder Cancer Module 24 (NMIBC24) Total Score (Cohorts A and B) | The EORTC-QLQ-NMIBC24 is a 24-item questionnaire developed to supplement the EORTC QLQ-C30 in high-risk NMIBC patients. Each item is scored out of 4 total points (1=Not at All to 4=Very Much). All responses are transformed from 0 to 100, with a high score indicating more symptoms or problems. The change from baseline in EORTC-QLQ-NMIBC24 total score will be presented. | Baseline, time of last PRO assessment (up to ~2 years) | |
| Secondary | Change from Baseline in European Quality of Life (EuroQoL)-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Visual Analogue Score (VAS) (Cohorts A and B) | 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. | Baseline, time of last PRO assessment (up to ~2 years) | |
| Secondary | Time to Deterioration (TTD) in the EORTC-QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score (Cohorts A and B) | 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). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall outcome. TTD in Global Health Status/Quality of Life is defined as the time from baseline to the first onset of a 10 point or greater decrease from baseline in the Global Health Status/Quality of Life (EORTC QLQ-C30 Items 29 and 30) combined score, with or without subsequent confirmation. | Time of last PRO assessment (up to ~2 years) | |
| Secondary | TTD in the EQ-5D-5L VAS (Cohorts A and B) | The EQ-5D-5L VAS records the respondent's self-rated health on a 20 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". TTD in EQ-5D-5L VAS is defined as the time from baseline to the first onset of a 7 point or greater decrease from baseline in EQ-5D-5L VAS, with or without subsequent confirmation, under a right-censoring rule. | Time of last PRO assessment (up to ~2 years) | |
| Secondary | CRR by BICR (Cohort B) | CRR is defined as the percentage of participants with CIS achieving a CR. | Up to ~3.5 years | |
| Secondary | 24-Month EFS Rate (Cohort B) | EFS is defined as the time from randomization until UC-defined event, or death due to any cause. The 24-month EFS rate is defined as the percentage of participants with EFS at 24 months. | 24 months after EFS (Up to ~5 years) |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT06108492 -
A Phase I Clinical Study of SHR-2005 Intravesical Instillation in the Treatment of High-risk Non-muscle Invasive Bladder Cancer (NMIBC)
|
Phase 1 | |
| Not yet recruiting |
NCT06378242 -
To Evaluate the Safety, Efficacy, and Pharmacokinetics of Intravesical Instiliations of Disitamab Vedotin in Patients With High-risk Non-muscular Invasive Bladder Cancer (NMIBC) That Express HER2
|
Phase 1/Phase 2 |