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

Phase 3

Active, not recruiting

• Conditions: Carcinoma, Squamous Cell
• Interventions: Biological: Pembrolizumab 400 mg; Drug: Placebo

• Registration Number: NCT03833167
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief 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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-02-04
• Study First Submitted QC: 2019-02-04
• Study First Posted: 2019-02-06
• Study Start: 2019-04-01
• Primary Completion: 2024-06-28
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-27
• Last Update Posted: 2024-11-29
• Study Completion: 2025-12-22

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 430

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.

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pembrolizumab	Pembrolizumab 400 mg	Participants receive 400 mg pembrolizumab by intravenous (IV) infusion administered on Day 1 of each 42-day cycle (Q6W) for up to 9 cycles. Participants that complete 9 cycles of pembrolizumab and experience biopsy-proven-disease recurrence may be eligible to receive up to 18 additional cycles of pembrolizumab in an open-label design.
Placebo	Placebo	Participants receive placebo by IV infusion administered on Day 1 of each 42-day cycle (Q6W) for up to 9 cycles. Participants treated with placebo who experience biopsy-proven-disease recurrence may be eligible to receive up to 18 cycles of pembrolizumab in an open-label design.

Primary Outcome Measures

Name	Time	Method
Recurrence-Free Survival (RFS) as Assessed by the Investigator and Confirmed by Biopsy	Up to approximately 60 months	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Up to approximately 60 months	OS is the time from randomization to death due to any cause.
Change From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score	Baseline and up to approximately 60 months	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.
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	Baseline and up to approximately 60 months	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.
Percentage of Participants Who Experience an Adverse Event (AE)	Up to approximately 63 months	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.
Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)	Up to approximately 38 months	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.

Trial Locations

Locations (181)

Winship Cancer Institute of Emory University ( Site 1512); 🇺🇸 Atlanta, Georgia, United States

UPMC Hillman Cancer Center ( Site 1570); 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Miami Hospital and Clinics, Sylvester Cancer Center ( Site 1544); 🇺🇸 Miami, Florida, United States

The University of Texas-MD Anderson Cancer Center ( Site 1536); 🇺🇸 Houston, Texas, United States

Hopital Avicenne ( Site 0358); 🇫🇷 Bobigny, Seine-Saint-Denis, France

Sumy regional clinical oncological dispensary-Oncothoracic department ( Site 1452); 🇺🇦 Sumy, Sumska Oblast, Ukraine

St. James s Hospital ( Site 1601); 🇮🇪 Dublin 8, Dublin, Ireland

City of Hope Medical Center ( Site 1505); 🇺🇸 Duarte, California, United States

West Virginia University ( Site 1569); 🇺🇸 Morgantown, West Virginia, United States

Northwell Health/ RJ Zuckerberg Cancer Center-Medical Oncology ( Site 1565); 🇺🇸 Lake Success, New York, United States

Indiana University Melvin and Bren Simon Cancer Center ( Site 1515); 🇺🇸 Indianapolis, Indiana, United States

Lismore Base Hospital ( Site 0050); 🇦🇺 Lismore, New South Wales, Australia

Royal North Shore Hospital ( Site 0052); 🇦🇺 St Leonards, New South Wales, Australia

Hospital Tacchini ( Site 0111); 🇧🇷 Bento Goncalves, Rio Grande Do Sul, Brazil

Chris OBrien Lifehouse ( Site 0051); 🇦🇺 Camperdown, New South Wales, Australia

Centro Oncologico Riojano Integral ( Site 0002); 🇦🇷 La Rioja, Argentina

Sunshine Coast University Private Hospital-Coastal Cancer Care ( Site 0056); 🇦🇺 Sunshine Coast, Queensland, Australia

CEMIC ( Site 0012); 🇦🇷 Buenos Aires, Argentina

Hospital Erasto Gaertner ( Site 0101); 🇧🇷 Curitiba, Parana, Brazil

Alfred Health ( Site 0055); 🇦🇺 Melbourne, Victoria, Australia

A. C. Camargo Cancer Center ( Site 0116); 🇧🇷 Sao Paulo, Brazil

Instituto Nacional de Câncer José Alencar Gomes da Silva - INCA-Pesquisa Clinica HC II ( Site 0103); 🇧🇷 Rio de Janeiro, Brazil

