Pembrolizumab (MK-3475) Versus Placebo Following Surgery and Radiation in Participants With Locally Advanced Cutaneous Squamous Cell Carcinoma (MK-3475-630/KEYNOTE-630)

Carcinoma, Squamous Cell Clinical Trial

Official title:

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate Pembrolizumab Versus Placebo as Adjuvant Therapy Following Surgery and Radiation in Participants With High-risk Locally Advanced Cutaneous Squamous Cell Carcinoma (LA cSCC) (KEYNOTE-630)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03833167
• Other study ID #: 3475-630
• Secondary ID: MK-3475-630KEYNO
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 1, 2019
• Est. completion date: September 29, 2028

Study information

• Verified date: April 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, double-blind, study that compares pembrolizumab (MK-3475) with placebo given as adjuvant therapy in participants with high-risk locally advanced cutaneous squamous cell carcinoma (LA cSCC) that have undergone surgery with curative intent in combination with radiotherapy. The primary hypothesis is that pembrolizumab is superior to placebo in increasing recurrence free survival (RFS).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 430
• Est. completion date: September 29, 2028
• Est. primary completion date: May 5, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has histologically confirmed cutaneous squamous cell carcinoma (cSCC) as the primary site of malignancy (metastatic skin involvement from another type of primary cancer or from an unknown primary cancer is not permitted)
• Has histologically confirmed LA cSCC with =1 high-risk feature(s) as the primary site of malignancy
• Has undergone complete macroscopic resection of all known cSCC disease with or without microscopic positive margins. For those participants with residual microscopic positive margin involvement, confirmation that additional re-excision is not possible must be provided
• Has completed adjuvant radiotherapy (RT) for LA cSCC with last dose of RT =4 weeks and =16 weeks from randomization
• Has received an adequate post-op dose of RT (either hypofractionated or conventional)
• Is disease free as assessed by the investigator with complete radiographic staging assessment =28 days from randomization
• Is not pregnant or breastfeeding
• Is not a person of childbearing potential (POCBP)
• Has a negative pregnancy test =72 hours before the first dose of study intervention.
• Has provided an archival or newly-obtained tumor tissue sample adequate for Programmed Cell Death Ligand 1 (PD-L1) testing as determined by central laboratory testing
• Has a life expectancy of >3 months
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 =10 days prior to the first dose of study intervention.

Exclusion Criteria:

• Has macroscopic residual cSCC after surgery and/or recurrence with active cSCC disease before randomization
• Has any other histologic type of skin cancer other than invasive cSCC (eg, basal cell carcinoma) that has not been definitively treated with surgery or radiation; Bowen's disease; Merkel cell carcinoma; or melanoma
• Has received prior therapy with an anti-programmed cell death receptor 1(PD-1), anti-PD-L1, or anti-programmed cell death receptor ligand 2 (PD-L2) agent or with an agent directed to another costimulatory or coinhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
• Has received prior systemic anticancer therapy including investigational agents for cSCC =4 weeks prior to before start of study intervention.
• Has not recovered from all radiation-related toxicities and has not had radiation pneumonitis
• Has received a live vaccine =30 days prior to the first dose of study intervention
• Has received an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Has known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Other exceptions may be considered with Sponsor consultation. Note: Participants with low risk early-stage prostate cancer defined as below are not excluded: Stage T1c or T2a with a Gleason score =6 and a prostate-specific antigen (=10 ng/ml) either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to study allocation. Early stage asymptomatic CLL without prior treatment and without any of the risk features (unmutated IGHV, lymphocytes >15,000µL, palpable lymph nodes) will be eligible for the study
• Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid).
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has an active infection requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (HCV; defined as HCV RNA [qualitative] is detected) infection
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention
• Has had an allogeneic tissue/solid organ transplant

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell

Intervention

Biological:
• Pembrolizumab 400 mg
Administered by IV infusion on Day 1 of each 42-day cycle

