Lenvatinib/Everolimus or Lenvatinib/Pembrolizumab Versus Sunitinib Alone as Treatment of Advanced Renal Cell Carcinoma

Phase 3

Active, not recruiting

• Conditions: Renal Cell Carcinoma
• Interventions: Drug: Lenvatinib; Drug: Sunitinib; Drug: Everolimus; Drug: Pembrolizumab

• Registration Number: NCT02811861
• Lead Sponsor: Eisai Inc.

Brief Summary

The primary purpose of the study is to demonstrate that lenvatinib in combination with everolimus (Arm A) or pembrolizumab (Arm B) is superior compared to sunitinib alone (Arm C) in improving progression-free survival (PFS) (by independent imaging review \[IIR\] using Response Evaluation Criteria in Solid Tumors \[RECIST 1.1\]) as first-line treatment in participants with advanced renal cell carcinoma (RCC).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-06-21
• Study First Submitted QC: 2016-06-21
• Study First Posted: 2016-06-23
• Study Start: 2016-10-13
• Primary Completion: 2020-08-28
• Results First Submitted: 2021-08-27
• Results First Submitted QC: 2021-08-27
• Results First Posted: 2021-09-24
• Status Verified: 2023-07
• Last Update Submitted: 2024-10-22
• Last Update Posted: 2024-11-01
• Study Completion: 2026-03-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 1069

Inclusion Criteria

1. Histological or cytological confirmation of RCC with a clear-cell component (original tissue diagnosis of RCC is acceptable).

2. Documented evidence of advanced RCC.

3. At least 1 measurable target lesion according to RECIST 1.1 meeting the following criteria:

   • Lymph node (LN) lesion that measures at least 1 dimension as greater than or equal to (>=) 1.5 cm in the short axis
   • Lymph node (LN) lesion that measures at least 1 dimension as greater than or equal to (>=) 1.5 centimeter (cm) in the short axis
   • Non-nodal lesion that measures greater than or equal to (>=) 1.0 cm in the longest diameter
   • The lesion is suitable for repeat measurement using computerized tomography/magnetic resonance imaging (CT/MRI). Lesions that have had external beam radiotherapy (EBRT) or locoregional therapy must show radiographic evidence of disease progression based on RECIST 1.1 to be deemed a target lesion.

3.Karnofsky Performance Status (KPS) of >=70 4.Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than or equal (<=) 150/90 millimeter of mercury (mmHg) at Screening and no change in antihypertensive medications within 1 week prior to Cycle 1/Day 1 (C1/D1) 5.Adequate renal function defined as creatinine <=1.5*upper limit of normal (ULN); or for participants with creatinine greater than (>) 1.5*ULN, the calculated creatinine clearance >=30 milliliters per minute (mL/min) (per the Cockcroft-Gault formula) is acceptable.

6.Adequate bone marrow function defined by:

• Absolute neutrophil count (ANC) >=1500/cubic millimeter (mm^3)

• Platelets >=100,000/mm^3

• Hemoglobin >=9 grams per deciliter (g/dL) NOTE: Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within the previous 2 weeks.

  7.Adequate blood coagulation function defined by International Normalized ratio (INR) <=1.5 unless participant is receiving anticoagulant therapy, as long as INR is within therapeutic range of intended use of anticoagulants.

  8.Adequate liver function defined by:

• Total bilirubin <=1.5*ULN except for unconjugated hyperbilirubinemia of Gilbert's syndrome.

• Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) <=3*ULN (in the case of liver metastases <=5*ULN), unless there are bone metastases. Participants with ALP values >3*ULN and known to have bone metastases can be included.

  9.Provide written informed consent. 10.Willing and able to comply with all aspects of the protocol.

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Exclusion Criteria

1. Participants who have received any systemic anticancer therapy for RCC, including anti-vascular endothelial growth factor (VEGF) therapy, or any systemic investigational anticancer agent. Prior adjuvant treatment with an investigational anticancer agent is not allowed unless the investigator can provide evidence of participant's randomization to placebo arm.

2. Participants with central nervous system (CNS) metastases are not eligible, unless they have completed local therapy (example, whole brain radiation therapy (WBRT), surgery or radiosurgery) and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (example, radiologic) or symptoms of CNS metastases must be stable for at least 4 weeks before starting study treatment

3. Active malignancy (except for RCC, definitively treated basal or squamous cell carcinoma of the skin, and carcinoma in-situ of the cervix or bladder) within the past 24 months. Participants with history of localized & low risk prostate cancer are allowed in the study if they were treated with curative intent and there is no prostate specific antigen (PSA) recurrence within the past 5 years

4. Prior radiation therapy within 21 days prior to start of study treatment with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks prior to study treatment start

5. Participants who are using other investigational agents or who had received investigational drugs <=4 weeks prior to study treatment start.

6. Received a live vaccine within 30 days of planned start of study treatment (Cycle 1/Day 1). Examples of live vaccines include, but are not limited to, measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (example, FluMist®) are live attenuated vaccines and are not allowed.

7. Participants with proteinuria >1+ on urine dipstick testing will undergo 24-h urine collection for quantitative assessment of proteinuria. Participants with urine protein >=1 g/24 h will be ineligible

8. Fasting total cholesterol >300 milligram per deciliter (mg/dL) (or ˃7.75 millimole per liter (mmol/L)) and/or fasting triglycerides level ˃2.5 x upper limit of normal (ULN). Note: these participants can be included after initiation or adjustment of lipid-lowering medication

9. Uncontrolled diabetes as defined by fasting glucose >1.5 times the ULN. Note: these participants can be included after initiation or adjustment of glucose-lowering medication

10. Prolongation of corrected QT (QTc) interval to >480 milliseconds (ms)

11. Participants who have not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy.

12. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib, everolimus, and/or sunitinib.

13. Bleeding or thrombotic disorders or participants at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy

14. Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug

15. Significant cardiovascular impairment within 12 months of the first dose of study drug: history of congestive heart failure greater than New York Heart Association Class II, unstable angina, myocardial infarction, cerebrovascular accident, or cardiac arrhythmia associated with hemodynamic instability. The following is also excluded: left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multiple-gated acquisition MUGA scan or echocardiogram

16. Active infection (any infection requiring systemic treatment)

17. Participants known to be positive for Human Immunodeficiency Virus (HIV).

18. Known active Hepatitis B (example, Hepatitis B surface antigen (HBsAg) reactive) or Hepatitis C (example, hepatitis C virus ribonucleic acid (HCV RNA) [qualitative] is detected)

19. Known history of, or any evidence of, interstitial lung disease

20. Has a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis

21. Participants with a diagnosis of immunodeficiency or who are receiving chronic systemic steroid therapy (doses exceeding 10 mg/day of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. Physiologic doses of corticosteroids (up to 10 mg/day of prednisone or equivalent) may be used during the study

22. Active autoimmune disease (with the exception of psoriasis) that has required systemic treatment in the past 2 years (that is, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (example, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.

23. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units of ß-hCG [or hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.

24. Females of childbearing potential who:

    • Do not agree to use a highly effective method of contraception for the entire study period and for 120 days after study discontinuation, that is:
    • total abstinence (if it is their preferred and usual lifestyle)
    • an intrauterine device (IUD) or hormone-releasing system (IUS)
    • a contraceptive implant
    • an oral contraceptive (with additional barrier method) OR
    • Do not have a vasectomized partner with confirmed azoospermia. For sites outside of the EU, it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the participant, then the participant must agree to use a medically acceptable method of contraception, that is, double barrier methods of contraception such as condom plus diaphragm or cervical/vault cap with spermicide.

25. Males who have not had a successful vasectomy (confirmed azoospermia) and do not agree to use condom + spermicide OR have a female partner who does not meet the criteria above (that is, is of childbearing potential and not practicing highly effective contraception throughout the study period), starting with the first dose of study therapy through 120 days after the last dose of study therapy, unless sexually abstinent. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.

26. Known intolerance to any of the study drugs (or any of the excipients)

27. Participant has had an allogenic tissue/solid organ transplant.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lenvatinib 18 mg plus Everolimus 5 mg	Lenvatinib	Lenvatinib 18 milligrams (mg) administered orally, once daily, plus everolimus 5 mg administered orally, once daily in each 21-day cycle.
Sunitinib 50 mg	Sunitinib	Sunitinib 50 mg administered orally, once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment in each 21-day cycle.
Lenvatinib 20 mg plus Pembrolizumab 200 mg	Lenvatinib	Lenvatinib 20 mg administered orally, once daily, in each 21-day cycle plus pembrolizumab 200 mg administered intravenously (IV), every 3 weeks on Day 1 of each 21-day cycle.
Lenvatinib 18 mg plus Everolimus 5 mg	Everolimus	Lenvatinib 18 milligrams (mg) administered orally, once daily, plus everolimus 5 mg administered orally, once daily in each 21-day cycle.
Lenvatinib 20 mg plus Pembrolizumab 200 mg	Pembrolizumab	Lenvatinib 20 mg administered orally, once daily, in each 21-day cycle plus pembrolizumab 200 mg administered intravenously (IV), every 3 weeks on Day 1 of each 21-day cycle.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS) by Independent Imaging Review (IIR)	From the date of randomization to the date of the first documentation of PD or date of death, whichever occurred first or up to data cutoff date 28 Aug 2020 (up to approximately 46 months)	PFS assessed by IIR was defined as the time from the date of randomization to the date of the first documentation of progressive disease (PD) or death (whichever occurred first) using Response Evaluation Criteria in Solid Tumors (RECIST 1.1). PD was defined as at least a 20 percent (%) increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS was analyzed using Kaplan-Meier method.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Up to approximately 69 months	OS is defined as the time from the date of randomization to the date of death from any cause. Participants who were lost to follow-up and those who were alive at the data cutoff date were censored, either at the last date the participant was last known alive or at the data cutoff date, whichever occurred first. Data for this outcome measure will be reported after study completion (anticipated study completion date is July 2024).
Time to Treatment Failure Due to Toxicity	Up to approximately 69 months	Time to treatment failure due to toxicity is defined as time from the date of randomization to the date that a participant discontinued study treatment due to TEAEs. Data for this outcome measure will be reported after study completion (anticipated study completion date is July 2024).
HRQoL Assessed by European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Score	Up to approximately 69 months	EORTC QLQ-C30 is a questionnaire including 30 questions that rate the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores are transformed to a range of 0 to 100 using a standard EORTC algorithm. For the overall HRQoL and functioning scales, a higher score is correlated with better HRQoL, whereas a higher score represents worse HRQoL for symptom scales. Data for this outcome measure will be reported after study completion (anticipated study completion date is July 2024).
PFS on Next-line of Therapy (PFS2)	Up to approximately 69 months	PFS2 is defined as the time from randomization to disease progression as assessed by investigator on next-line treatment or death from any cause (whichever occurred first). Data for this outcome measure will be reported after study completion (anticipated study completion date is July 2024).
Number of Participants Who Discontinued Treatment Due to Toxicity	Up to approximately 69 months	Data for this outcome measure will be reported after study completion (anticipated study completion date is July 2024).
Objective Response Rate (ORR)	Up to approximately 69 months	ORR is defined as the proportion of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) as determined by IIR using RECIST 1.1. CR is defined as disappearance of all (targeted and non-target \[NT\]) lesions. All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (\<) 10mm. PR: defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. To be considered a BOR, all responses had to be confirmed no less than 4 weeks after the initial assessment of response. Data for this outcome measure will be reported after study completion (anticipated study completion date is July 2024).
Number of Participants With At Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Up to approximately 69 months	TEAEs were defined as those adverse events (AEs) that occurred (or worsened, if present at Baseline) after the first dose of study drug through 30 days after the last dose of study drug.An AE was defined as any untoward medical occurrence in a participants or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. A SAE was defined as any AE if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect. Data for this outcome measure will be reported after study completion (anticipated study completion date is July 2024).
Health-Related Quality of Life (HRQoL) Assessed by Functional Assessment of Cancer Therapy Kidney Syndrome Index-Disease-Related Symptoms (FKSI-DRS) Scores	Up to approximately 69 months	The FKSI-DRS consisted of 9 items that experts and participants had indicated are important targets for the treatment of advanced kidney cancer, and that clinical experts had indicated are primarily disease-related, as opposed to treatment-related. Symptoms assessed on the FKSI-DRS included lack of energy, fatigue, weight loss, pain, bone pain, shortness of breath, cough, fever, or hematuria. Each item was scored on a 5-point Likert-type scale (0 = not at all; 4 = very much) where total score ranged from 0 (worst) to 36 (best), where higher scores correspond to better outcomes. Data for this outcome measure will be reported after study completion (anticipated study completion date is July 2024).
PFS by Investigator Assessment	Up to approximately 69 months	PFS by investigator assessment is defined as the time from the date of randomization to the date of first documentation of disease progression based on the investigator assessment per RECIST 1.1 or death (whichever occurred first). Data for this outcome measure will be reported after study completion (anticipated study completion date is July 2024).
Model-predicted Clearance for Lenvatinib and Everolimus	Cycles 1 and 2 Day 1; 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 15: predose and 2-12 hours postdose; Cycles 3, 4, 5 and 6 Day 1: predose (Cycle length=21 days)	Data for this outcome measure will be reported after study completion (anticipated study completion date is July 2024).
HRQoL Assessed by European Quality of Life (EuroQol) Five-Dimensional, 3-Level (EQ-5D-3L) Score	Up to approximately 69 months	EQ-5D-3L is a health profile questionnaire consisting of the EQ-5D descriptive system and the EuroQol visual analog scale (EQ-VAS). For the EQ-5D, participants rate 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) at 1 of 3 levels (1=no problems; 2=some problems; 3=extreme problems). The EQ-5D Health Utilities Index (HUI) is derived from the five dimensions of the EQ-5D, using country-specific preference weights (tariffs) to summarize how good or bad each health state is on a scale from 1 (full health) to \<0 (worse health/dead). The EQ-VAS measures self-rated global health status using a vertically oriented VAS, where 100 represents the "best imaginable health state" and 0 represents the "worst imaginable health state." Data for this outcome measure will be reported after study completion (anticipated study completion date is July 2024).
Area Under the Plasma Drug Concentration-time Curve (AUC) for Lenvatinib and Everolimus	Cycles 1 and 2 Day 1; 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 15: predose and 2-12 hours postdose; Cycles 3, 4, 5 and 6 Day 1: predose (Cycle length = 21 days	Data for this outcome measure will be reported after study completion (anticipated study completion date is July 2024).

Trial Locations

Locations (162)

Chaim Sheba Medical Center; 🇮🇱 Ramat-Gan, Israel

Facility #2; 🇯🇵 Tokyo, Japan

Mount Sinai Medical Center; 🇺🇸 Miami Beach, Florida, United States

Hackensack Medical Center; 🇺🇸 Hackensack, New Jersey, United States

Institut Jules Bordet; 🇧🇪 Bruxelles, Belgium

O.L.V Ziekenhuis; 🇧🇪 Aalst, Belgium

FSBI "Moscow scientific research oncology institute n.a. P.A. Gertsen" of MoH of RF; 🇷🇺 Moscow, Russian Federation

BHI of Omsk region "Clinical Oncology Dispensary"; 🇷🇺 Omsk, Russian Federation

Hospital Universitario Marques de Valdecilla; 🇪🇸 Santander, Cantabria, Spain

FSBI "National Medical Research Radiological Center" of the MoH of the RF; 🇷🇺 Obninsk, Russian Federation

Hospital Universitario Virgen del Rocio; 🇪🇸 Seville, Spain

Hospital Universitario Central de Asturias; 🇪🇸 Oviedo, Spain

Royal Bournemouth General Hospital; 🇬🇧 Bournemouth, United Kingdom

FSBSI Russian Oncological Scientific Center n.a. N.N. Blokhin - Department of Oncology; 🇷🇺 Moscow, Russian Federation

SPWSZ w Szczecinie im. Marii Sklodowskiej-Curie; 🇵🇱 Szczecin, Poland

ICO l'Hospitalet - Hospital Duran I Reynals; 🇪🇸 Barcelona, Spain

SBHI of Novosibirsk region "Novosibirsk Regional Oncological Dispensary"; 🇷🇺 Novosibirsk, Russian Federation

Western General Hospital; 🇬🇧 Edinburgh, United Kingdom

Hospital Universitario Ramon y Cajal; 🇪🇸 Madrid, Spain

Hospital Universitario Clinico San Carlos; 🇪🇸 Madrid, Spain

Hospital Clinic i Provincial de Barcelona; 🇪🇸 Barcelona, Spain

Christie Hospital NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom

FBHI Privolzhskiy District Medical Centre FMBA of Russia; 🇷🇺 Nizhniy Novgorod, Russian Federation

Hospital Universitario HM Madrid Sanchinarro; 🇪🇸 Madrid, Spain

Inselspital - Universitaetsspital Bern; 🇨🇭 Bern, Switzerland

Velindre Cancer Centre; 🇬🇧 Cardiff, United Kingdom

Beatson West Of Scotland Cancer Centre; 🇬🇧 Glasgow, United Kingdom

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

St. James's University Hospital; 🇬🇧 Leeds, United Kingdom

MD Anderson Cancer Centre; 🇪🇸 Madrid, Spain

Oncologia; 🇪🇸 Valencia, Spain

Hospital General Universitario Gregorio Maranon; 🇪🇸 Madrid, Spain

Hospital San Pedro de Alcantara; 🇪🇸 Caceres, Spain

Hospital Universitario Reina Sofia; 🇪🇸 Cordoba, Spain

Royal Free Hospital; 🇬🇧 London, United Kingdom

Rosewell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States

Medizinische Universitat Innsbruck; 🇦🇹 Innsbruck, Austria

Ottawa Hospital Cancer Centre; 🇨🇦 Ottawa, Ontario, Canada

London Institute of Health Sciences; 🇨🇦 London, Ontario, Canada

EISAI Trial site 6; 🇩🇪 Frankfurt, Hessen, Germany

Health Midwest Ventures Group, Inc d/b/a HCA MidAmerica Division, LLC; 🇺🇸 Overland Park, Kansas, United States

Cotton-Oneil Clinical Research Center; 🇺🇸 Topeka, Kansas, United States

EISAI Trial site 13; 🇩🇪 Münster, Nordrhein Westfalen, Germany

EISAI Trial site 14; 🇩🇪 Greifswald, Mecklenburg-Vorpommern, Germany

Adelaide and Meath Hospital Incorp The National Children's Hospital; 🇮🇪 Dublin, Ireland

Uniwersyteckie Centrum Kliniczne; 🇵🇱 Gdansk, Poland

A.O.U. Policlinico di Modena; 🇮🇹 Modena, Italy

University of Miami; 🇺🇸 Miami, Florida, United States

GU Research Network; 🇺🇸 Omaha, Nebraska, United States

Nebraska Cancer Specialists; 🇺🇸 Omaha, Nebraska, United States

SCRI - Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

I.R.C.S.S Fondazione Maugeri; 🇮🇹 Pavia, Italy

Boca Raton Community Hospital; 🇺🇸 Boca Raton, Florida, United States

Stanford School of Medicine; 🇺🇸 Stanford, California, United States

Florida Cancer Specialists; 🇺🇸 West Palm Beach, Florida, United States

Florida Cancer Specialists ( North Region); 🇺🇸 Saint Petersburg, Florida, United States

Joliet Oncology - Hematology Associates; 🇺🇸 Joliet, Illinois, United States

Healthcare Research Network III, LLC; 🇺🇸 Tinley Park, Illinois, United States

Karmanos Cancer Center; 🇺🇸 Detroit, Michigan, United States

Massachusetts General Hospital- MGH; 🇺🇸 Boston, Massachusetts, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Broome Oncology; 🇺🇸 Johnson City, New York, United States

Weill Cornell Medical College New York Presbyterian Hospital; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Mission Hospital_ Cancer Care of Western North Carolina; 🇺🇸 Asheville, North Carolina, United States

Oncology Hematology Care; 🇺🇸 Cincinnati, Ohio, United States

Texas Oncology, P.A.; 🇺🇸 Dallas, Texas, United States

Texas Oncology PA; 🇺🇸 Fort Worth, Texas, United States

Texas Oncology PA - McAllen; 🇺🇸 McAllen, Texas, United States

USOR Texas Oncology; 🇺🇸 The Woodlands, Texas, United States

Texas Oncology PA - Paris; 🇺🇸 Paris, Texas, United States

Texas Oncology PA - Tyler; 🇺🇸 Tyler, Texas, United States

Austin Health; 🇦🇺 Heidelberg, Victoria, Australia

Box Hill Hospital; 🇦🇺 Box Hill, Victoria, Australia

Royal Hobart Hospital; 🇦🇺 Hobart, Australia

Macquarie University Hospital; 🇦🇺 Macquarie park, Australia

ICON Cancer Foundation; 🇦🇺 South Brisbane, Australia

Sunshine Hospital; 🇦🇺 St Albans, Australia

Krankenhaus der barmherzigen Schwestern Linz; 🇦🇹 Linz, Austria

AKH - Medizinische Universität Wien; 🇦🇹 Vienna, Austria

ZNA Middelheim; 🇧🇪 Antwerpen, Belgium

Imeldaziekenhuis; 🇧🇪 Bonheiden, Belgium

Domaine Universitaire; 🇧🇪 Liege, Belgium

Jessa Ziekenhuis - Campus Virga Jesse; 🇧🇪 Hasselt, Belgium

GZA Ziekenhuizen - Campus Sint-Augustinus; 🇧🇪 Wilrijk, Belgium

Cross Cancer Institute; 🇨🇦 Edmonton, Alberta, Canada

BC Cancer Agency Vancouver Centre; 🇨🇦 Vancouver, British Columbia, Canada

Sunnybrook Research Institute - University of Toronto; 🇨🇦 Toronto, Ontario, Canada

Centre de santé et de services sociaux Champlain-Charles-Le Moyne; 🇨🇦 Greenfield Park, Quebec, Canada

Fakultni nemocnice u sv. Anny v Brne; 🇨🇿 Brno, Czechia

Masarykuv onkologicky ustav; 🇨🇿 Brno, Czechia

Fakultni nemocnice Olomouc, Neurologicka klinika; 🇨🇿 Olomouc, Czechia

Fakultni nemocnice v Motole; 🇨🇿 Praha 5, Czechia

Thomayerova nemocnice; 🇨🇿 Praha 4, Czechia

ICO - Site Paul Papin; 🇫🇷 Angers, Maine Et Loire, France

Centre Georges François Leclerc; 🇫🇷 Dijon cedex, France

Nemocnice Na Bulovce; 🇨🇿 Praha 8, Czechia

Clinique Victor Hugo - Centre Jean Bernard; 🇫🇷 Le Mans Cedex, France

Institut Regional du Cancer de Montpellier; 🇫🇷 Montpellier, France

CHU Strasbourg - Nouvel Hopital Civil; 🇫🇷 Strasbourg, France

Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes; 🇫🇷 Lyon, France

Hopital la Petie Salpetriere; 🇫🇷 Paris, France

Boulevard du Professeur Jacques Monod; 🇫🇷 Saint Herblain, France

Hopital Europeen Georges Pompidou; 🇫🇷 Paris, France

EISAI Trial site 4; 🇩🇪 Stuttgart, Baden Wuerttemberg, Germany

EISAI Trial site 1; 🇩🇪 Tuebingen, Baden Wuerttemberg, Germany

EISAI Trial site 7; 🇩🇪 München, Bayern, Germany

EISAI Trial site 8; 🇩🇪 Hannover, Niedersachsen, Germany

EISAI Trial site 5; 🇩🇪 Berlin, Germany

EISAI Trial site 2; 🇩🇪 Homburg/Saar, Saarland, Germany

General Hospital of Athens "Alexandra"; 🇬🇷 Athens, Greece

University of Patras Medical School; 🇬🇷 Patras, Greece

General Hospital Papageorgiou; 🇬🇷 Thessaloníki, Greece

Interbalkan Hospital of Thessaloniki; 🇬🇷 Thessaloníki, Greece

Cork University Hospital,Wilton; 🇮🇪 Cork, Ireland

Beaumont Hospital; 🇮🇪 Dublin, Ireland

University Hospital Galway; 🇮🇪 Galway, Ireland

Assaf Harofeh Medical Center; 🇮🇱 Be'er Ya'aqov, Israel

Rambam MC; 🇮🇱 Haifa, Israel

Sapir Medical Center, Meir Hospital; 🇮🇱 Kfar-Saba, Israel

Rabin Medical Center-Beilinson Campus; 🇮🇱 Petah Tikva, Israel

Azienda Unità Sanitaria Locale- Ravenna; 🇮🇹 Faenza, Ravenna, Italy

Tel Aviv Sourasky Medical Center; 🇮🇱 Tel Aviv, Israel

Ospedale San Donato; 🇮🇹 Arezzo, Italy

Azienda Ospedaliera Universitaria Policlinico SantOrsola Malpighi; 🇮🇹 Bologna, Italy

Istituto Nazionale per la Ricerca sul Cancro di Genova; 🇮🇹 Genova, Italy

Azienda Ospedaliera di Rilievo Nazionale A. Cardarelli; 🇮🇹 Napoli, Italy

Presidio Ospedaliero Vito Fazzi; 🇮🇹 Lecce, Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST; 🇮🇹 Meldola, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori; 🇮🇹 Milano, Italy

Istituto Nazionale Tumori Fondazione G. Pascale; 🇮🇹 Napoli, Italy

Fondazione IRCCS Policlinico San Matteo; 🇮🇹 Pavia, Italy

Azienda Ospedaliera Santa Maria Degli Angeli; 🇮🇹 Pordenone, Italy

Azienda Ospedaliera San Camillo Forlanini; 🇮🇹 Roma, Italy

Universita Campus Bio-Medico di Roma; 🇮🇹 Rome, Italy

Facility #4; 🇯🇵 Tokyo, Japan

Facility #3; 🇯🇵 Tokyo, Japan

Facility #1; 🇯🇵 Tokyo, Japan

Facility #6; 🇯🇵 Tokyo, Japan

Facility #5; 🇯🇵 Tokyo, Japan

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

National Cancer Center; 🇰🇷 Goyang-si, Korea, Republic of

Kyungpook National University Chilgok Hospital; 🇰🇷 Daegu, Korea, Republic of

Asan Medical Center: Medical Oncology Department; 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center: Urology Department; 🇰🇷 Seoul, Korea, Republic of

Department of Internal Medicine Division of Hematology/Oncology Cancer center 11F; 🇰🇷 Seoul, Korea, Republic of

Antoni van Leeuwenhoek; 🇳🇱 Amsterdam, Netherlands

The Catholic University of Korea, Seoul St. Mary's Hospital; 🇰🇷 Seoul, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Severance Hospital, Yonsei University Health System; 🇰🇷 Seoul, Korea, Republic of

VU Medisch Centrum; 🇳🇱 Amsterdam, Netherlands

Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie; 🇵🇱 Lublin, Poland

Associates in Oncology & Hematology, PC; 🇺🇸 Bethesda, Maryland, United States

Florida Hospital Cancer Institute; 🇺🇸 Orlando, Florida, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Ochsner Clinic Foundation; 🇺🇸 New Orleans, Louisiana, United States

UMC Utrecht; 🇳🇱 Utrecht, Netherlands

FSBSI Russian Oncological Scientific Center n.a. N.N. Blokhin - Department of Urology; 🇷🇺 Moscow, Russian Federation

Guy's Hospital; 🇬🇧 London, United Kingdom

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States

St. Joseph's Healthcare Hamilton; 🇨🇦 Hamilton, Ontario, Canada