Fundacion CIDEA ( Site 0001); 🇦🇷 Caba, Argentina

Centro Oncologico Norte ( Site 0023); 🇦🇷 Santiago del Estero, Argentina

ONCOSITE - Centro de Pesquisa Clinica em Oncologia ( Site 0100); 🇧🇷 Ijui, Rio Grande Do Sul, Brazil

Centre Hospitalier Annecy Genevois ( Site 0361); 🇫🇷 Pringy, Haute-Savoie, France

Hospital Sao Vicente de Paulo ( Site 0105); 🇧🇷 Passo Fundo, Rio Grande Do Sul, Brazil

Instituto Nacional de Cancerologia E.S.E ( Site 0204); 🇨🇴 Bogota, Distrito Capital De Bogota, Colombia

Centre Hospitalier Universitaire de Caen Normandie-DERMATOLOGY ( Site 0365); 🇫🇷 Caen, Calvados, France

Hospital Bruno Born ( Site 0107); 🇧🇷 Lajeado, Rio Grande Do Sul, Brazil

Tom Baker Cancer Center ( Site 0161); 🇨🇦 Calgary, Alberta, Canada

Fundación Valle del Lili ( Site 0202); 🇨🇴 Cali, Valle Del Cauca, Colombia

Sociedad de Cirugía de Bogotá - Hospital de San Jose ( Site 0201); 🇨🇴 Bogota, Distrito Capital De Bogota, Colombia

Hopital Saint Joseph ( Site 0376); 🇫🇷 Marseille, Bouches-du-Rhone, France

Centre Hospitalier de Valence ( Site 0377); 🇫🇷 Valence, Drome, France

Hopital La Timone ( Site 0353); 🇫🇷 Marseille, Bouches-du-Rhone, France

Institut Claudius Regaud IUCT Oncopole ( Site 0354); 🇫🇷 Toulouse, Haute-Garonne, France

Universitaetsklinikum Hamburg-Eppendorf ( Site 0414); 🇩🇪 Hamburg, Germany

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

Istituto Europeo di Oncologia ( Site 0602); 🇮🇹 Milano, Italy

Meir Medical Center ( Site 0556); 🇮🇱 Kfar-Saba, Israel

Haukeland sykehus ( Site 0851); 🇳🇴 Bergen, Hordaland, Norway

Onkologikoa - Instituto Oncologico de San Sebastian ( Site 1258); 🇪🇸 Doniostia - San Sebastian, Gipuzkoa, Spain

Udmurtia Republic Regional Clinical Oncology Dispensary ( Site 1158); 🇷🇺 Izhevsk, Udmurtskaya Respublika, Russian Federation

Oncological Dispensary #2 of Ministry of Health of Krasnodar region ( Site 1159); 🇷🇺 Sochi, Krasnodarskiy Kray, Russian Federation

University of South Alabama, Mitchell Cancer Institute ( Site 1562); 🇺🇸 Mobile, Alabama, United States

UCLA Hematology/Oncology - Westwood (Building 100) ( Site 1568); 🇺🇸 Los Angeles, California, United States

UCSD Moores Cancer Center ( Site 1561); 🇺🇸 La Jolla, California, United States

Stanford University Medical Center ( Site 1503); 🇺🇸 Stanford, California, United States

Boca Raton Regional Hospital ( Site 1551); 🇺🇸 Boca Raton, Florida, United States

University of Iowa Hospital and Clinics ( Site 1514); 🇺🇸 Iowa City, Iowa, United States

University of Kentucky School of Medicine & Hospitals ( Site 1542); 🇺🇸 Lexington, Kentucky, United States

Massachusetts General Hospital ( Site 1518); 🇺🇸 Boston, Massachusetts, United States

Dana Farber Cancer Center ( Site 1519); 🇺🇸 Boston, Massachusetts, United States

John Theurer Cancer Center at Hackensack University Medical Center ( Site 1526); 🇺🇸 Hackensack, New Jersey, United States

Cleveland Clinic ( Site 1541); 🇺🇸 Cleveland, Ohio, United States

Icahn School of Medicine at Mount Sinai ( Site 1575); 🇺🇸 New York, New York, United States

West Cancer Center - East Campus ( Site 1535); 🇺🇸 Germantown, Tennessee, United States

Inova Schar Cancer Institute ( Site 1538); 🇺🇸 Fairfax, Virginia, United States

Centro Medico Privado CEMAIC ( Site 0024); 🇦🇷 Capital, Cordoba, Argentina

Fundacion Estudios Clinicos-Oncology ( Site 0026); 🇦🇷 Rosario, Santa Fe, Argentina

