Safety and Efficacy Study of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy (MK-3475-564/KEYNOTE-564)

Phase 3

Active, not recruiting

• Conditions: Renal Cell Carcinoma
• Interventions: Drug: Placebo; Biological: Pembrolizumab

• Registration Number: NCT03142334
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) in the adjuvant treatment of adult participants who have undergone nephrectomy and have intermediate-high risk, high risk, or M1 no evidence of disease (M1 NED) renal cell carcinoma (RCC) with clear cell component.

The primary study hypothesis is that pembrolizumab is superior to placebo with respect to Disease-free Survival (DFS) as assessed by the Investigator in male and female participants with intermediate-high risk, high risk and M1 NED RCC.

Detailed Description

Participants will be assigned to receive study treatment until disease recurrence, unacceptable adverse events (AEs), intercurrent illness that prevents further administration of treatment, Investigator's decision to withdraw the participant, noncompliance with study treatment or procedural requirements, administrative reasons requiring cessation of treatment, or until the participant has received 17 cycles of study treatment (approximately 1 year). Each cycle is 3 weeks long.

With Protocol Amendment 02 (dated 04 Sep 2019), the secondary study objectives for the evaluation of pharmacokinetic (PK) parameters and the presence of pembrolizumab antidrug antibodies (ADA) were reclassified as tertiary study objectives.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2017-05-03
• Study First Submitted QC: 2017-05-03
• Study First Posted: 2017-05-05
• Study Start: 2017-06-09
• Primary Completion: 2020-12-14
• Results First Submitted: 2021-11-29
• Results First Submitted QC: 2021-11-29
• Results First Posted: 2021-12-28
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-08
• Last Update Posted: 2024-11-13
• Study Completion: 2025-12-28

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 994

Inclusion Criteria

• Has histologically confirmed diagnosis of renal cell carcinoma (RCC) with clear cell component with or without sarcomatoid features

• Female participants of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study treatment

• Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study treatment through 120 days after the last dose of study treatment

• Has intermediate-high risk, high risk, or M1 no evidence of disease (NED) RCC as defined by the following pathological tumor-node-metastasis and Fuhrman grading status:

  1. Intermediate-high risk RCC: pT2, Grade 4 or sarcomatoid, N0, M0; pT3, Any Grade, N0, M0
  2. High risk RCC: pT4, Any Grade N0, M0; pT Any stage, Any Grade, N+, M0
  3. M1 NED RCC participants who present not only with the primary kidney tumor but also solid, isolated, soft tissue metastases that can be completely resected at one of the following: the time of nephrectomy (synchronous) or, ≤1 year from nephrectomy (metachronous)

• Has received no prior systemic therapy for advanced RCC

• Has undergone a partial nephroprotective or radical complete nephrectomy (and complete resection of solid, isolated, soft tissue metastatic lesion(s) in M1 NED participants) with negative surgical margins

• Must have undergone a nephrectomy and/or metastasectomy ≥28 days prior to signing informed consent and ≤12 weeks prior to randomization

• Must be tumor-free as assessed by the Investigator and validated by either computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain and chest, abdomen, and pelvis and a bone scan ≤28 days from randomization

• Must have provided adequate tissue per the following: Nephrectomy only: tissue from nephrectomy (required); Synchronous M1 NED: tissue from nephrectomy (required) AND, metastasectomy tissue (if available); Metachronous M1 NED: tissue from metastasectomy (required) AND, nephrectomy tissue (if available)

• Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1

• Has adequate organ function

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Exclusion Criteria

• Has had major surgery, other than nephrectomy and/or resection of pre-existing metastases for M1 NED participants, within 12 weeks prior to randomization
• Has received prior radiotherapy for RCC
• Has pre-existing brain or bone metastatic lesions
• Has residual thrombus post nephrectomy in the vena renalis or vena cava
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy is allowed
• Has a known additional malignancy that is progressing or required active treatment ≤3 years ago. Exceptions include early-stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, in situ prostate cancer, or in situ breast cancer that has undergone potentially curative therapy
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Has an active infection requiring systemic therapy
• Has a history of, or is currently on, dialysis
• Has a known history of human immunodeficiency virus (HIV) infection
• Has known active hepatitis B or hepatitis C virus infection
• Has a known history of active tuberculosis (Bacillus tuberculosis)
• Has had a prior solid organ transplant
• Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
• 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 treatment
• Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand 2 (anti-PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137 [tumor necrosis factor receptor superfamily member 9 (TNFRSF9)]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial
• Has received prior anticancer therapy, monoclonal antibody, chemotherapy, or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer) before first dose of study treatment or not recovered (i.e., must be ≤ Grade 1 or at Baseline) from AEs due to previously administered 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants receive placebo (saline solution) via IV infusion on Day 1 of each 3-week cycle for up to 17 cycles (up to approximately 1 year).
Pembrolizumab	Pembrolizumab	Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 17 cycles (up to approximately 1 year).

