Perioperative Pembrolizumab (MK-3475) Plus Neoadjuvant Chemotherapy Versus Perioperative Placebo Plus Neoadjuvant Chemotherapy for Cisplatin-eligible Muscle-invasive Bladder Cancer (MIBC) (MK-3475-866/KEYNOTE-866)

Bladder Cancer Clinical Trial

— KEYNOTE-866  

Official title:

A Phase 3, Randomized, Double-blind Study to Evaluate Perioperative Pembrolizumab (MK-3475) + Neoadjuvant Chemotherapy Versus Perioperative Placebo + Neoadjuvant Chemotherapy in Cisplatin-eligible Participants With Muscle-invasive Bladder Cancer (KEYNOTE-866)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03924856
• Other study ID #: 3475-866
• Secondary ID: MK-3475-866KEYNO
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 13, 2019
• Est. completion date: June 15, 2025

Study information

• Verified date: October 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A global study to evaluate peri-operative pembrolizumab with chemotherapy versus placebo to pembrolizumab plus chemotherapy in cisplatin eligible patients.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 907
• Est. completion date: June 15, 2025
• Est. primary completion date: June 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have a histologically confirmed diagnosis of urothelial carcinoma (UC) / muscle invasive bladder cancer (MIBC) (T2-T4aN0M0 or T1-T4aN1M0) with predominant (=50%) urothelial histology.

• Have clinically non-metastatic bladder cancer (N=1 M0) determined by imaging (computed tomography (CT) or magnetic resonance imaging (MRI)) of the chest/abdomen/pelvis.

• Be deemed eligible for Radical Cystectomy (RC) + Pelvic Lymph Node Dissection (PLND).

• Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

• Have adequate organ function.

• Male and female participants are eligible to participate if they agree to the contraception use as per study protocol.

Exclusion Criteria:

• Has a known additional malignancy that is progressing or has required active anti-cancer treatment =3 years of study randomization with certain exceptions.

• Has received any prior systemic treatment for MIBC or non-invasive muscle bladder cancer (NMIBC - prior treatment for NMIBC with intravesical BCG/chemotherapy is permitted) or prior therapy with an anti- programmed cell death 1 (PD-1), anti-programmed cell death ligand 1/ ligand 2 (PD-L1/L2), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4).

• Has =N2 disease or metastatic disease (M1) as identified by imaging.

• Is cisplatin-ineligible, as defined by meeting any one of the cisplatin ineligibility criteria as per protocol.

• Has received prior systemic anticancer therapy including investigational agents within 3 years of randomization or any radiotherapy to the bladder.

• Has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC.

• Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention.

• Has a diagnosis of immunodeficiency or has a known history of human immunodeficiency virus (HIV) infection, Hepatitis B infection or known active Hepatitis C infection.

• Has a known psychiatric or substance abuse disorder.

• Has had an allogenic tissue/solid organ transplant.

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• Pembrolizumab
Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle
• Gemcitabine
Gemcitabine 1000 mg/m^2, IV infusion on Days 1 and 8 of each 21-day cycle
• Cisplatin
Cisplatin 70 mg/m^2, IV infusion on Day 1 of each 21-day cycle

Procedure:
• Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])
Surgical RC+PLND will be done in accordance with the American Urological Association (AUA)/American Society of Clinical Oncology (ASCO)/American Society for Radiation Oncology (ASTRO)/Society of Urologic Oncology (SUO) guidelines.

Drug:
• Placebo
Placebo to pembrolizumab by IV infusion, given on Day 1 of each 21-day cycle

