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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03553836
Other study ID # 3475-716
Secondary ID MK-3475-716KEYNO
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date September 12, 2018
Est. completion date October 12, 2033

Study information

Verified date February 2024
Source Merck Sharp & Dohme LLC
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This 2-part study will evaluate the safety and efficacy of pembrolizumab (MK-3475) compared to placebo in participants with surgically resected high-risk Stage II melanoma. Participants in Part 1 will receive either pembrolizumab or placebo in a double-blind design every 3 weeks (Q3W) for up to 17 cycles/~1 year (each cycle = 21 days). Participants who complete the initial treatment of 17 cycles of pembrolizumab in Part 1 and experience disease recurrence may be eligible for re-challenge with pembrolizumab at the same dose and schedule of 200 mg Q3W (21-day cycles) for up to 35 cycles (up to ~2 years) in Part 2 in an open label design. Participants who complete the initial treatment of placebo and experience disease recurrence may be eligible to switch over to pembrolizumab 200 mg Q3W (21-day cycles) for up to 35 cycles (up to ~2 years) in Part 2 in an open label design. The primary hypothesis of this study is that pembrolizumab increases recurrence-free survival (RFS) compared to placebo. Per protocol, response/ progression or adverse events (AEs) during re-challenge/switch-over in Part 2 will not be counted towards the RFS outcome measure or safety outcome measures respectively.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 976
Est. completion date October 12, 2033
Est. primary completion date June 21, 2021
Accepts healthy volunteers No
Gender All
Age group 12 Years and older
Eligibility Inclusion: - Has surgically resected and histologically/pathologically confirmed new diagnosis of Stage IIB or IIC cutaneous melanoma per American Joint Committee on Cancer (AJCC) 8th edition guidelines - Has not been previously treated for melanoma beyond complete surgical resection - Has =12 weeks between final surgical resection and randomization - Has no evidence of metastatic disease on imaging as determined by investigator - Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale or Lansky Play-Performance Scale (LPS) score =50 for participants =16 years old, or a Karnofsky Performance Scale (KPS) score =50 for participants >16 and <18 years old - Has recovered adequately from toxicity and/or complications from surgery prior to study start - Female participants must not be pregnant or breastfeeding, and must agree to use contraception during the treatment period and for at least 120 days after the last dose of study treatment if they are women of childbearing potential (WOCBP) Exclusion: - Has a known additional malignancy that is progressing or has required active antineoplastic therapy (including hormonal) within the past 5 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy - Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment - WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required - Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1), anti-Programmed Cell Death Receptor Ligand 1 (PD-L1) or anti-Programmed Cell Death Receptor Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137) - Has received prior systemic anti-cancer therapy for melanoma including investigational agents - Has received a live vaccine within 30 days prior to the first dose 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 prior to the first dose of study treatment - Has severe hypersensitivity (=Grade 3) to any excipients of pembrolizumab - Has an active autoimmune disease that has required systemic treatment in the past 2 years - 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 (defined as hepatitis B surface antigen reactive) or known active hepatitis C virus (defined as hepatitis C virus ribonucleic acid [RNA] [qualitative] is detected) infection - Has a history of active tuberculosis (Bacillus tuberculosis) - Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator - 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 allogeneic tissue/solid organ transplant

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
Pembrolizumab
Administered as an intravenous (IV) infusion every 3 weeks (Q3W)
Other:
Placebo
Administered as an IV infusion every 3 weeks (Q3W)