Primary Outcome Measures

Name	Time	Method
Disease-free Survival (DFS) as Assessed by the Investigator	Up to approximately 42 months (database cutoff date 14 Dec 2020)	DFS, as assessed by the investigator, is defined as the time from randomization to the first documented local recurrence, distant kidney cancer metastasis(es), or death due to any cause, whichever occurs first. Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastasis status (M0 versus M1 no evidence of disease (NED) by investigator) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0 versus 1), United States (US) participant (Yes versus No) within M0 group by investigator was used to report hazard ratio (HR) and 95% confidence intervals (CIs).

Secondary Outcome Measures

Name	Time	Method
Number of Participants Who Experienced an Adverse Event (AE)	Nonserious AEs: Up to 30 days after last dose of study treatment (Up to approximately 13 months); Serious AEs: Up to 90 days after last dose of study treatment (Up to approximately 15 months)	An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. Participants are monitored for the occurrence of nonserious AEs for up to 30 days after last dose of study treatment and of serious AEs for up to 90 days after last dose of study treatment. The number of participants who experience an AE will be assessed.
Event-Free Survival (EFS) as Assessed by the Blinded Independent Central Review (BICR)	Up to approximately 72 months	EFS is defined as time from randomization to the first documented local recurrence or occurrence of distant kidney cancer metastasis(es) among participants which by BICR were considered disease-free at baseline (M0/M1 NED); or disease progression among participants which by BICR were considered to have baseline disease (M1), or death due to any cause, whichever occurs first.
DFS According to Participant Programmed Cell Death-Ligand 1 (PD-L1) Expression Status (Positive, Negative) as Assessed by the Investigator	Up to approximately 72 months	DFS, as assessed by the investigator, is defined as the time from randomization to the first documented local recurrence, or occurrence of distant kidney cancer metastasis(es), or death due to any cause, whichever occurs first. The PD-L1 expression status is based on combined positive score (CPS). If CPS is ≥ 1, PD-L1 expression status is positive and if the CPS is \<1, PD-L1 expression status is negative.
Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) Total Score	Baseline and Week 52	The QLQ-C30 quality of life (QOL) questionnaire contains 5 functioning scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea and vomiting, and pain) and single symptom items (dyspnoea, loss of appetite, insomnia, constipation and diarrhoea) and perceived financial impact of the disease. Items are scored on a 4-point scale (1=not at all, 2=a little, 3= quite a bit, 4=very much). The QLQC30 also contains 2 global health status scales that use 7-point scale scoring (1=very poor and 7=excellent). The change from baseline in the 2-item global health status/QOL life scale (range: 2-14) will be presented, with a higher score representing a higher QOL.
Overall Survival (OS)	Up to approximately 72 months	OS was defined as the time from randomization to death due to any cause.
Number of Participants Who Discontinued Study Drug Due to an AE	Up to approximately 12 months	An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The number of participants who discontinue study treatment due to an AE will be assessed.
First Local Disease Recurrence-specific Survival (DRSS1) as Assessed by the Investigator	Up to approximately 72 months	DRSS1 is defined as the time from randomization to the first documented local recurrence of RCC as assessed by the investigator. For DRSS1, only local recurrence is counted as an event.
OS According to Participant PD-L1 Expression Status (Positive, Negative)	Up to approximately 72 months	OS is defined as the time from randomization to death due to any cause. The PD-L1 expression status is based on combined positive score (CPS). If CPS is ≥ 1, PD-L1 expression status is positive and if the CPS is \<1, PD-L1 expression status is negative.
Change From Baseline in the Functional Assessment of Cancer Therapy Kidney Symptom Index-Disease Related Symptoms (FKSI-DRS) Index Score	Baseline and Week 52	The FKSI-DRS index consists of a 9-item questionnaire that assesses the extent of participant symptoms from kidney cancer over the previous 7 days. Responses are scored on a 5-point scale (0=Not at all to 4=Very much) and summed to generate an index symptom score. These scores can range from 0 to 36, with a higher score indicating more favorable kidney cancer symptom status. The change from baseline in the FKSI-DRS index score will be presented.
Second Disease Recurrence-Specific Survival (DRSS2) as Assessed by the Investigator	Up to approximately 72 months	DRSS2 is defined as the time from randomization to the first documented local recurrence with visceral lesion or occurrence of distant kidney cancer metastasis(es) with visceral lesion, whichever occurs first, as assessed by the investigator.

Trial Locations

Locations (251)

Fiona Stanley Hospital ( Site 0702); 🇦🇺 Murdoch, Western Australia, Australia

Weinberg Cancer Institute at Franklin Square ( Site 0046); 🇺🇸 Baltimore, Maryland, United States

Beth Israel Deaconess Medical Ctr. ( Site 0044); 🇺🇸 Boston, Massachusetts, United States

Montefiore Medical Center ( Site 0009); 🇺🇸 Bronx, New York, United States

Comprehensive Cancer Centers of Nevada ( Site 8013); 🇺🇸 Las Vegas, Nevada, United States

Oncology Hematology Care, Inc. ( Site 8008); 🇺🇸 Cincinnati, Ohio, United States

Baylor Sammons Cancer Center/ Texas Oncology ( Site 8019); 🇺🇸 Dallas, Texas, United States

University of Iowa Hospital and Clinics ( Site 0031); 🇺🇸 Iowa City, Iowa, United States

Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0052); 🇺🇸 Tulsa, Oklahoma, United States

UT Southwestern Medical Center ( Site 0003); 🇺🇸 Dallas, Texas, United States

Liga Norte Riograndense Contra o Cancer ( Site 1013); 🇧🇷 Natal, Rio Grande Do Norte, Brazil

Park Nicollet Frauenshuh Cancer Center ( Site 0020); 🇺🇸 Saint Louis Park, Minnesota, United States

Universidade de Caxias do Sul ( Site 1004); 🇧🇷 Caxias do Sul, Rio Grande Do Sul, Brazil

IHO Corporation- Utah Cancer Specialists ( Site 0055); 🇺🇸 Salt Lake City, Utah, United States

Arizona Oncology Associates, PC- HAL ( Site 8018); 🇺🇸 Phoenix, Arizona, United States

Urology Associates [Nashville, TN] ( Site 0063); 🇺🇸 Nashville, Tennessee, United States

UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0056); 🇺🇸 San Francisco, California, United States

Karmanos Cancer Institute ( Site 0013); 🇺🇸 Detroit, Michigan, United States

Henry Ford Hospital ( Site 0032); 🇺🇸 Detroit, Michigan, United States

Manatee Medical Research Institute ( Site 0039); 🇺🇸 Bradenton, Florida, United States

Sanatorio Britanico ( Site 1106); 🇦🇷 Rosario, Argentina

Instituto Medico Alexander Fleming ( Site 1105); 🇦🇷 Buenos Aires, Argentina

Quest Research Institute ( Site 0036); 🇺🇸 Royal Oak, Michigan, United States

Istituto Europeo di Oncologia ( Site 2000); 🇮🇹 Milano, Italy

Instituto do Cancer de Sao Paulo - ICESP ( Site 1010); 🇧🇷 Sao Paulo, SP, Brazil

Casa de Saude Santa Marcelina ( Site 1006); 🇧🇷 Sao Paulo, SP, Brazil

CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0118); 🇨🇦 Montreal, Quebec, Canada

Woodlands Medical Specialists, PA ( Site 8021); 🇺🇸 Pensacola, Florida, United States

Dana-Farber Cancer Institute (Boston) ( Site 0007); 🇺🇸 Boston, Massachusetts, United States

Taichung Veterans General Hospital ( Site 0204); 🇨🇳 Taichung, Taiwan

Sapporo Medical University Hospital ( Site 0424); 🇯🇵 Sapporo, Hokkaido, Japan

Fundacion Favaloro ( Site 1110); 🇦🇷 Buenos Aires, Argentina

Centro Oncologico Riojano Integral ( Site 1101); 🇦🇷 La Rioja, Argentina

Dr. Leon Richard Oncology Centre ( Site 0106); 🇨🇦 Moncton, New Brunswick, Canada

Hospital Bruno Born ( Site 1015); 🇧🇷 Lajeado, RS, Brazil

St-Jerome Medical Research Inc ( Site 0103); 🇨🇦 St-Jerome, Quebec, Canada

Instituto Nacional del Cancer ( Site 0912); 🇨🇱 Santiago, Region Metropolitana, Chile

Avera Cancer Institute ( Site 0023); 🇺🇸 Sioux Falls, South Dakota, United States

Sanatorio Parque ( Site 1104); 🇦🇷 Rosario, Santa Fe, Argentina

Box Hill Hospital ( Site 0701); 🇦🇺 Box Hill, Victoria, Australia

Bendigo Cancer Centre ( Site 0704); 🇦🇺 Bendigo, Victoria, Australia

Centro de Investigaciones Clinicas - Clinica Viedma ( Site 1102); 🇦🇷 Viedma, Rio Negro, Argentina

Centro Oncologico de Integracion Regional. COIR ( Site 1109); 🇦🇷 Mendoza, Argentina

Lakeridge Health ( Site 0108); 🇨🇦 Oshawa, Ontario, Canada

Centro Oncologico Antofagasta ( Site 0914); 🇨🇱 Antofagasta, Chile

Instituto Nacional de Cancerologia E.S.E ( Site 0807); 🇨🇴 Bogota, Cundinamarca, Colombia

Keski-Suomen keskussairaala ( Site 2303); 🇫🇮 Jyvaskyla, Finland

Oulun yliopistollinen sairaala - OYS ( Site 2304); 🇫🇮 Oulu, Finland

Universitaetsklinikum Jena. ( Site 2104); 🇩🇪 Jena, Germany

Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST ( Site 2012); 🇮🇹 Meldola, Italy

Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 2003); 🇮🇹 Napoli, Italy

Kagawa University Hospital ( Site 0419); 🇯🇵 Kita-gun, Kagawa, Japan

Juravinski Cancer Centre ( Site 0117); 🇨🇦 Hamilton, Ontario, Canada

Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 1002); 🇧🇷 Barretos, Sao Paulo, Brazil

Fundacao Dr Amaral Carvalho ( Site 1005); 🇧🇷 Jau, Sao Paulo, Brazil

CIUSSS du Saguenay-Lac-St-Jean ( Site 0113); 🇨🇦 Chicoutimi, Quebec, Canada

Iram Cancer Research ( Site 0909); 🇨🇱 Santiago, Chile

Hospital Militar de Santiago ( Site 0911); 🇨🇱 Santiago, Chile

Hospital Clinico Universidad de Chile ( Site 0905); 🇨🇱 Santiago, Chile

St. Vincent Healthcare Frontier Cancer Center ( Site 0008); 🇺🇸 Billings, Montana, United States

CISSS-CA Hotel Dieu de Levis ( Site 0111); 🇨🇦 Lévis, Quebec, Canada

Northwest Cancer Specialists, P.C. ( Site 8006); 🇺🇸 Tigard, Oregon, United States

Instituto de Oncologia de Rosario ( Site 1100); 🇦🇷 Rosario, Argentina

Centro Medico San Roque ( Site 1108); 🇦🇷 Tucuman, Argentina

Hospital Nossa Senhora da Conceicao ( Site 1000); 🇧🇷 Porto Alegre, RS, Brazil

Hospital Regional Rancagua Libertador Bernardo O Higgins ( Site 0910); 🇨🇱 Rancagua, Chile

Clinica de la Costa Ltda. ( Site 0804); 🇨🇴 Barranquilla, Atlantico, Colombia

CHU Saint-Eloi ( Site 2203); 🇫🇷 Montpellier, France

Centre Antoine Lacassagne ( Site 2211); 🇫🇷 Nice, France

Universitaetsklinikum Bonn ( Site 2110); 🇩🇪 Bonn, Germany

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz ( Site 2111); 🇩🇪 Mainz, Germany

London Regional Cancer Program - London HSC ( Site 0107); 🇨🇦 London, Ontario, Canada

William Osler Health System ( Site 0115); 🇨🇦 Brampton, Ontario, Canada

St Vincents University Hospital ( Site 1610); 🇮🇪 Dublin, Ireland

Medical Oncology Ospedale San Donato ( Site 2004); 🇮🇹 Arezzo, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 2005); 🇮🇹 Milano, Italy

Nara Medical University Hospital ( Site 0416); 🇯🇵 Kashihara, Nara, Japan

Saitama Medical University International Medical Center ( Site 0404); 🇯🇵 Hidaka, Saitama, Japan

Allan Blair Cancer Centre ( Site 0116); 🇨🇦 Regina, Saskatchewan, Canada

Universitaetsklinikum Hamburg-Eppendorf ( Site 2118); 🇩🇪 Hamburg, Germany

Pontificia Universidad Catolica de Chile ( Site 0904); 🇨🇱 Santiago, Chile

TAYS ( Site 2301); 🇫🇮 Tampere, Finland

TYKS ( Site 2302); 🇫🇮 Turku, Finland

Hopital La Timone ( Site 2204); 🇫🇷 Marseille, France

Centre Eugene Marquis ( Site 2209); 🇫🇷 Rennes, France

Centre Rene Gauducheau ICO ( Site 2207); 🇫🇷 Saint Herblain, France

Universitatsklinikum Dusseldorf ( Site 2108); 🇩🇪 Dusseldorf, Germany

Universitaetsklinikum Erlangen. Waldkrankenhaus ( Site 2102); 🇩🇪 Erlangen, Germany

Amphia Ziekenhuis Breda ( Site 1901); 🇳🇱 Breda, Netherlands

Wojewodzkie Centrum Onkologii Copernicus ( Site 1304); 🇵🇱 Gdansk, Poland

Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli ( Site 1315); 🇵🇱 Lublin, Poland

Severance Hospital Yonsei University Health System ( Site 0303); 🇰🇷 Seoul, Korea, Republic of

Institut Claudius Regaud IUCT Oncopole ( Site 2201); 🇫🇷 Toulouse, France

Hopital Saint Andre ( Site 2202); 🇫🇷 Bordeaux, France

Universitaetsklinikum Essen ( Site 2116); 🇩🇪 Essen, Germany

Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 2006); 🇮🇹 Modena, Italy

Harasanshin Hospital ( Site 0402); 🇯🇵 Fukuoka, Japan

Osaka City University Hospital ( Site 0428); 🇯🇵 Osaka, Japan

Maastricht Universitair Medisch Centrum - MUMC ( Site 1902); 🇳🇱 Maastricht, Netherlands

Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina ( Site 1324); 🇵🇱 Otwock, Poland

Ivanovo Regional Oncology Dispensary ( Site 1204); 🇷🇺 Ivanovo, Russian Federation

Tomsk Scientific Research Institute of Oncology ( Site 1208); 🇷🇺 Tomsk, Russian Federation

Sociedad de Hematologia y Oncologia del Cesar ( Site 0809); 🇨🇴 Valledupar, Cesar, Colombia

University Hospital Waterford ( Site 1614); 🇮🇪 Waterford, Ireland

Nagoya University Hospital ( Site 0431); 🇯🇵 Nagoya, Aichi, Japan

Yamaguchi University Hospital ( Site 0406); 🇯🇵 Ube, Yamaguchi, Japan

Nagano Municipal Hospital ( Site 0429); 🇯🇵 Nagano, Japan

Niigata University Medical & Dental Hospital ( Site 0421); 🇯🇵 Niigata, Japan

Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny ( Site 1309); 🇵🇱 Brzozow, Poland

Szpital Morski im. PCK Szpitale Wojewodzkie w Gdyni Sp. z o.o. ( Site 1302); 🇵🇱 Gdynia, Poland

Omsk Clinical Oncology Dispensary ( Site 1209); 🇷🇺 Omsk, Russian Federation

China Medical University Hospital ( Site 0200); 🇨🇳 Taichung, Taiwan

Kumamoto University Hospital ( Site 0434); 🇯🇵 Kumamoto, Japan

Franciscus Gasthuis ( Site 1903); 🇳🇱 Rotterdam, Netherlands

Szpital Specjalistyczny w Koscierzynie Sp. z o.o. ( Site 1322); 🇵🇱 Koscierzyna, Pomorskie, Poland

Przychodnia Lekarska Komed ( Site 1306); 🇵🇱 Konin, Poland

Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1217); 🇷🇺 Ufa, Russian Federation

National Medical Research Radiology Centre ( Site 1200); 🇷🇺 Moscow, Russian Federation

National Taiwan University Hospital ( Site 0202); 🇨🇳 Taipei, Taiwan

Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 1210); 🇷🇺 Krasnoyarsk, Russian Federation

Russian Scientific Center of Radiology and Surgical Technologies ( Site 1205); 🇷🇺 Saint Petersburg, Russian Federation

Chang Gung Medical Foundation. Linkou ( Site 0203); 🇨🇳 Taoyuan, Taiwan

Taipei Veterans General Hospital ( Site 0201); 🇨🇳 Taipei, Taiwan

Nebraska Cancer Specialists ( Site 0012); 🇺🇸 Omaha, Nebraska, United States

Rocky Mountain Cancer Center ( Site 8010); 🇺🇸 Aurora, Colorado, United States

University of Michigan ( Site 0045); 🇺🇸 Ann Arbor, Michigan, United States

USC Norris Comprehensive Cancer Center ( Site 0038); 🇺🇸 Los Angeles, California, United States

Sansum Clinic Research ( Site 8014); 🇺🇸 Santa Barbara, California, United States

Stanford Cancer Center ( Site 0028); 🇺🇸 Stanford, California, United States

Boca Raton Regional Hospital- Lynn Cancer Institute ( Site 0035); 🇺🇸 Boca Raton, Florida, United States

Illinois Cancer Specialists ( Site 8001); 🇺🇸 Niles, Illinois, United States

McFarland Clinic ( Site 0025); 🇺🇸 Ames, Iowa, United States

Maryland Oncology Hematology, P.A. ( Site 8020); 🇺🇸 Rockville, Maryland, United States

Fairview Southdale Medical Oncology Clinic ( Site 0041); 🇺🇸 Edina, Minnesota, United States

Minnesota Oncology Specialist, PA ( Site 8002); 🇺🇸 Minneapolis, Minnesota, United States

University of New Mexico Cancer Center ( Site 0043); 🇺🇸 Albuquerque, New Mexico, United States

Duke University ( Site 0037); 🇺🇸 Durham, North Carolina, United States

St. Luke's University Health Network ( Site 0042); 🇺🇸 Easton, Pennsylvania, United States

Abramson Cancer Center ( Site 0010); 🇺🇸 Philadelphia, Pennsylvania, United States

MD Anderson Cancer Center ( Site 0065); 🇺🇸 Houston, Texas, United States

Texas Oncology-Denton South ( Site 8016); 🇺🇸 Denton, Texas, United States

Texas Oncology- Paris ( Site 8004); 🇺🇸 Paris, Texas, United States

CTRC at The University of Texas Health Science Center at San Antonio ( Site 0026); 🇺🇸 San Antonio, Texas, United States

Texas Oncology-Tyler ( Site 8005); 🇺🇸 Tyler, Texas, United States

Virginia Oncology Associates ( Site 8011); 🇺🇸 Norfolk, Virginia, United States

Texas Oncology-Waco ( Site 8012); 🇺🇸 Waco, Texas, United States

Providence Regional Cancer Partnership ( Site 0016); 🇺🇸 Everett, Washington, United States

Cancer Care Northwest ( Site 0021); 🇺🇸 Spokane, Washington, United States

Yakima Valley Memorial Hospital North Star Lodge ( Site 8017); 🇺🇸 Yakima, Washington, United States

Ballarat Health Services ( Site 0705); 🇦🇺 Ballarat, Australia

Instituto de Cancer e Transplante de Curitiba ICTR ( Site 1012); 🇧🇷 Curitiba, PR, Brazil

CancerCare Manitoba ( Site 0119); 🇨🇦 Winnipeg, Manitoba, Canada

Saskatoon Cancer Centre ( Site 0105); 🇨🇦 Saskatoon, Saskatchewan, Canada

Fundacion Arturo Lopez Perez FALP ( Site 0902); 🇨🇱 Santiago, Chile

Oncocentro ( Site 0900); 🇨🇱 Vina del Mar, Chile

Oncologos del Occidente S.A. ( Site 0800); 🇨🇴 Pereira, Risaralda, Colombia

Fundacion CardioInfantil Instituto de Cardiologia ( Site 0803); 🇨🇴 Bogota, Colombia

Oncomedica S.A. ( Site 0801); 🇨🇴 Monteria, Colombia

Nemocnice Novy Jicin a.s. Clen skupiny AGEL ( Site 1506); 🇨🇿 Novy Jicin, Czechia

Fakultni nemocnice Olomouc ( Site 1502); 🇨🇿 Olomouc, Czechia

Thomayerova nemocnice ( Site 1505); 🇨🇿 Praha 4, Czechia

HYKS ( Site 2300); 🇫🇮 Helsinki, Finland

ICO Centre Paul Papin ( Site 2208); 🇫🇷 Angers, France

CHU Besancon - Hopital Jean Minjoz ( Site 2200); 🇫🇷 Besancon, France

Hopital Europeen Georges Pompidou ( Site 2206); 🇫🇷 Paris, France

Hospices Civils de Lyon Centre Hospitalier Lyon Sud ( Site 2212); 🇫🇷 Pierre Benite, France

Campus Charite Mitte ( Site 2120); 🇩🇪 Berlin, Germany

Helios Klinikum Berlin Buch ( Site 2125); 🇩🇪 Berlin, Germany

Universitaetsklinikum Freiburg ( Site 2119); 🇩🇪 Freiburg, Germany

Universitaetsklinikum Frankfurt ( Site 2121); 🇩🇪 Frankfurt, Germany

Studienpraxis Urologie ( Site 2115); 🇩🇪 Nuertingen, Germany

Beaumont Hospital ( Site 1611); 🇮🇪 Dublin, Ireland

Istituto Nazionale Tumori Regina Elena ( Site 2009); 🇮🇹 Roma, Italy

Kindai University Hospital ( Site 0411); 🇯🇵 Osakasayama, Osaka, Japan

Japan Community Health care Organization Sendai Hospital ( Site 0430); 🇯🇵 Sendai, Miyagi, Japan

Osaka Rosai Hospital ( Site 0418); 🇯🇵 Sakai, Osaka, Japan

Kyushu University Hospital ( Site 0413); 🇯🇵 Fukuoka, Japan

Osaka International Cancer Institute ( Site 0401); 🇯🇵 Osaka, Japan

Keio University Hospital ( Site 0407); 🇯🇵 Tokyo, Japan

Toranomon Hospital ( Site 0426); 🇯🇵 Tokyo, Japan

Toyama University Hospital ( Site 0432); 🇯🇵 Toyama, Japan

Seoul National University Hospital ( Site 0302); 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center ( Site 0300); 🇰🇷 Seoul, Korea, Republic of

Centrum Onkologii Instytut im. Marii Skłodowskiej Curie ( Site 1323); 🇵🇱 Gliwice, Poland

Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu ( Site 1307); 🇵🇱 Bytom, Poland

Centrum Onkologii Instytut im. Marii Sklodowskiej Curie ( Site 1310); 🇵🇱 Krakow, Poland

Szpital Kliniczny Przemienienia Panskiego UM im. K. Marcinkowskiego ( Site 1311); 🇵🇱 Poznan, Poland

Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu ( Site 1305); 🇵🇱 Torun, Poland

Wojskowy Instytut Medyczny Centralny Szpital Medyczny MON ( Site 1300); 🇵🇱 Warszawa, Poland

N.N. Blokhin NMRCO ( Site 1206); 🇷🇺 Moscow, Russian Federation

Russian Scientific Center of Roentgenoradiology ( Site 1201); 🇷🇺 Moscow, Russian Federation

Bayandin Murmansk Regional Clinical Hospital ( Site 1214); 🇷🇺 Murmansk, Russian Federation

Hospital Universitario Infanta Cristina ( Site 1805); 🇪🇸 Badajoz, Spain

Clinical Hospital Bashkirsky Medical State University ( Site 1202); 🇷🇺 Ufa, Russian Federation

Hospital de Girona Dr. Josep Trueta ( Site 1806); 🇪🇸 Girona, Spain

Hospital de la Santa Creu i Sant Pau ( Site 1807); 🇪🇸 Barcelona, Spain

Hospital Universitario Gregorio Maranon ( Site 1801); 🇪🇸 Madrid, Spain

Clinica Universitaria de Navarra ( Site 1803); 🇪🇸 Pamplona, Spain

Hospital Universitario Virgen de la Victoria ( Site 1808); 🇪🇸 Malaga, Spain

Hospital Universitario Ramon y Cajal ( Site 1800); 🇪🇸 Madrid, Spain

Instituto Valenciano de Oncologia ( Site 1804); 🇪🇸 Valencia, Spain

Hospital Universitario y Politecnico La Fe de Valencia ( Site 1809); 🇪🇸 Valencia, Spain

Western General Hospital ( Site 1600); 🇬🇧 Edinburgh, United Kingdom

St George s Healthcare Trust ( Site 1608); 🇬🇧 London, United Kingdom

North Staffordshire Hospital in Stoke-on-Trent ( Site 1601); 🇬🇧 Stoke-On-Trent, Staffordshire, United Kingdom

The Christie NHS Foundation Trust ( Site 1602); 🇬🇧 Manchester, United Kingdom

The Beatson West of Scotland Cancer Centre ( Site 1605); 🇬🇧 Glasgow, United Kingdom

The James Cook University Hospital ( Site 1606); 🇬🇧 Middlesbrough, United Kingdom

Royal Free Hospital ( Site 1609); 🇬🇧 London, United Kingdom

Charing Cross Hospital ( Site 1607); 🇬🇧 London, United Kingdom

Georgetown University Medical Center ( Site 0002); 🇺🇸 Washington, District of Columbia, United States

Northwest Georgia Oncology Centers PC ( Site 0014); 🇺🇸 Marietta, Georgia, United States

Rutgers Cancer Institute of New Jersey ( Site 0059); 🇺🇸 New Brunswick, New Jersey, United States

UTHealth/Memorial Hermann Cancer Center ( Site 0001); 🇺🇸 Houston, Texas, United States

Texas Oncology-Memorial City ( Site 8015); 🇺🇸 Houston, Texas, United States

SCCA/UW ( Site 0029); 🇺🇸 Seattle, Washington, United States

Medical Oncology Associates (Summit Cancer Centers) ( Site 0005); 🇺🇸 Spokane, Washington, United States

Northwest Medical Specialties, PLLC ( Site 0034); 🇺🇸 Tacoma, Washington, United States

Instituto de Investigaciones Metabolicas -I.D.I.M.- ( Site 1113); 🇦🇷 Buenos Aires, Argentina

Saint George Hospital [Kogarah, Australia] ( Site 0707); 🇦🇺 Kogarah, New South Wales, Australia

Macquarie University Hospital ( Site 0700); 🇦🇺 Macquarie Park, New South Wales, Australia

Adelaide Cancer Centre ( Site 0703); 🇦🇺 Kurralta Park, South Australia, Australia

Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 1001); 🇧🇷 Porto Alegre, RS, Brazil

COT Centro Oncologico do Triangulo Ltda ( Site 1014); 🇧🇷 Uberlandia, Brazil

Hosp. Clinicas da Fac. de Medicina de Ribeirao Preto - USP ( Site 1016); 🇧🇷 Ribeirao Preto, Brazil

Niagara Health System - St. Catharines ( Site 0120); 🇨🇦 St. Catharines, Ontario, Canada

Health and Care Chile ( Site 0901); 🇨🇱 Santiago, Chile

Hospital Regional de La Serena ( Site 0907); 🇨🇱 La Serena, Chile

Sociedad de Investigaciones Medicas Limitadas ( Site 0913); 🇨🇱 Temuco, Chile

Hospital Pablo Tobon Uribe. ( Site 0805); 🇨🇴 Medellin, Antioquia, Colombia

Administradora Country SA - Clinica del Country ( Site 0808); 🇨🇴 Bogota, Colombia

FN Brno. ( Site 1501); 🇨🇿 Brno, Czechia

Fakultni nemocnice Ostrava ( Site 1507); 🇨🇿 Ostrava, Czechia

Fakultni nemocnice v Motole ( Site 1504); 🇨🇿 Praha 5, Czechia

Nemocnice Na Bulovce ( Site 1503); 🇨🇿 Praha 8, Czechia

Universitaetsklinikum der Technischen Universitaet Dresden ( Site 2113); 🇩🇪 Dresden, Germany

Universitaetsklinikum Schleswig Holstein ( Site 2109); 🇩🇪 Luebeck, Germany

Krankenhaus der Barmherzigen Brueder Trier ( Site 2117); 🇩🇪 Trier, Germany

Universitaetsklinikum Tuebingen ( Site 2100); 🇩🇪 Tuebingen, Germany

Ospedale San Luigi Gonzaga ( Site 2010); 🇮🇹 Orbassano, Torino, Italy

Akita University Hospital ( Site 0433); 🇯🇵 Akita, Japan

Nippon Medical School Hospital ( Site 0400); 🇯🇵 Tokyo, Japan

National Cancer Center ( Site 0304); 🇰🇷 Goyang-si, Gyeonggi-do, Korea, Republic of

Samsung Medical Center ( Site 0301); 🇰🇷 Seoul, Korea, Republic of

Mazowiecki Szpital Onkologiczny ( Site 1316); 🇵🇱 Wieliszew, Mazowieckie, Poland

Centrum Medyczne Onkologii I Hipertermii ( Site 1321); 🇵🇱 Warszawa, Poland

University Medical Center New Orleans ( Site 0053); 🇺🇸 New Orleans, Louisiana, United States

Charleston Hematology Oncology Associates PA ( Site 8000); 🇺🇸 Charleston, South Carolina, United States

Medical University of South Carolina ( Site 0033); 🇺🇸 Charleston, South Carolina, United States

Texas Oncology-Austin Central ( Site 8003); 🇺🇸 Austin, Texas, United States

University of Wisconsin Carbone Cancer Center ( Site 0019); 🇺🇸 Madison, Wisconsin, United States