Locations

Country	Name	City	State
Australia	Eastern Health ( Site 1255)	Box Hill	Victoria
Australia	Cairns Base Hospital ( Site 1257)	Cairns	Queensland
Australia	Peninsula Health Frankston Hospital ( Site 1258)	Frankston	Victoria
Australia	Mid North Coast Cancer Institute ( Site 1256)	Port Macquarie	New South Wales
Australia	Southside Cancer Care Centre ( Site 1252)	Sydney	New South Wales
Belgium	O.L.V. Ziekenhuis Aalst ( Site 0356)	Aalst	Oost-Vlaanderen
Belgium	UZ Brussel ( Site 0358)	Brussels	Bruxelles-Capitale, Region De
Belgium	AZ Maria Middelares Gent ( Site 0353)	Gent	Oost-Vlaanderen
Belgium	Jessa Ziekenhuis ( Site 0360)	Hasselt	Limburg
Belgium	CHU UCL Namur Site de Godinne ( Site 0354)	Yvoir	Namur
Canada	Tom Baker Cancer Centre ( Site 0100)	Calgary	Alberta
Canada	Nova Scotia Health Authority ( Site 0109)	Halifax	Nova Scotia
Canada	Kingston Health Sciences Centre ( Site 0103)	Kingston	Ontario
Canada	CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0105)	Montreal	Quebec
Canada	Lakeridge Health ( Site 0104)	Oshawa	Ontario
Canada	Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0	Quebec City	Quebec
Canada	Princess Margaret Cancer Centre ( Site 0107)	Toronto	Ontario
Canada	Sunnybrook Research Institute ( Site 0110)	Toronto	Ontario
Denmark	Herlev og Gentofte Hospital. ( Site 0402)	Herlev	Hovedstaden
Denmark	Rigshospitalet University Hospital ( Site 0401)	Kobenhavn	Hovedstaden
Denmark	Odense Universitetshospital ( Site 0403)	Odense	Syddanmark
France	Institut de Cancerologie de l Ouest Site Paul Papin ( Site 0453)	Angers	Maine-et-Loire
France	Institut Sainte Catherine ( Site 0454)	Avignon	Vaucluse
France	CHU de Bordeaux- Hopital Saint Andre ( Site 0456)	Bordeaux	Aquitaine
France	Centre Francois Baclesse ( Site 0459)	Caen	Calvados
France	Centre Jean Perrin ( Site 0460)	Clermont-Ferrand	Puy-de-Dome
France	Clinique Victor Hugo ( Site 0463)	Le Mans	Sarthe
France	Centre Leon Berard ( Site 0465)	Lyon	Auvergne
France	Hopital Robert Schuman ( Site 0452)	Metz	Moselle
France	CHU de Montpellier - Hopital Saint-Eloi ( Site 0469)	Montpellier	Languedoc-Roussillon
France	Centre Armoricain de Radiotherapie Imagerie medicale et Oncologie ( Site 0457)	Plerin	Cotes-d Armor
France	CHU de Rouen ( Site 0493)	Rouen	Seine-Maritime
France	Hopital Foch ( Site 0483)	Suresnes	Hauts-de-Seine
Germany	Charite Universitaetsmedizin Berlin ( Site 0515)	Berlin
Germany	Vivantes Klinikum am Urban ( Site 0522)	Berlin
Germany	Universitaetsklinikum Carl Gustav Carus ( Site 0519)	Dresden	Sachsen
Germany	Universitaetsklinikum Erlangen ( Site 0505)	Erlangen	Bayern
Germany	Universitaetsklinikum Schleswig-Holstein-Campus Lubeck ( Site 0512)	Luebeck	Schleswig-Holstein
Germany	Universitaetsklinikum Magdeburg A.o.R. ( Site 0516)	Magdeburg	Sachsen-Anhalt
Germany	Klinikum der Eberhard-Karls-Universitaet Tuebingen ( Site 0502)	Tuebingen	Baden-Wurttemberg
Hungary	Bajcsy Zsilinszki Korhaz es Rendelointezet ( Site 1001)	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont ( Site 1006)	Debrecen
Hungary	Petz Aladar Megyei Oktato Korhaz ( Site 1012)	Gyor
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 1007)	Kaposvar
Hungary	Pecsi Tudomanyegyetem AOK ( Site 1009)	Pecs	Baranya
Hungary	SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 1010)	Szeged	Csongrad
Hungary	Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 1002)	Szolnok	Jasz-Nagykun-Szolnok
Ireland	Cork University Hospital ( Site 0722)	Cork
Ireland	Tallaght University Hospital ( Site 0710)	Dublin
Ireland	University Hospital Waterford ( Site 0723)	Waterford
Israel	Ha Emek Medical Center ( Site 0808)	Afula
Israel	Soroka Medical Center ( Site 0806)	Beer Sheva
Israel	Rambam Health Care Campus-Oncology Division ( Site 0802)	Haifa
Israel	Hadassah Ein Kerem Medical Center ( Site 0810)	Jerusalem