Drug:
• Placebo
Administered by IV infusion on Day 1 of each 42-day cycle

Locations

Country	Name	City	State
Argentina	CEMIC ( Site 0012)	Buenos Aires
Argentina	Hospital Italiano- Sociedad Italiana de Beneficencia en Buenos Aires ( Site 0009)	Buenos Aires
Argentina	Fundacion CIDEA ( Site 0001)	Caba
Argentina	Centro Medico Privado CEMAIC ( Site 0024)	Capital	Cordoba
Argentina	Centro de Investigaciones Metabólicas (CINME)-Oncology ( Site 0028)	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	Centro Oncologico Riojano Integral ( Site 0002)	La Rioja
Argentina	Centro Oncológico de Rosario ( Site 0003)	Rosario	Santa Fe
Argentina	Fundacion Estudios Clinicos-Oncology ( Site 0026)	Rosario	Santa Fe
Argentina	Centro Oncologico Norte ( Site 0023)	Santiago del Estero
Australia	Chris OBrien Lifehouse ( Site 0051)	Camperdown	New South Wales
Australia	Lismore Base Hospital ( Site 0050)	Lismore	New South Wales
Australia	Alfred Health ( Site 0055)	Melbourne	Victoria
Australia	Orange Health Services ( Site 0053)	Orange	New South Wales
Australia	Gold Coast University Hospital ( Site 0054)	Southport	Queensland
Australia	Royal North Shore Hospital ( Site 0052)	St Leonards	New South Wales
Australia	Sunshine Coast University Private Hospital-Coastal Cancer Care ( Site 0056)	Sunshine Coast	Queensland
Brazil	Hospital Tacchini ( Site 0111)	Bento Goncalves	Rio Grande Do Sul
Brazil	Hospital Erasto Gaertner ( Site 0101)	Curitiba	Parana
Brazil	Oncocentro Ceara ( Site 0108)	Fortaleza	Ceara
Brazil	ONCOSITE - Centro de Pesquisa Clinica em Oncologia ( Site 0100)	Ijui	Rio Grande Do Sul
Brazil	Hospital Bruno Born ( Site 0107)	Lajeado	Rio Grande Do Sul
Brazil	Hospital Sao Vicente de Paulo ( Site 0105)	Passo Fundo	Rio Grande Do Sul
Brazil	Instituto Nacional de Câncer José Alencar Gomes da Silva - INCA-Pesquisa Clinica HC II ( Site 0103)	Rio de Janeiro
Brazil	A. C. Camargo Cancer Center ( Site 0116)	Sao Paulo
Canada	Tom Baker Cancer Center ( Site 0161)	Calgary	Alberta
Canada	Cross Cancer Institute ( Site 0159)	Edmonton	Alberta
Canada	Juravinski Cancer Center ( Site 0151)	Hamilton	Ontario
Canada	CIUSSS de l'Est-de-l'Île-de-Montréal ( Site 0163)	Montreal	Quebec
Canada	McGill University Health Centre ( Site 0162)	Montréal	Quebec
Canada	The Ottawa Hospital Cancer Centre ( Site 0154)	Ottawa	Ontario
Chile	Bradford Hill Norte ( Site 1652)	Antofagasta
Chile	Bradfordhill ( Site 1651)	Santiago	Region M. De Santiago
Chile	Enroll SpA ( Site 1654)	Santiago	Region M. De Santiago
Chile	James Lind Centro de Investigación del Cáncer ( Site 1653)	Temuco	Araucania
Colombia	Instituto Nacional de Cancerologia E.S.E ( Site 0204)	Bogota	Distrito Capital De Bogota
Colombia	Sociedad de Cirugía de Bogotá - Hospital de San Jose ( Site 0201)	Bogota	Distrito Capital De Bogota
Colombia	Fundación Valle del Lili ( Site 0202)	Cali	Valle Del Cauca
Colombia	Oncomedica S.A. ( Site 0205)	Monteria	Cordoba
Colombia	Oncologos del Occidente S.A. ( Site 0206)	Pereira	Risaralda
Colombia	Fundación Cardiovascular de Colombia ( Site 0207)	Piedecuesta	Santander
France	CHU Besancon - Hopital Jean Minjoz ( Site 0359)	Besancon	Doubs
France	Hopital Avicenne ( Site 0358)	Bobigny	Seine-Saint-Denis
France	CHU de Bordeaux- Hopital Saint Andre ( Site 0370)	Bordeaux	Gironde
France	Centre Hospitalier Universitaire de Caen Normandie-DERMATOLOGY ( Site 0365)	Caen	Calvados