Hospital Italiano- Sociedad Italiana de Beneficencia en Buenos Aires ( Site 0009); 🇦🇷 Buenos Aires, Argentina

Oncocentro Ceara ( Site 0108); 🇧🇷 Fortaleza, Ceara, Brazil

Gold Coast University Hospital ( Site 0054); 🇦🇺 Southport, Queensland, Australia

Orange Health Services ( Site 0053); 🇦🇺 Orange, New South Wales, Australia

The Ottawa Hospital Cancer Centre ( Site 0154); 🇨🇦 Ottawa, Ontario, Canada

CIUSSS de l'Est-de-l'Île-de-Montréal ( Site 0163); 🇨🇦 Montreal, Quebec, Canada

Juravinski Cancer Center ( Site 0151); 🇨🇦 Hamilton, Ontario, Canada

Cross Cancer Institute ( Site 0159); 🇨🇦 Edmonton, Alberta, Canada

McGill University Health Centre ( Site 0162); 🇨🇦 Montréal, Quebec, Canada

James Lind Centro de Investigación del Cáncer ( Site 1653); 🇨🇱 Temuco, Araucania, Chile

Bradfordhill ( Site 1651); 🇨🇱 Santiago, Region M. De Santiago, Chile

Bradford Hill Norte ( Site 1652); 🇨🇱 Antofagasta, Chile

Oncomedica S.A. ( Site 0205); 🇨🇴 Monteria, Cordoba, Colombia

C.H.U. de Nimes. Hopital Caremeau ( Site 0368); 🇫🇷 Nimes, Gard, France

CHU de Bordeaux- Hopital Saint Andre ( Site 0370); 🇫🇷 Bordeaux, Gironde, France

CHRU de Lille - Hopital Claude Huriez ( Site 0355); 🇫🇷 Lille, Nord, France

CHU Estaing ( Site 0360); 🇫🇷 Clermont-Ferrand, Puy-de-Dome, France

CHU Montpellier. ( Site 0367); 🇫🇷 Montpellier, Herault, France

CH Lyon Sud Hospices Civils de Lyon ( Site 0350); 🇫🇷 Pierre Benite, Rhone, France

Universitaetsklinikum Tuebingen ( Site 0409); 🇩🇪 Tuebingen, Baden-Wurttemberg, Germany

Universitatsklinikum Giessen und Marburg GmbH ( Site 0413); 🇩🇪 Marburg, Hessen, Germany

Klinikum Nürnberg Nord ( Site 0415); 🇩🇪 Nürnberg, Bayern, Germany

Universitaetsklinikum Essen ( Site 0403); 🇩🇪 Essen, Nordrhein-Westfalen, Germany

Universitaetsklinikum Berlin - Charite - Campus Mitte ( Site 0400); 🇩🇪 Berlin, Germany

Papageorgiou General Hospital ( Site 0451); 🇬🇷 Thessaloniki, Greece

European Interbalkan Medical Center ( Site 0455); 🇬🇷 Thessaloniki, Greece

Pecsi Tudomanyegyetem AOK ( Site 0501); 🇭🇺 Pecs, Baranya, Hungary

Szegedi Tudomanyegyetem ( Site 0504); 🇭🇺 Szeged, Csongrad, Hungary

Debreceni Egyetem. ( Site 0506); 🇭🇺 Debrecen, Vas, Hungary

Semmelweis Egyetem ( Site 0507); 🇭🇺 Budapest, Hungary

Soroka University Medical Center ( Site 0555); 🇮🇱 Beer Sheva, Israel

Haddassah Medical Organization - Ein Kerem ( Site 0553); 🇮🇱 Jerusalem, Israel

Szent Imre Egyetemi Oktatokorhaz ( Site 0502); 🇭🇺 Budapest, Hungary

Sourasky Medical Center ( Site 0554); 🇮🇱 Tel-Aviv, Israel

Chaim Sheba Medical Center ( Site 0551); 🇮🇱 Ramat Gan, Israel

Rabin Medical Center ( Site 0550); 🇮🇱 Petah Tiqwa, Israel

Rambam Health Care Campus-Oncology Division ( Site 0552); 🇮🇱 Haifa, Israel

Instituto Tumori Giovanni Paolo II ( Site 0604); 🇮🇹 Bari, Puglia, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0600); 🇮🇹 Milano, Italy

Azienda Ospedaliero Universitaria Pisana ( Site 0603); 🇮🇹 Pisa, Toscana, Italy

Centro de Investigación Clínica de Alta Especialidad ( Site 0715); 🇲🇽 Torreón, Coahuila, Mexico

Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0601); 🇮🇹 Napoli, Italy

San Lucas Cardiologica del Sureste S.A de C.V. ( Site 0722); 🇲🇽 Tuxtla Gutierrez, Chiapas, 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

Centro de atencion e investigacion clinica en oncologia ( Site 0706); 🇲🇽 Merida, Yucatan, Mexico

FAICIC Clinical Research ( Site 0700); 🇲🇽 Veracruz, Mexico

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Oddzial w Krakowie ( Site 0959); 🇵🇱 Krakow, Malopolskie, Poland

Uniwersyteckie Centrum Kliniczne-Klinika Chirurgii Onkologicznej, Transplantacyjnej i Ogólnej ( Site; 🇵🇱 Gdańsk, Pomorskie, Poland

Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0958); 🇵🇱 Gliwice, Slaskie, Poland

Instituto Portugues de Oncologia de Lisboa ( Site 1003); 🇵🇹 Lisboa, Portugal

CHLN Hospital Santa Maria ( Site 1001); 🇵🇹 Lisboa, Portugal

Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 1000); 🇵🇹 Porto, Portugal

Hifu Terramed Conformal SRL ( Site 1111); 🇷🇴 Bucharest, Bucuresti, Romania

Cardiomed SRL Cluj-Napoca ( Site 1104); 🇷🇴 Cluj-Napoca, Cluj, Romania

S C Oncocenter Oncologie Medicala S R L ( Site 1106); 🇷🇴 Timisoara, Timis, Romania

Altay Regional Oncology Dispensary ( Site 1168); 🇷🇺 WBarnaularsaw, Altayskiy Kray, Russian Federation

A. Tsyb Medical Radiological Research Center - branch of the National Medical Research Radiological; 🇷🇺 Obninsk, Kaluzskaja Oblast, Russian Federation

N.N. Blokhin NMRCO ( Site 1153); 🇷🇺 Moscow, Moskva, Russian Federation

Hadassah Medical-Oncology department ( Site 1173); 🇷🇺 Moscow, Moskovskaya Oblast, Russian Federation

Nizhniy Novgorod regional clinical oncological dispensary ( Site 1169); 🇷🇺 Nizhny Novgorod, Nizhegorodskaya Oblast, Russian Federation

FSCC FMBA of Russia ( Site 1163); 🇷🇺 Moscow, Moskva, Russian Federation

First Moscow State Medical University n.a. I.M.Sechenov ( Site 1164); 🇷🇺 Moscow, Moskva, Russian Federation

Railway Hospital of OJSC ( Site 1161); 🇷🇺 Saint Petersburg, Sankt-Peterburg, Russian Federation

Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 1152); 🇷🇺 Yaroslavl, Yaroslavskaya Oblast, Russian Federation

Hospital Duran i Reynals ( Site 1254); 🇪🇸 Hospitalet del Llobregat, Barcelona, Spain

Hospital Universitario Marques de Valdecilla ( Site 1256); 🇪🇸 Santander, Cantabria, Spain

Hospital Clinic i Provincial Barcelona ( Site 1253); 🇪🇸 Barcelona, Cataluna, Spain

Hospital Universitario Ramon y Cajal ( Site 1251); 🇪🇸 Madrid, Spain

Hospital General Universitari Vall d Hebron ( Site 1252); 🇪🇸 Barcelona, Spain

Hospital Universitario Carlos Haya ( Site 1255); 🇪🇸 Malaga, Spain

Communal Non-Commercial Enterprise "Prykarpatski Clinical On-Department for daily treated patient (; 🇺🇦 Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine

Limited Liability Company Ukrainian Center of Tomotherapy-Department of Chemotherapy ( Site 1451); 🇺🇦 Kropyvnytskyi, Kirovohradska Oblast, Ukraine

University College Hospital London ( Site 1400); 🇬🇧 London, London, City Of, 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

Royal Marsden NHS Foundation Trust ( Site 1408); 🇬🇧 Sutton, London, City Of, United Kingdom

Churchill Hospital ( Site 1404); 🇬🇧 Oxford, Oxfordshire, United Kingdom

Medizinische Hochschule Hannover ( Site 0405); 🇩🇪 Hannover, Niedersachsen, Germany

Elbe Kliniken Stade-Buxtehude, Klinikum Buxtehude-Dermatologisches Zentrum ( Site 0411); 🇩🇪 Buxtehude, Niedersachsen, Germany