Israel	Shaare Zedek Medical Center ( Site 0809)	Jerusalem
Israel	Meir Medical Center ( Site 0803)	Kfar Saba
Israel	Rabin Medical Center ( Site 0804)	Petach Tikva
Israel	Sheba Medical Center ( Site 0801)	Ramat Gan
Israel	Sourasky Medical Center ( Site 0807)	Tel Aviv
Israel	Yitzhak Shamir Medical Center ( Site 0805)	Zerifin
Italy	A.O.U. Policlinico Vittorio Emanuele - Presidio Gaspare Rodolico ( Site 0559)	Catania
Italy	Istituto Nazionale Studio e Cura dei Tumori ( Site 0551)	Milano
Italy	Policlinico di Modena ( Site 0553)	Modena	Emilia-Romagna
Italy	Istituto Nazionale Per Lo Studio E La Cura Dei Tumori ( Site 0552)	Napoli
Italy	Fondazione Salvatore Maugeri IRCCS. ( Site 0554)	Pavia
Italy	Azienda Ospedaliera San Camillo Forlanini ( Site 0560)	Roma
Italy	Policlinico Gemelli di Roma ( Site 0558)	Roma	Abruzzo
Italy	Azienda Ospedaliera Santa Maria Terni ( Site 0557)	Terni
Japan	Chiba Cancer Center ( Site 1506)	Chiba
Japan	Harasanshin Hospital ( Site 1515)	Fukuoka
Japan	Saitama Medical University International Medical Center ( Site 1505)	Hidaka	Saitama
Japan	Hirosaki University Hospital ( Site 1502)	Hirosaki	Aomori
Japan	Hiroshima City Hiroshima Citizens Hospital ( Site 1513)	Hiroshima
Japan	Nara Medical University Hospital ( Site 1510)	Kashihara	Nara
Japan	National Cancer Center Hospital East ( Site 1504)	Kashiwa	Chiba
Japan	Nagano Municipal Hospital ( Site 1516)	Nagano
Japan	Osaka Metropolitan University Hospital ( Site 1512)	Osaka
Japan	Sapporo Medical University Hospital ( Site 1501)	Sapporo	Hokkaido
Japan	Tokushima University Hospital ( Site 1514)	Tokushima
Japan	Tokyo Medical and Dental University Hospital ( Site 1517)	Tokyo
Japan	Ehime University Hospital ( Site 1508)	Toon	Ehime
Japan	University of Tsukuba Hospital ( Site 1503)	Tsukuba	Ibaraki
Japan	Yokosuka Kyosai Hospital ( Site 1509)	Yokosuka	Kanagawa
Korea, Republic of	National Cancer Center ( Site 1354)	Goyang-si	Kyonggi-do
Korea, Republic of	Seoul National University Bundang Hospital ( Site 1356)	Seongnam-si	Kyonggi-do
Korea, Republic of	Asan Medical Center ( Site 1355)	Seoul
Korea, Republic of	Korea University Anam Hospital ( Site 1351)	Seoul
Korea, Republic of	Samsung Medical Center ( Site 1353)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 1352)	Seoul
Mexico	Investigacion Biomedica para el Desarrollo de Farmacos S.A. de C.V. ( Site 0300)	Aguascalientes
Mexico	Centro Estatal de Cancerologia de Chihuahua ( Site 0253)	Chihuahua
Mexico	Centro de Urologia Avanzada del Noreste S.A. de C.V. ( Site 0254)	Monterrey	Nuevo Leon
Mexico	Instituto Nacional de Cancerologia ( Site 0256)	Tlalpan
Poland	Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 1060)	Bielsko-Biala	Slaskie
Poland	Centrum Onkologii im.prof. F. Lukaszczyka w Bydgoszczy ( Site 1068)	Bydgoszcz	Kujawsko-pomorskie
Poland	Europejskie Centrum Zdrowia Otwock ( Site 1057)	Otwock	Mazowieckie
Poland	Luxmed Onkologia sp. z o. o. ( Site 1051)	Warszawa	Mazowieckie
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego ( Site 1062)	Wroclaw	Dolnoslaskie
Russian Federation	Ivanovo Regional Oncology Dispensary ( Site 0852)	Ivanovo	Ivanovskaya Oblast
Russian Federation	Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0861)	Krasnoyarsk	Krasnoyarskiy Kray
Russian Federation	Kursk Regional Clinical Oncology Dispensary ( Site 0854)	Kursk	Kurskaya Oblast
Russian Federation	Central Clinical Hospital with outpatient Clinic ( Site 0856)	Moscow	Moskva
Russian Federation	FSBI ""United Hospital with Polyclinic"" of the Administrative Department of the President of the Ru	Moscow	Moskva
Russian Federation	Bayandin Murmansk Regional Clinical Hospital ( Site 0859)	Murmansk	Murmanskaya Oblast
Russian Federation	Volga District Medical Center Federal Medical and Biological Agency ( Site 0857)	Nizhny Novgorod	Nizhegorodskaya Oblast