France	CHU Estaing ( Site 0360)	Clermont-Ferrand	Puy-de-Dome
France	CHRU de Lille - Hopital Claude Huriez ( Site 0355)	Lille	Nord
France	Hopital La Timone ( Site 0353)	Marseille	Bouches-du-Rhone
France	Hopital Saint Joseph ( Site 0376)	Marseille	Bouches-du-Rhone
France	CHU Montpellier. ( Site 0367)	Montpellier	Herault
France	Hopital ARCHET 2 ( Site 0356)	Nice	Alpes-Maritimes
France	C.H.U. de Nimes. Hopital Caremeau ( Site 0368)	Nimes	Gard
France	CH Lyon Sud Hospices Civils de Lyon ( Site 0350)	Pierre Benite	Rhone
France	CHU Poitiers ( Site 0375)	Poitiers	Vienne
France	Centre Hospitalier Annecy Genevois ( Site 0361)	Pringy	Haute-Savoie
France	Institut Claudius Regaud IUCT Oncopole ( Site 0354)	Toulouse	Haute-Garonne
France	Centre Hospitalier de Valence ( Site 0377)	Valence	Drome
France	Institut Gustave Roussy ( Site 0352)	Villejuif	Val-de-Marne
Germany	Universitaetsklinikum Berlin - Charite - Campus Mitte ( Site 0400)	Berlin
Germany	Elbe Kliniken Stade-Buxtehude, Klinikum Buxtehude-Dermatologisches Zentrum ( Site 0411)	Buxtehude	Niedersachsen
Germany	Universitaetsklinikum Essen ( Site 0403)	Essen	Nordrhein-Westfalen
Germany	Universitaetsklinikum Hamburg-Eppendorf ( Site 0414)	Hamburg
Germany	Medizinische Hochschule Hannover ( Site 0405)	Hannover	Niedersachsen
Germany	Universitatsklinikum Giessen und Marburg GmbH ( Site 0413)	Marburg	Hessen
Germany	Klinikum Nürnberg Nord ( Site 0415)	Nürnberg	Bayern
Germany	Universitaetsklinikum Tuebingen ( Site 0409)	Tuebingen	Baden-Wurttemberg
Greece	Andreas Syggros Hospital ( Site 0450)	Athens	Achaia
Greece	Attikon University General Hospital of Athens ( Site 0454)	Chaidari	Attiki
Greece	Metropolitan Hospital ( Site 0453)	Neo Faliro	Attiki
Greece	European Interbalkan Medical Center ( Site 0455)	Thessaloniki
Greece	Papageorgiou General Hospital ( Site 0451)	Thessaloniki
Hungary	Semmelweis Egyetem ( Site 0507)	Budapest
Hungary	Szent Imre Egyetemi Oktatokorhaz ( Site 0502)	Budapest
Hungary	Debreceni Egyetem. ( Site 0506)	Debrecen	Vas
Hungary	Szabolcs Szatmar Bereg Megyei Korhazak es Egyetemi Oktatokorhaz ( Site 0500)	Nyiregyhaza	Szabolcs-Szatmar-Bereg
Hungary	Pecsi Tudomanyegyetem AOK ( Site 0501)	Pecs	Baranya
Hungary	Szegedi Tudomanyegyetem ( Site 0504)	Szeged	Csongrad
Ireland	St. James s Hospital ( Site 1601)	Dublin 8	Dublin
Israel	Soroka University Medical Center ( Site 0555)	Beer Sheva
Israel	Rambam Health Care Campus-Oncology Division ( Site 0552)	Haifa
Israel	Haddassah Medical Organization - Ein Kerem ( Site 0553)	Jerusalem
Israel	Meir Medical Center ( Site 0556)	Kfar-Saba
Israel	Rabin Medical Center ( Site 0550)	Petah Tiqwa
Israel	Chaim Sheba Medical Center ( Site 0551)	Ramat Gan
Israel	Sourasky Medical Center ( Site 0554)	Tel-Aviv
Italy	Instituto Tumori Giovanni Paolo II ( Site 0604)	Bari	Puglia
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0600)	Milano
Italy	Istituto Europeo di Oncologia ( Site 0602)	Milano
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0601)	Napoli
Italy	Azienda Ospedaliero Universitaria Pisana ( Site 0603)	Pisa	Toscana
Mexico	Centro Estatal de Cancerologia de Chihuahua ( Site 0703)	Chihuahua
Mexico	Consultorios de Medicina Especializada del Sector Privado ( Site 0701)	Guadalajara	Jalisco
Mexico	Hospital de Especialidades Centro Medico de Occidente ( Site 0704)	Guadalajara	Jalisco
Mexico	Onco-Hematologia de Occidente ( Site 0716)	Guadalajara	Jalisco
Mexico	Centro de atencion e investigacion clinica en oncologia ( Site 0706)	Merida	Yucatan
Mexico	Cimab SA de CV ( Site 0708)	Torreon	Coahuila
Mexico	Centro de Investigación Clínica de Alta Especialidad ( Site 0715)	Torreón	Coahuila
Mexico	San Lucas Cardiologica del Sureste S.A de C.V. ( Site 0722)	Tuxtla Gutierrez	Chiapas
Mexico	FAICIC Clinical Research ( Site 0700)	Veracruz
New Zealand	New Zealand Clinical Research (Auckland) ( Site 0800)	Auckland
Norway	Haukeland sykehus ( Site 0851)	Bergen	Hordaland
Norway	Oslo Universitetssykehus Radiumhospitalet ( Site 0850)	Oslo
Norway	St. Olavs Hospital HF ( Site 0852)	Trondheim	Sor-Trondelag
Poland	Uniwersyteckie Centrum Kliniczne-Klinika Chirurgii Onkologicznej, Transplantacyjnej i Ogólnej ( Site	Gdansk	Pomorskie
Poland	Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0958)	Gliwice	Slaskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Oddzial w Krakowie ( Site 0959)	Krakow	Malopolskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0951)	Warszawa	Mazowieckie
Portugal	Hospital Particular do Algarve ( Site 1005)	Faro
Portugal	CHLN Hospital Santa Maria ( Site 1001)	Lisboa
Portugal	Hospital CUF - Tejo ( Site 1004)	Lisboa
Portugal	Instituto Portugues de Oncologia de Lisboa ( Site 1003)	Lisboa
Portugal	Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 1000)	Porto
Romania	Hifu Terramed Conformal SRL ( Site 1111)	Bucharest	Bucuresti
Romania	S.C.Focus Lab Plus S.R.L ( Site 1107)	Bucuresti
Romania	Spitalul de Psihiatrie Titan Dr. Constantin Gorgos ( Site 1112)	Bucuresti
Romania	Cardiomed SRL Cluj-Napoca ( Site 1104)	Cluj-Napoca	Cluj
Romania	Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 1113)	Cluj-Napoca	Cluj
Romania	Spitalul Universitar CF Cluj-Napoca ( Site 1103)	Cluj-Napoca	Cluj
Romania	S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 1101)	Craiova	Dolj
Romania	S C Pelican Impex SRL ( Site 1108)	Oradea	Bihor
Romania	Policlinica Oncomed SRL ( Site 1105)	Timisoara	Timis
Romania	S C Oncocenter Oncologie Medicala S R L ( Site 1106)	Timisoara	Timis
Russian Federation	Udmurtia Republic Regional Clinical Oncology Dispensary ( Site 1158)	Izhevsk	Udmurtskaya Respublika
Russian Federation	First Moscow State Medical University n.a. I.M.Sechenov ( Site 1164)	Moscow	Moskva
Russian Federation	FSCC FMBA of Russia ( Site 1163)	Moscow	Moskva
Russian Federation	Hadassah Medical-Oncology department ( Site 1173)	Moscow	Moskovskaya Oblast
Russian Federation	N.N. Blokhin NMRCO ( Site 1153)	Moscow	Moskva
Russian Federation	Nizhniy Novgorod regional clinical oncological dispensary ( Site 1169)	Nizhny Novgorod	Nizhegorodskaya Oblast
Russian Federation	A. Tsyb Medical Radiological Research Center - branch of the National Medical Research Radiological	Obninsk	Kaluzskaja Oblast
Russian Federation	Railway Hospital of OJSC ( Site 1161)	Saint Petersburg	Sankt-Peterburg
Russian Federation	Oncological Dispensary #2 of Ministry of Health of Krasnodar region ( Site 1159)	Sochi	Krasnodarskiy Kray
Russian Federation	GBUZ Republican Clinical Oncological Dispensary-Antitumor drug therapy department ( Site 1171)	Ufa	Baskortostan, Respublika
Russian Federation	Altay Regional Oncology Dispensary ( Site 1168)	WBarnaularsaw	Altayskiy Kray
Russian Federation	Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 1152)	Yaroslavl	Yaroslavskaya Oblast
Spain	Hospital Clinic i Provincial Barcelona ( Site 1253)	Barcelona	Cataluna
Spain	Hospital General Universitari Vall d Hebron ( Site 1252)	Barcelona
Spain	Onkologikoa - Instituto Oncologico de San Sebastian ( Site 1258)	Doniostia - San Sebastian	Gipuzkoa
Spain	Hospital Duran i Reynals ( Site 1254)	Hospitalet del Llobregat	Barcelona
Spain	Hospital Universitario Ramon y Cajal ( Site 1251)	Madrid
Spain	Hospital Universitario Carlos Haya ( Site 1255)	Malaga
Spain	Hospital Universitario Marques de Valdecilla ( Site 1256)	Santander	Cantabria
Ukraine	Communal Non-Commercial Enterprise "Prykarpatski Clinical On-Department for daily treated patient (	Ivano-Frankivsk	Ivano-Frankivska Oblast
Ukraine	Institute of General and Emergency Surgery named after V.T. Zaitsev NAMS of Ukraine ( Site 1450)	Kharkiv	Kharkivska Oblast
Ukraine	Limited Liability Company Ukrainian Center of Tomotherapy-Department of Chemotherapy ( Site 1451)	Kropyvnytskyi	Kirovohradska Oblast
Ukraine	Universal Clinic Oberig-Oncology Center ( Site 1461)	Kyiv
Ukraine	Sumy regional clinical oncological dispensary-Oncothoracic department ( Site 1452)	Sumy	Sumska Oblast
United Kingdom	Guy s & St Thomas NHS Foundation Trust ( Site 1407)	London	London, City Of
United Kingdom	The Royal Marsden Hospital-Institute of Cancer Research ( Site 1406)	London	London, City Of
United Kingdom	University College Hospital London ( Site 1400)	London	London, City Of
United Kingdom	Churchill Hospital ( Site 1404)	Oxford	Oxfordshire
United Kingdom	Royal Marsden NHS Foundation Trust ( Site 1408)	Sutton	London, City Of
United Kingdom	Royal Cornwall Hospitals NHS Trust ( Site 1402)	Truro	Cornwall
United States	Winship Cancer Institute of Emory University ( Site 1512)	Atlanta	Georgia
United States	University of Colorado Cancer Center ( Site 1506)	Aurora	Colorado
United States	Boca Raton Regional Hospital ( Site 1551)	Boca Raton	Florida
United States	Dana Farber Cancer Center ( Site 1519)	Boston	Massachusetts
United States	Massachusetts General Hospital ( Site 1518)	Boston	Massachusetts
United States	MUSC Hollings Cancer Center ( Site 1533)	Charleston	South Carolina
United States	Cleveland Clinic ( Site 1541)	Cleveland	Ohio
United States	City of Hope Medical Center ( Site 1505)	Duarte	California
United States	Inova Schar Cancer Institute ( Site 1538)	Fairfax	Virginia
United States	UF Health ( Site 1511)	Gainesville	Florida
United States	West Cancer Center - East Campus ( Site 1535)	Germantown	Tennessee
United States	John Theurer Cancer Center at Hackensack University Medical Center ( Site 1526)	Hackensack	New Jersey
United States	The University of Texas-MD Anderson Cancer Center ( Site 1536)	Houston	Texas
United States	Indiana University Melvin and Bren Simon Cancer Center ( Site 1515)	Indianapolis	Indiana
United States	University of Iowa Hospital and Clinics ( Site 1514)	Iowa City	Iowa
United States	UCSD Moores Cancer Center ( Site 1561)	La Jolla	California
United States	Northwell Health/ RJ Zuckerberg Cancer Center-Medical Oncology ( Site 1565)	Lake Success	New York
United States	University of Kentucky School of Medicine & Hospitals ( Site 1542)	Lexington	Kentucky
United States	UCLA Hematology/Oncology - Westwood (Building 100) ( Site 1568)	Los Angeles	California
United States	University of Miami Hospital and Clinics, Sylvester Cancer Center ( Site 1544)	Miami	Florida
United States	University of South Alabama, Mitchell Cancer Institute ( Site 1562)	Mobile	Alabama
United States	West Virginia University ( Site 1569)	Morgantown	West Virginia
United States	Vanderbilt Ingram Cancer Center ( Site 1543)	Nashville	Tennessee
United States	Smilow Cancer Center at Yale-New Haven ( Site 1507)	New Haven	Connecticut
United States	Icahn School of Medicine at Mount Sinai ( Site 1575)	New York	New York
United States	UPMC Hillman Cancer Center ( Site 1570)	Pittsburgh	Pennsylvania
United States	Providence Portland Medical Center ( Site 1530)	Portland	Oregon
United States	University of California Davis Comprehensive Cancer Center ( Site 1560)	Sacramento	California
United States	Huntsman Cancer Institute ( Site 1537)	Salt Lake City	Utah
United States	Stanford University Medical Center ( Site 1503)	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  Chile,  Colombia,  France,  Germany,  Greece,  Hungary,  Ireland,  Israel,  Italy,  Mexico,  New Zealand,  Norway,  Poland,  Portugal,  Romania,  Russian Federation,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence-Free Survival (RFS) as Assessed by the Investigator and Confirmed by Biopsy	RFS was defined as the time between the date of randomization to the date of first local or regional recurrence of the index lesion, distant metastasis, or death due to any cause; whichever occurred first.	Up to approximately 60 months
Secondary	Overall Survival (OS)	OS is the time from randomization to death due to any cause.	Up to approximately 60 months
Secondary	Change From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score	Change from baseline in the score of EORTC QLQ-C30 is reported. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire, which contains 30 items and measures 5 functioning dimensions (physical, role, emotional, cognitive, and social), 3 symptom items (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and QoL scale. Scores ranged from 0 -100. For functional and global quality of life (QoL) scales, higher scores meant a better level of function. For symptom-oriented scales, a higher score meant more severe symptoms and a decrease in QoL.	Baseline and up to approximately 60 months
Secondary	Change From Baseline in Physical Functioning Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 1-5 Score	Change from baseline in the score of EORTC QLQ-C30 Items 1-5 is reported. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. 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. Higher scores meant a better level of function.	Baseline and up to approximately 60 months
Secondary	Percentage of Participants Who Experience an Adverse Event (AE)	An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The percentage of participants who experience at least one AE will be presented.	Up to approximately 63 months
Secondary	Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)	An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The percentage of participants who discontinue study treatment due to an AE will be presented.	Up to approximately 38 months

External Links

•   Merck Clinical Trial Information
•   Plain Language Summary