New Zealand Clinical Research (Auckland) ( Site 0800); 🇳🇿 Auckland, New Zealand

GBUZ Republican Clinical Oncological Dispensary-Antitumor drug therapy department ( Site 1171); 🇷🇺 Ufa, Baskortostan, Respublika, Russian Federation

UF Health ( Site 1511); 🇺🇸 Gainesville, Florida, United States

CHU Besancon - Hopital Jean Minjoz ( Site 0359); 🇫🇷 Besancon, Doubs, France

Szabolcs Szatmar Bereg Megyei Korhazak es Egyetemi Oktatokorhaz ( Site 0500); 🇭🇺 Nyiregyhaza, Szabolcs-Szatmar-Bereg, Hungary

Oslo Universitetssykehus Radiumhospitalet ( Site 0850); 🇳🇴 Oslo, Norway

Spitalul Universitar CF Cluj-Napoca ( Site 1103); 🇷🇴 Cluj-Napoca, Cluj, Romania

Institut Gustave Roussy ( Site 0352); 🇫🇷 Villejuif, Val-de-Marne, France

Royal Cornwall Hospitals NHS Trust ( Site 1402); 🇬🇧 Truro, Cornwall, United Kingdom

Fundación Cardiovascular de Colombia ( Site 0207); 🇨🇴 Piedecuesta, Santander, Colombia

Centro Estatal de Cancerologia de Chihuahua ( Site 0703); 🇲🇽 Chihuahua, Mexico

St. Olavs Hospital HF ( Site 0852); 🇳🇴 Trondheim, Sor-Trondelag, Norway

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0951); 🇵🇱 Warszawa, Mazowieckie, Poland

Policlinica Oncomed SRL ( Site 1105); 🇷🇴 Timisoara, Timis, Romania

Universal Clinic Oberig-Oncology Center ( Site 1461); 🇺🇦 Kyiv, Ukraine

Hopital ARCHET 2 ( Site 0356); 🇫🇷 Nice, Alpes-Maritimes, France

Hospital CUF - Tejo ( Site 1004); 🇵🇹 Lisboa, Portugal

S C Pelican Impex SRL ( Site 1108); 🇷🇴 Oradea, Bihor, Romania

Oncologos del Occidente S.A. ( Site 0206); 🇨🇴 Pereira, Risaralda, Colombia

Centro de Investigaciones Metabólicas (CINME)-Oncology ( Site 0028); 🇦🇷 Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Enroll SpA ( Site 1654); 🇨🇱 Santiago, Region M. De Santiago, Chile

CHU Poitiers ( Site 0375); 🇫🇷 Poitiers, Vienne, France

Cimab SA de CV ( Site 0708); 🇲🇽 Torreon, Coahuila, Mexico

Hospital Particular do Algarve ( Site 1005); 🇵🇹 Faro, Portugal

Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 1113); 🇷🇴 Cluj-Napoca, Cluj, Romania

S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 1101); 🇷🇴 Craiova, Dolj, Romania

S.C.Focus Lab Plus S.R.L ( Site 1107); 🇷🇴 Bucuresti, Romania

Spitalul de Psihiatrie Titan Dr. Constantin Gorgos ( Site 1112); 🇷🇴 Bucuresti, Romania

Onco-Hematologia de Occidente ( Site 0716); 🇲🇽 Guadalajara, Jalisco, Mexico

University of California Davis Comprehensive Cancer Center ( Site 1560); 🇺🇸 Sacramento, California, United States

University of Colorado Cancer Center ( Site 1506); 🇺🇸 Aurora, Colorado, United States

Smilow Cancer Center at Yale-New Haven ( Site 1507); 🇺🇸 New Haven, Connecticut, United States

Providence Portland Medical Center ( Site 1530); 🇺🇸 Portland, Oregon, United States

Vanderbilt Ingram Cancer Center ( Site 1543); 🇺🇸 Nashville, Tennessee, United States

Huntsman Cancer Institute ( Site 1537); 🇺🇸 Salt Lake City, Utah, United States

MUSC Hollings Cancer Center ( Site 1533); 🇺🇸 Charleston, South Carolina, United States

Centro Oncológico de Rosario ( Site 0003); 🇦🇷 Rosario, Santa Fe, Argentina

Institute of General and Emergency Surgery named after V.T. Zaitsev NAMS of Ukraine ( Site 1450); 🇺🇦 Kharkiv, Kharkivska Oblast, Ukraine