Russian Federation	Omsk Clinical Oncology Dispensary ( Site 0865)	Omsk	Omskaya Oblast
Russian Federation	Leningrad Regional Oncology Center ( Site 0868)	Saint Petersburg	Sankt-Peterburg
Russian Federation	Saratov State Medical University n.a. V.I.Razumovskiy ( Site 0866)	Saratov	Saratovskaya Oblast
Russian Federation	Clinical Hospital Saint Luka ( Site 0867)	St. Petersburg	Sankt-Peterburg
Russian Federation	Clinic of Bashkortostan State Medical University ( Site 0869)	Ufa	Baskortostan, Respublika
Spain	Hospital del Mar ( Site 0653)	Barcelona
Spain	Hospital San Pedro de Alcantara ( Site 0654)	Caceres	Extremadura
Spain	H. de Gerona Dr. Josep Trueta ( Site 0651)	Girona	Gerona
Spain	Hospital Universitario La Paz ( Site 0661)	Madrid
Spain	Hospital Universitario Ramon y Cajal ( Site 0660)	Madrid	Madrid, Comunidad De
Spain	Hospital Universitario San Carlos ( Site 0663)	Madrid
Spain	Hospital Universitario Quiron Madrid ( Site 0657)	Pozuelo de Alarcon	Madrid, Comunidad De
Spain	Hospital Nuestra Sra. de Valme ( Site 0658)	Sevilla
Spain	Instituto Valenciano de Oncologia - IVO ( Site 0662)	Valencia	Valenciana, Comunitat
Sweden	Laenssjukhuset Ryhov ( Site 1205)	Jonkoping	Jonkopings Lan
Sweden	Cancercentrum ( Site 1204)	Umea	Vasterbottens Lan
Sweden	Akademiska Sjukhuset ( Site 1201)	Uppsala	Uppsala Lan
Thailand	Faculty of Medicine Siriraj Hospital ( Site 1452)	Bangkok	Krung Thep Maha Nakhon
Thailand	Ramathibodi Hospital. ( Site 1451)	Bangkok	Krung Thep Maha Nakhon
Thailand	Maharaj Nakorn Chiangmai Hospital ( Site 1453)	Chiang Mai
Thailand	Srinagarind Hospital ( Site 1454)	Khon Kaen
Turkey	Hacettepe Universitesi Tip Fakultesi ( Site 0911)	Ankara
Turkey	Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0910)	Istanbul
Turkey	TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 0906)	Istanbul
Turkey	Universitesi Pendik Egitim ve Arastirma Hastanesi ( Site 0901)	Istanbul
Turkey	Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi ( Site 0909)	Konya
Turkey	Sakarya Universitesi Tip Fakultesi ( Site 0913)	Sakarya
Turkey	Karadeniz Teknik Universitesi Tip Fakultesi Farabi Hastanesi ( Site 0904)	Trabzon
Ukraine	Cherkasy Regional Oncology Dispensary ( Site 0959)	Cherkasy	Cherkaska Oblast
Ukraine	Dnipropetrovsk City Multidiscipline Clinical Hosp. 4 of DRC ( Site 0951)	Dnipro	Dnipropetrovska Oblast
Ukraine	Regional Oncological Hospital ( Site 0956)	Dnipro	Dnipropetrovska Oblast
Ukraine	MI Dnipr Regional Clinical Hospital named after I.I. Mechnikov ( Site 0963)	Dnipropetrovsk	Dnipropetrovska Oblast
Ukraine	CNPE "Regional Center of Oncology" ( Site 0958)	Kharkiv	Kharkivska Oblast
Ukraine	Reg. Clinical Center of Urology and Nephrology n.a. V. I. Shapoval ( Site 0969)	Kharkiv	Kharkivska Oblast
Ukraine	Kyiv City Clinical Oncology Center ( Site 0960)	Kyiv
Ukraine	National Cancer Institute of the MoH of Ukraine ( Site 0962)	Kyiv	Kyivska Oblast
Ukraine	Lviv Regional Clinical Hospital ( Site 0955)	Lviv	Lvivska Oblast
Ukraine	Lviv State Oncology Regional Treatment and Diagnostic Center ( Site 0967)	Lviv	Lvivska Oblast
United Kingdom	Aberdeen Royal Infirmary ( Site 0708)	Aberdeen	Aberdeen City
United Kingdom	Kent and Canterbury Hospital ( Site 0709)	Canterbury	England
United Kingdom	Imperial College Healthcare NHS Trust ( Site 0721)	London	London, City Of
United Kingdom	The Royal Marsden Foundation Trust ( Site 0702)	London	London, City Of
United Kingdom	Norfolk & Norwich University Hospital NHS Foundation Trust ( Site 0725)	Norwich	Norfolk
United Kingdom	Lister Hospital ( Site 0715)	Stevenage	Hertfordshire
United Kingdom	Torbay Hospital ( Site 0704)	Torquay	Devon
United Kingdom	Royal Cornwall Hospital ( Site 0703)	Truro
United States	UNM Comprehensive Cancer Center-Clinical Research Office ( Site 0045)	Albuquerque	New Mexico