Locations

Country Name City State
Australia Royal Adelaide Hospital ( Site 0861) Adelaide South Australia
Australia Cairns Base Hospital ( Site 0859) Cairns Queensland
Australia Ashford Cancer Centre Research ( Site 0860) Kurralta Park South Australia
Australia The Alfred Hospital ( Site 0852) Melbourne Victoria
Australia Fiona Stanley Hospital ( Site 0851) Murdoch Western Australia
Australia Melanoma Institute Australia ( Site 0856) North Sydney New South Wales
Australia Tasman Oncology Research Pty Ltd ( Site 0858) Southport Queensland
Australia Westmead Hospital ( Site 0853) Westmead New South Wales
Australia Princess Alexandra Hospital ( Site 0857) Woolloongabba Queensland
Belgium Cliniques Universitaires Saint-Luc ( Site 0251) Brussels Bruxelles-Capitale, Region De
Belgium Institut Jules Bordet ( Site 0254) Bruxelles Bruxelles-Capitale, Region De
Belgium UZ Gent ( Site 0255) Gent Oost-Vlaanderen
Belgium Jessa Ziekenhuis Campus Virga Jesse ( Site 0256) Hasselt Limburg
Belgium UZ Leuven ( Site 0252) Leuven Vlaams-Brabant
Belgium GZA Sint Augustinus ( Site 0259) Wilrijk - Antwerpen Antwerpen
Brazil Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 0155) Barretos Sao Paulo
Brazil Hospital Erasto Gaertner ( Site 0159) Curitiba Parana
Brazil Hospital de Caridade de Ijui ( Site 0156) Ijui Rio Grande Do Sul
Brazil Hospital Sao Vicente de Paulo ( Site 0158) Passo Fundo Rio Grande Do Sul
Brazil Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0154) Porto Alegre Rio Grande Do Sul
Brazil Instituto Nacional do Cancer II ( Site 0160) Rio de Janeiro
Brazil Hospital de Clinicas de Rio Preto ( Site 0162) Sao Jose Do Rio Preto - SP Sao Paulo
Brazil A.C. Camargo Cancer Center ( Site 0164) Sao Paulo
Brazil Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0151) Sao Paulo
Brazil Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 0161) Sao Paulo
Canada Cross Cancer Institute ( Site 0057) Edmonton Alberta
Canada Moncton Hospital - Horizon Health Network ( Site 0055) Moncton New Brunswick
Canada Hopital Maisonneuve Rosemont ( Site 0056) Montreal Quebec
Canada Jewish General Hospital ( Site 0054) Montreal Quebec
Canada McGill University Health Centre ( Site 0062) Montreal Quebec
Canada The Ottawa Hospital ( Site 0058) Ottawa Ontario
Canada CHU de Quebec - Hotel-Dieu de Quebec ( Site 0061) Quebec
Canada Princess Margaret Cancer Centre ( Site 0059) Toronto Ontario
Canada Sunnybrook Research Institute ( Site 0060) Toronto Ontario
Canada CancerCare Manitoba ( Site 0053) Winnipeg Manitoba
Chile Centro Oncologico Antofagasta ( Site 0206) Antofagasta
Chile Fundacion Arturo Lopez Perez FALP ( Site 0200) Santiago Region M. De Santiago
Chile Pontificia Universidad Catolica de Chile ( Site 0201) Santiago Region M. De Santiago
Chile Sociedad Medica Aren y Bachero Limitada ( Site 0207) Santiago Region M. De Santiago
Chile Instituto Clinico Oncologico del Sur ( Site 0203) Temuco Araucania
Chile Oncocentro ( Site 0204) Vina del Mar Valparaiso
France CHU Amiens Picardie Hopital Nord ( Site 0317) Amiens Somme
France CHU Angers ( Site 0321) Angers Maine-et-Loire
France CHU de Bordeaux- Hopital Saint Andre ( Site 0304) Bordeaux Gironde
France Hopital Ambroise Pare Boulogne ( Site 0316) Boulogne-Billancourt Hauts-de-Seine
France CHU Dijon Bourgogne ( Site 0320) Dijon Cote-d Or
France CHRU Lille - Hopital Claude Huriez ( Site 0301) Lille Nord
France Hopital La Timone ( Site 0302) Marseille Bouches-du-Rhone
France CHU Montpellier. ( Site 0312) Montpellier Herault
France Hopital Saint Louis ( Site 0322) Paris
France C.H.U. Lyon Sud ( Site 0303) Pierre Benite Rhone
France CHU de Reims ( Site 0307) Reims Marne
France Centre Eugene Marquis ( Site 0305) Rennes Ille-et-Vilaine
France Institut Claudius Regaud IUCT Oncopole ( Site 0306) Toulouse Haute-Garonne
France Institut Gustave Roussy ( Site 0300) Villejuif Val-de-Marne
Germany Elbe Klinikum Buxtehude ( Site 0354) Buxtehude Niedersachsen
Germany Klinik und Poliklinik fuer Dermatologie Venerologie und Allergologie ( Site 0361) Essen Nordrhein-Westfalen
Germany SRH Wald-Klinikum Gera GmbH ( Site 0360) Gera Thuringen
Germany Universitaetsklinikum Hamburg Eppendorf (UKE) ( Site 0352) Hamburg
Germany Medizinische Hochschule Hannover ( Site 0358) Hannover Niedersachsen
Germany Universitaetsklinikum Schleswig-Holstein Campus Kiel ( Site 0359) Kiel Schleswig-Holstein
Germany Universitaetsklinikum in Mannheim ( Site 0351) Mannheim Baden-Wurttemberg
Germany Klinikum der Ludwig-Maximilians-Universitaet Muenchen ( Site 0357) Muenchen Bayern
Germany Klinikum Nuernberg Nord ( Site 0355) Nuernberg Bayern
Germany Universitaetsklinikum Tuebingen ( Site 0353) Tuebingen Baden-Wurttemberg
Germany Klinikum der Universitaet in Wuerzburg ( Site 0356) Wuerzburg Bayern
Israel HaEmek Medical Center ( Site 0655) Afula
Israel Soroka Medical Center ( Site 0653) Beer Sheva Southern
Israel Rambam Medical Center ( Site 0654) Haifa
Israel Hadassah Ein Kerem Medical Center ( Site 0651) Jerusalem
Israel Chaim Sheba Medical Center. ( Site 0652) Ramat Gan
Israel Sourasky Medical Center ( Site 0656) Tel Aviv Tell Abib
Israel Shamir Medical Center-Assaf Harofeh ( Site 0657) Zerifin
Italy IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 0406) Bari
Italy ASST Papa Giovanni XXIII ( Site 0402) Bergamo
Italy IRCCS A.O.U. San Martino - IST ( Site 0404) Genova
Italy Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST ( Site 0403) Meldola Forli-Cesena
Italy Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0408) Milano
Italy Istituto Nazionale Tumori Fondazione Pascale ( Site 0400) Napoli
Italy IRCCS Istituto Oncologico Veneto ( Site 0407) Padova
Italy IDI - Istituto Dermopatico dell'Immacolata ( Site 0405) Roma
Italy Azienda Ospedaliero Universitaria Senese ( Site 0401) Siena
Japan National Cancer Center Hospital ( Site 0910) Tokyo
Poland Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 0754) Bielsko-Biala Slaskie
Poland Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 0769) Bydgoszcz Kujawsko-pomorskie
Poland Uniwersyteckie Centrum Kliniczne ( Site 0770) Gdansk Pomorskie
Poland Uniwersyteckie Centrum Kliniczne Slaskiego Uniwersytetu Medycznego ( Site 0757) Katowice Slaskie
Poland Pratia MCM Krakow ( Site 0773) Krakow Malopolskie
Poland Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 0753) Poznan Wielkopolskie
Poland LIFTMED ( Site 0765) Rybnik Slaskie
Poland Kliniczny Szpital Wojewodzki Nr 1 ( Site 0758) Rzeszow Podkarpackie
Poland Instytut Pomnik Centrum Zdrowia Dziecka ( Site 0759) Warszawa Mazowieckie
Poland Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0751) Warszawa Mazowieckie
South Africa Cancercare ( Site 0810) Cape Town Limpopo
South Africa Sandton Oncology Medical Group PTY LTD ( Site 0801) Johannesburg Gauteng
South Africa Cape Town Oncology Trials Pty Ltd ( Site 0807) Kraaifontein Western Cape
South Africa Charlotte Maxeke Johannesburg Academic Hospital ( Site 0811) Parktown Gauteng
South Africa Cancer Care Langenhoven Drive Oncology Centre ( Site 0812) Port Elizabeth Eastern Cape
South Africa MPOC ( Site 0803) Pretoria Gauteng
South Africa Wilgers Oncology Centre ( Site 0806) Pretoria Gauteng
Spain Hospital Clinic de Barcelona ( Site 0452) Barcelona
Spain Hospital General Universitari Vall d Hebron ( Site 0456) Barcelona
Spain Hospital General Universitario Gregorio Maranon ( Site 0454) Madrid
Spain Onkologikoa - Instituto Oncologico de San Sebastian ( Site 0457) San Sebastian Gipuzkoa
Spain Hospital Universitario Virgen Macarena ( Site 0455) Sevilla
Spain Hospital General Universitario de Valencia ( Site 0451) Valencia Valenciana, Comunitat
Switzerland Universitaetsspital Basel ( Site 0554) Basel Basel-Stadt
Switzerland Oncological Institute of Southern Switzerland ( Site 0557) Bellinzona Ticino
Switzerland Universitaetsspital Bern ( Site 0552) Bern Berne
Switzerland Kantonsspital Graubuenden ( Site 0555) Chur Grisons
Switzerland Hopitaux Universitaires de Geneve HUG ( Site 0556) Geneva Geneve
Switzerland Centre Hospitalier Universitaire Vaudois ( Site 0553) Lausanne Vaud
Switzerland Hopital du Valais ( Site 0558) Sion Wallis
Switzerland Kantonsspital St. Gallen ( Site 0559) St. Gallen Sankt Gallen
Switzerland Universitaetsspital Zuerich ( Site 0551) Zuerich Zurich
United Kingdom Addenbrooke's Hospital in Cambridge ( Site 0600) Cambridge Cambridgeshire
United Kingdom Guy s & St Thomas NHS Foundation Trust ( Site 0601) London London, City Of
United Kingdom Royal Marsden Hospital - Fulham Road London ( Site 0613) London London, City Of
United Kingdom Christie NHS Foundation Trust ( Site 0604) Manchester
United Kingdom The Royal Marsden NHS Foundation Trust. ( Site 0612) Sutton Surrey
United States Northside Hospital ( Site 0115) Atlanta Georgia
United States Winship Cancer Institute of Emory University ( Site 0046) Atlanta Georgia
United States University of Colorado Cancer Center ( Site 0027) Aurora Colorado
United States Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 0047) Baltimore Maryland
United States Beth Israel Deaconess Medical Center ( Site 0141) Boston Massachusetts
United States Dana Farber Cancer Institute ( Site 0124) Boston Massachusetts
United States Massachusetts General Hospital ( Site 0126) Boston Massachusetts
United States Northwestern Medical Group ( Site 0135) Chicago Illinois
United States The University of Chicago Medical Center ( Site 0007) Chicago Illinois
United States The Lindner Center for Research and Education at The Christ Hospital ( Site 0004) Cincinnati Ohio
United States Karmanos Cancer Institute ( Site 0111) Detroit Michigan
United States Inova Schar Cancer Institute ( Site 0014) Fairfax Virginia
United States West Cancer Center - East Campus ( Site 0022) Germantown Tennessee
United States Memorial Sloan Kettering ( Site 0006) Harrison New York
United States University of Texas-MD Anderson Cancer Center ( Site 0134) Houston Texas
United States University of Iowa Hospital and Clinics ( Site 0001) Iowa City Iowa
United States Mayo Clinic Florida ( Site 0024) Jacksonville Florida
United States University of Tennessee Medical Center Knoxville ( Site 0116) Knoxville Tennessee
United States UCSD Moores Cancer Center ( Site 0133) La Jolla California
United States The Angeles Clinic and Research Institute ( Site 0029) Los Angeles California
United States UCLA Hematology & Oncology ( Site 0130) Los Angeles California
United States University of Wisconsin Hospital and Clinics ( Site 0030) Madison Wisconsin
United States Yale University ( Site 0035) New Haven Connecticut
United States Laura and Isaac Perlmutter Cancer Center ( Site 0137) New York New York
United States Memorial Sloan Kettering Cancer Center ( Site 0142) New York New York
United States Mount Sinai Medical Center ( Site 0038) New York New York
United States Stephenson Cancer Center ( Site 0042) Oklahoma City Oklahoma
United States Advocate Medical Group-Park Ridge ( Site 0025) Park Ridge Illinois
United States Children's Hospital of Pittsburgh UPMC ( Site 0144) Pittsburgh Pennsylvania
United States UPMC Hillman Cancer Centers ( Site 0043) Pittsburgh Pennsylvania
United States Oregon Health & Science University ( Site 0032) Portland Oregon
United States VCU Massey Cancer Center ( Site 0008) Richmond Virginia
United States Mayo Clinic [Rochester, MN] ( Site 0016) Rochester Minnesota
United States University of Rochester ( Site 0019) Rochester New York
United States Siteman Cancer Center ( Site 0143) Saint Louis Missouri
United States John Wayne Cancer Institute ( Site 0026) Santa Monica California
United States Seattle Cancer Care Alliance ( Site 0044) Seattle Washington
United States Moffitt McKinley Outpatient Center ( Site 0131) Tampa Florida
United States University of Arizona Cancer Center ( Site 0121) Tucson Arizona

Sponsors (1)

Lead Sponsor Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  Chile,  France,  Germany,  Israel,  Italy,  Japan,  Poland,  South Africa,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Recurrence-free Survival (RFS) RFS was defined as the time from randomization to any of the following events: recurrence of melanoma at any site (local, in-transit or regional lymph nodes or distant recurrence) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or death due to any cause, whichever occurs first. Per protocol, final analysis for this primary outcome measure was performed using the initial pembrolizumab or placebo treatment with a protocol-specified analysis data cut-off date of June-21-2021. Up to ~32.7 months
Secondary Distant Metastasis-free Survival (DMFS) DMFS will be defined as the time from randomization to the first diagnosis of a distant metastasis per RECIST 1.1. Distant metastasis will refer to cancer that has spread from the original (primary) tumor and beyond local tissues and lymph nodes to distant organs or distant lymph nodes. DMFS will be reported for randomized participants. Up to ~9 years
Secondary Overall Survival (OS) OS will be defined as the time from randomization to death due to any cause. OS will be reported for randomized participants. Up to ~15 years
Secondary Number of Participants Who Experienced at Least One Adverse Event (AE) An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, analysis for this outcome measure was performed using the initial pembrolizumab or placebo treatment. Up to ~19.3 months
Secondary Number of Participants Who Discontinued Study Treatment Due to an AE An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, analysis for this outcome measure was performed using the initial pembrolizumab or placebo treatment. Up to ~19.3 months
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