United States	Charleston Area Medical Center ( Site 0023)	Charles Town	West Virginia
United States	University Hospitals Cleveland Medical Center ( Site 0038)	Cleveland	Ohio
United States	Henry Ford Hospital ( Site 0039)	Detroit	Michigan
United States	Inova Schar Cancer Institute ( Site 0007)	Fairfax	Virginia
United States	Parkview Cancer Institute ( Site 0077)	Fort Wayne	Indiana
United States	MD Anderson Cancer Center ( Site 0063)	Houston	Texas
United States	Indiana University Melvin and Bren Simon Cancer Center ( Site 0004)	Indianapolis	Indiana
United States	Scripps MD Anderson ( Site 0010)	La Jolla	California
United States	Morristown Medical Center ( Site 0015)	Morristown	New Jersey
United States	Ochsner Medical Center ( Site 0049)	New Orleans	Louisiana
United States	New York University Perlmutter Cancer Center ( Site 0008)	New York	New York
United States	AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlando ( Site 0005)	Orlando	Florida
United States	Allegheny General Hospital ( Site 0048)	Pittsburgh	Pennsylvania
United States	Portland VA Medical Center ( Site 0084)	Portland	Oregon
United States	Northwest Medical Specialties, PLLC ( Site 0061)	Puyallup	Washington
United States	Mercy Hospital Saint Louis ( Site 0064)	Saint Louis	Missouri
United States	Providence Saint John's Health Center ( Site 0075)	Santa Monica	California
United States	New England Cancer Specialists ( Site 0070)	Scarborough	Maine
United States	Seattle Cancer Care Alliance/Univ of Washington Medical Center ( Site 0033)	Seattle	Washington
United States	Central Texas Veterans Healthcare System ( Site 0057)	Temple	Texas
United States	Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0021)	Tulsa	Oklahoma
United States	Georgetown University Medical Center ( Site 0022)	Washington	District of Columbia
United States	UMass Memorial Medical Center ( Site 0051)	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Denmark,  France,  Germany,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  Russian Federation,  Spain,  Sweden,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-Free Survival (EFS)	EFS is defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes RC surgery; failure to undergo RC surgery in participants with residual disease and any radiographical disease present; gross residual disease left behind at the time of surgery; local or distant recurrence based on investigator assessments and/or biopsy, or death due to any cause.	Up to approximately 60 months
Secondary	Pathologic Complete Response (pCR) Rate	pCR rate is defined as the percentage of participants having pCR. pCR is defined as absence of viable tumor (pT0N0) in examined tissue from RC and PLND, as assessed by blinded independent central review (BICR).	Up to approximately 72 months
Secondary	Overall Survival (OS)	Overall survival is defined as the time from randomization to death due to any cause.	Up to approximately 72 months
Secondary	Disease-Free Survival (DFS)	DFS is defined as the time from post-surgery baseline scan until the first occurrence of either local or distant recurrence as assessed by investigator by CT or MRI and/or computerized tomography (CT) or magnetic resonance imaging (MRI) and or biopsy or death from any cause.	From approximately 20 weeks up to approximately 72 months
Secondary	Pathologic Downstaging (pDS) Rate	pDS rate is defined as the percentage of participants having pDS. pDS is defined as participants with a tumor classification of	Up to approximately 72 months
Secondary	Number of Participants Who Experienced an Adverse Event (AE)	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to approximately 72 months
Secondary	Number of Participants Who Discontinued Study Treatment Due to an AE	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to approximately 12 months
Secondary	Number of Participants Who Experienced Perioperative Complications	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to approximately 12 months
Secondary	Change in Patient-Reported Outcomes from Baseline in Total Score of Functional Assessment of Cancer Therapy - General (FACT-G)	The FACT-G is a health-related quality of life (HRQoL) 27-item questionnaire in patients being treated for cancer. The FACT-G subscales include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). All items are scored on a 5-point Likert scale of 0 to 4, with higher scores indicating higher HRQoL. The total score can range from 0 to 108.	Baseline, Up to approximately 72 months
Secondary	Change in Patient-Reported Outcomes from Baseline in Total Score of FACT-Bladder- (FACT-BI-Cys)	Total Score of FACT BI-Cys is the sum of FACT-G total score and FACT-Bl-Cys score. FACT-Bl-Cys contains 17 items on the bowel, bladder, and sexual symptoms following cystectomy. The FACT-G is a health-related quality of life (HRQoL) 27-item questionnaire in patients being treated for cancer. The FACT-G subscales include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). All items are scored on a 5-point Likert scale of 0 to 4, with higher scores indicating higher HRQoL. The total score of FACT-Bl-Cys can range from 0 to 168.	Baseline, Up to approximately 72 months
Secondary	Change in Patient-Reported Outcomes from Baseline in FACT-BI-Cys-Trial Outcome Index (TOI)	FACT-Bl-Cys Trial Outcome Index (TOI) is the sum of FACT-G PWB score, FWB score, and FACT-Bl-Cys score. FACT-Bl-Cys contains 17 items on the bowel, bladder, and sexual symptoms following cystectomy. The FACT-G is a health-related quality of life (HRQoL) 27-item questionnaire in patients being treated for cancer. The FACT-G subscales include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). All items are scored on a 5-point Likert scale of 0 to 4, with higher scores indicating higher HRQoL. The total score of FACT-Bl-Cys TOI can range from 0 to 116.	Baseline, Up to approximately 72 months
Secondary	Change in Patient-Reported Outcomes from Baseline in EuroQol Five-Dimensional Questionnaire (EQ-5D-5L) Visual Analog Score (VAS)	The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. In the EQ-5D-5L VAS, the participant rates his or her general state of health at the time of the assessment on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.	Baseline, Up to approximately 72 months
Secondary	Time to Deterioration (TTD) in the Total Score of FACT-G	The FACT-G is a health-related quality of life (HRQoL) 27-item questionnaire in patients being treated for cancer. The FACT-G subscales include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). All items are scored on a 5-point Likert scale of 0-4, with higher scores indicating higher HRQoL. TTD is defined as the time from baseline to the first onset of patient-reported outcomes (PRO) deterioration. For the FACT-G questionnaire, deteriorations are defined as a decrease of 7 points or more (out of 108) from baseline in total score.	Up to approximately 72 months
Secondary	TTD in EQ-5D-5L VAS	The EQ-5D-5L is a standardized instrument for use as a measure of health outcome and includes 5 health state dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. In the EQ-5D-5L VAS, the participant rates his or her general state of health at the time of the assessment on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. TTD is defined as the time from baseline to the first onset of PRO deterioration. For the EQ 5D-5L, deterioration is defined as a decrease of 7 points or more from baseline in the VAS.	Up to approximately 72 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary