Study of First-line Pembrolizumab (MK-3475) With Lenvatinib (MK-7902/E7080) in Urothelial Carcinoma Cisplatin-ineligible Participants Whose Tumors Express Programmed Cell Death-Ligand 1 and in Participants Ineligible for Platinum-containing Chemotherapy (MK-7902-011/E7080-G000-317/ LEAP-011)
- Conditions
- Urothelial Carcinoma
- Interventions
- Registration Number
- NCT03898180
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to evaluate the efficacy and safety of lenvatinib (MK-7902/E7080) in combination with pembrolizumab (MK-3475) in the treatment of cisplatin-ineligible participants with a Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10, or in participants ineligible for any platinum-containing chemotherapy regardless of CPS, with advanced/unresectable or metastatic urothelial carcinoma (UC).
The primary hypotheses for this study are that:
1. Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR), and
2. Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Overall Survival (OS).
Based on recommendation of the external Data Monitoring Committee (eDMC), Amendment 3 (effective: September \[Sep\]-24-2021) was implemented to unblind the study and discontinue lenvatinib and placebo treatment. The eDMC was then disbanded.
With Amendment 4 (effective: December-5-2022) second course pembrolizumab will no longer be offered. Any participant receiving second course pembrolizumab treatment prior to initiation of Amendment 4 will be able to complete treatment as planned. Study participation will end after the final administration of pembrolizumab. Participants who either complete 35 administrations of pembrolizumab or discontinue pembrolizumab will discontinue from the study following the safety follow-up visit. AEs and spontaneously reported pregnancies will be reported and followed per protocol. The overall study ends when the last participant completes the last study-related contact or visit, withdraws from the study, or is lost to follow-up.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 505
- Has a histologically or cytologically confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial carcinoma (UC) of the renal pelvis, ureter (upper urinary tract), bladder, or urethra.
- Has ≥1 measurable target lesion per RECIST 1.1 as assessed by the local site investigator/radiologist.
- Has provided an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated and adequate for Programmed Death-Ligand 1 (PD-L1) evaluation.
- Has received no prior systemic chemotherapy for advanced or metastatic UC with the following exceptions:
- Neoadjuvant (prior to surgery) platinum-based chemotherapy for treatment of muscle-invasive bladder cancer with recurrence >12 months from completion of the therapy is permitted.
- Adjuvant (following surgery) platinum-based chemotherapy following radical cystectomy, with recurrence >12 months from completion of the therapy, is permitted.
- Meets criteria for either option a or option b (below):
- a. Has a tumor(s) with PD-L1 combined positive score (CPS) ≥10 and is considered ineligible to receive cisplatin-based combination therapy, based on 1 of the following:
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 2 within 7 days prior to randomization
- National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade ≥2 audiometric hearing loss
- NCI CTCAE Version 4.0 Grade ≥2 peripheral neuropathy OR
- b. In the opinion of the investigator, is considered ineligible to receive any platinum-based chemotherapy (i.e., ineligible for cisplatin and carboplatin) based on:
- ECOG PS of 2 within 7 days prior to randomization and ≥1 of the following:
- Documented visceral metastatic disease
- NCI CTCAE Version 4.0 Grade ≥2 audiometric hearing loss
- NCI CTCAE Version 4.0 Grade ≥2 peripheral neuropathy
- Other reason for the participant's being unable to receive both cisplatin and carboplatin safely. Additional criteria for platinum ineligibility will be considered and allowed on a case-by-case basis, following consultation with the Sponsor. Note: Participants considered ineligible for any platinum-based chemotherapy are eligible for this study regardless of their tumor PD-L1 status.
- Has ECOG PS 0, 1, or 2 within 7 days prior to randomization and a life expectancy of ≥3 months.
- Male participants are eligible to participate if they agree to the following during the treatment period and for ≥30 days after the last dose of pembrolizumab or lenvatinib/placebo:
- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR
- Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause as detailed below:
- Agrees to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
- A female participant is eligible to participate if she is not pregnant or breastfeeding and if she is not a WOCBP OR is a WOCBP and is using a contraceptive method that is highly effective (with a failure rate of <1% per year) with low user dependency, or is abstinent from heterosexual intercourse as her preferred and usual lifestyle during the intervention period and for ≥120 days post pembrolizumab or ≥30 days post lenvatinib/placebo.
- Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg at screening and no change in antihypertensive medications within 1 week prior to randomization.
- Has adequate organ function.
- Has disease that is suitable for local therapy administered with curative intent (e.g. chemotherapy and radiation for Stage 3 disease).
- Has tumor with any neuroendocrine or small cell component.
- Has a history of a gastrointestinal condition or procedure (e.g. gastric bypass, malabsorption) that, in the opinion of the investigator, may affect oral drug absorption.
- Has had major surgery within 3 weeks prior to the first dose of study treatment
- Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula.
- Has radiographic evidence of major blood vessel invasion/infiltration, or has had clinically significant hemoptysis (≥0.5 teaspoon of bright red blood) or tumor bleeding within 2 weeks prior to the first dose of study treatment.
- Has had significant cardiovascular impairment within 12 months of the first dose of study treatment, such as history of New York Heart Association (NYHA) >Class II congestive heart failure, unstable angina, myocardial infarction or cerebrovascular accident (CVA)/stroke, cardiac revascularization procedure, or cardiac arrhythmia associated with hemodynamic instability.
- Has known intolerance or severe hypersensitivity (Grade ≥3) to pembrolizumab or lenvatinib or any of their excipients
- Has received lenvatinib as monotherapy or in combination with a programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitor or has previously been enrolled in a clinical study evaluating lenvatinib for bladder cancer, regardless of the treatment received.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 inhibitor, indoleamine-pyrrole 2,3 dioxygenase (IDO1) inhibitor, or agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4], OX 40, CD137), or any other antibody or drug targeting T-cell costimulatory pathways in the adjuvant or advanced/metastatic setting.
- Has received prior radiotherapy to a metastatic site without the use of chemotherapy radiosensitization within 3 weeks of the first dose of study treatment, with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks before the start of study treatment. Participants must have recovered from all radiation-related toxicities, and must not require corticosteroids.
- Has received a live vaccine within 30 days prior to the first dose of study treatment.
- In the investigator's judgment, has not recovered from toxicity or other complications from any major surgery prior to starting 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. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
- Has history or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (at a dose exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization.
- Has had an active malignancy (except locally advanced or metastatic UC) within the past 36 months. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) who have undergone potentially curative therapy are not excluded.
- Has a history of prostate cancer (T2NXMX or lower with Gleason score ≤7) treated with definitive intent (surgically or with radiation therapy) ≥1 year prior to study entry is acceptable, provided that the participant is considered prostate cancer-free.
- Has central nervous system (CNS) metastases, unless the participant has completed local therapy (e.g. whole brain radiation therapy, surgery, or radiosurgery) and has discontinued use of corticosteroids for this indication for ≥4 weeks before starting study treatment. Any signs (e.g. radiologic) or symptoms of CNS metastases must be stable for ≥4 weeks before starting study treatment.
- Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with disease-modifying agents, corticosteroids, or immunosuppressive drugs).
- Has a history of (non-infectious) pneumonitis that required systemic steroids, or current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a known history of human immunodeficiency virus (HIV) infection.
- Has a known history of or is positive for active hepatitis B virus (HBV) or has active hepatitis C virus (HCV).
- Has active tuberculosis (TB).
- Is receiving hemodialysis.
- 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 pembrolizumab and lenvatinib/placebo.
- Has had an allogeneic tissue/solid organ transplant.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pembrolizumab + Lenvatinib Pembrolizumab Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to \~2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) until progressive disease or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinue lenvatinib. Pembrolizumab + Lenvatinib Lenvatinib Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to \~2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) until progressive disease or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinue lenvatinib. Pembrolizumab + Placebo Pembrolizumab Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to \~2 years) PLUS placebo for lenvatinib via oral capsule QD until progressive disease or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinue placebo. Pembrolizumab + Placebo Placebo for lenvatinib Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to \~2 years) PLUS placebo for lenvatinib via oral capsule QD until progressive disease or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinue placebo.
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) Up to approximately 25 months PFS was defined as the time from randomization to the first documented PD per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR), or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS as assessed by BICR per RECIST 1.1 is presented. Protocol-specified final analysis for this primary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.
Overall Survival (OS) Up to approximately 25 months OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. Protocol-specified final analysis for this primary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) Up to approximately 25 months ORR was defined as the percentage of participants who had a confirmed CR (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by BICR. The percentage of participants who experienced a CR or PR is presented. Protocol-specified final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.
Disease Control Rate (DCR) Up to approximately 25 months DCR was defined as the percentage of participants who have a CR (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD \[PD: ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD\]). DCR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. The DCR as assessed by BICR per RECIST 1.1 is presented. Protocol-specified final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.
Duration of Response (DOR) Up to approximately 25 months For participants who demonstrated a confirmed CR (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by BICR, DOR was defined as the time from first documented evidence of a CR or PR until PD or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions as well as an absolute increase of ≥5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. The DOR as assessed by BICR per RECIST 1.1 for participants who experienced a confirmed CR or PR is presented. Protocol-specified final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS) (Item 29) and Quality of Life (QOL) (Item 30) Combined Score Baseline and Week 11 The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions regarding GHS ("How would you rate your overall health during the past week?") and QOL ("How would you rate your overall quality of life during the past week?") were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QOL (EORTC QLQ-C30 Item 30) combined score is presented. A higher score indicates a better outcome. Final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021, as specified in the Supplemental Statistical Analysis Plan (sSAP).
Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 GHS (Item 29) and QOL (Item 30) Combined Score Baseline and up to approximately 25 months TTD was defined as the time from baseline to the first onset of a ≥10-point negative change (decrease) from baseline in GHS (EORTC QLQ-C30 Item 29) \& QOL (EORTC QLQ-C30 Item 30) combined score. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions regarding GHS ("How would you rate your overall health during the past week?") and QOL ("How would you rate your overall quality of life during the past week?") were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in GHS and QOL combined score, is presented. A longer TTD indicates a better outcome. Final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021, as specified in the sSAP.
Number of Participants Who Experience an AE Up to approximately 25 months An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE is presented. Final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.
Number of Participants Who Discontinue Study Treatment Due to an AE Up to approximately 25 months An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued study treatment due to an AE is presented. Final analysis for this secondary outcome measure was performed with an analysis data cut-off date of Jul-26-2021.
Trial Locations
- Locations (194)
Seattle Cancer Care Alliance ( Site 0003)
🇺🇸Seattle, Washington, United States
Northwest Georgia Oncology Centers PC ( Site 0707)
🇺🇸Marietta, Georgia, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0002)
🇺🇸New York, New York, United States
National Taiwan University Hospital ( Site 0211)
🇨🇳Taipei, Taiwan
Banner MD Anderson Cancer Center ( Site 0016)
🇺🇸Gilbert, Arizona, United States
Joliet Oncology Hematology ( Site 0091)
🇺🇸Joliet, Illinois, United States
John Wayne Cancer Institute ( Site 0017)
🇺🇸Santa Monica, California, United States
University of Chicago ( Site 0039)
🇺🇸Chicago, Illinois, United States
University of California Irvine Medical Center ( Site 0078)
🇺🇸Orange, California, United States
St. Peter's Hospital Cancer Care Center ( Site 0042)
🇺🇸Albany, New York, United States
Community Cancer Institute ( Site 0777)
🇺🇸Clovis, California, United States
Mercy Hospital Saint Louis - David C. Pratt Cancer Center ( Site 0095)
🇺🇸Saint Louis, Missouri, United States
Amphia Ziekenhuis Breda ( Site 0331)
🇳🇱Breda, Noord-Brabant, Netherlands
Haga Ziekenhuis ( Site 0333)
🇳🇱Den Haag, Zuid-Holland, Netherlands
Erasmus MC ( Site 0332)
🇳🇱Rotterdam, Zuid-Holland, Netherlands
St. Antonius Ziekenhuis ( Site 0335)
🇳🇱Utrecht, Netherlands
CEMAIC ( Site 0581)
🇦🇷Cordoba, Argentina
Instituto Medico Alexander Fleming ( Site 0578)
🇦🇷Buenos Aires, Caba, Argentina
Instituto de Investigaciones Metabolicas ( Site 0589)
🇦🇷Buenos Aires, Argentina
Centro Medico Dra De Salvo ( Site 0593)
🇦🇷Buenos Aires, Argentina
Baylor Scott & White Medical Center - Temple ( Site 0706)
🇺🇸Temple, Texas, United States
Thomas Jefferson University Hospital ( Site 0051)
🇺🇸Philadelphia, Pennsylvania, United States
Bajcsy Zsilinszki Korhaz es Rendelointezet ( Site 0509)
🇭🇺Budapest, Hungary
Markusovszky Egyetemi Oktatokorhaz ( Site 0502)
🇭🇺Szombathely, Vas, Hungary
Sunnybrook Research Institute ( Site 0106)
🇨🇦Toronto, Ontario, Canada
Austin Health-Austin Hospital ( Site 0154)
🇦🇺Heidelberg, Victoria, Australia
Hopital de la Timone ( Site 0246)
🇫🇷Marseille, Bouches-du-Rhone, France
Centre Hospitalier de la Cote Basque ( Site 0239)
🇫🇷Bayonne, Pyrenees-Atlantiques, France
Azienda Ospedaliera Santa Maria ( Site 0303)
🇮🇹Terni, Italy
Macquarie University ( Site 0151)
🇦🇺North Ryde, New South Wales, Australia
Assaf Harofeh Medical Center ( Site 0556)
🇮🇱Zerifin, Israel
Uzsoki Utcai Korhaz ( Site 0508)
🇭🇺Budapest, Hungary
Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 0504)
🇭🇺Kaposvar, Hungary
CHU de Bordeaux- Hopital Saint Andre ( Site 0235)
🇫🇷Bordeaux, Gironde, France
University of Tsukuba Hospital ( Site 0126)
🇯🇵Tsukuba, Ibaraki, Japan
Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 0507)
🇭🇺Szolnok, Jasz-Nagykun-Szolnok, Hungary
Peninsula Health Frankston Hospital ( Site 0153)
🇦🇺Frankston, Victoria, Australia
CHU Poitiers ( Site 0253)
🇫🇷Poitiers, Ain, France
CHUQ-Univ Laval-Hotel Dieu de Quebec ( Site 0104)
🇨🇦Quebec, Canada
Universitaetsmedizin Goettingen ( Site 0281)
🇩🇪Gottingen, Niedersachsen, Germany
CHIC Quimper ( Site 0245)
🇫🇷Quimper, Finistere, France
Meir Medical Center ( Site 0554)
🇮🇱Kfar Saba, Israel
Sourasky Medical Center ( Site 0561)
🇮🇱Tel Aviv, Israel
Sheba Medical Center ( Site 0551)
🇮🇱Ramat Gan, Israel
Lakeridge Health ( Site 0103)
🇨🇦Oshawa, Ontario, Canada
CIUSSS de l Estrie Centre Hospitalier Universitaire de Sherbrooke ( Site 0102)
🇨🇦Sherbrooke, Quebec, Canada
Institut Gustave Roussy ( Site 0243)
🇫🇷Villejuif, Val-de-Marne, France
Centre de Cancerologie du Grand Montpellier ( Site 0249)
🇫🇷Montpellier, Languedoc-Roussillon, France
Klinikum der Eberhard-Karls-Universitaet Tuebingen ( Site 0271)
🇩🇪Tuebingen, Baden-Wurttemberg, Germany
Universitaetsklinikum Giessen und Marburg GmbH ( Site 0284)
🇩🇪Marburg, Hessen, Germany
Centre Leon Berard ( Site 0244)
🇫🇷Lyon, Rhone, France
Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás Ce
🇭🇺Miskolc, Borsod-Abauj-Zemplen, Hungary
Rambam Medical Center ( Site 0552)
🇮🇱Haifa, Israel
CHD Vendee-onco-hematologie ( Site 0251)
🇫🇷La Roche sur Yon, Vendee, France
National Cancer Center Hospital East ( Site 0128)
🇯🇵Kashiwa, Chiba, Japan
Veterans Health Service Medical Center ( Site 0198)
🇰🇷Seoul, Korea, Republic of
Chonnam National University Hwasun Hospital ( Site 0194)
🇰🇷Hwasun Gun, Jeonranamdo, Korea, Republic of
Sapporo Medical University Hospital ( Site 0122)
🇯🇵Sapporo, Hokkaido, Japan
Shaare Zedek Medical Center ( Site 0559)
🇮🇱Jerusalem, Israel
Nara Medical University Hospital ( Site 0133)
🇯🇵Kashihara, Nara, Japan
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0301)
🇮🇹Milano, Italy
Centro di Riferimento Oncologico CRO ( Site 0304)
🇮🇹Aviano, Pordenone, Italy
Kitasato University Hospital ( Site 0129)
🇯🇵Sagamihara, Kanagawa, Japan
Medical Hospital, Tokyo Medical And Dental University ( Site 0130)
🇯🇵Tokyo, Japan
Rabin Medical Center ( Site 0553)
🇮🇱Petach-Tikwa, Israel
Chungnam National University Hospital ( Site 0195)
🇰🇷Daejeon, Taejon-Kwangyokshi, Korea, Republic of
Tokushima University Hospital ( Site 0134)
🇯🇵Tokushima, Japan
Policlinico S. Orsola - Malpighi (Bologna) ( Site 0302)
🇮🇹Bologna, Italy
Azienda Ospedaliera per l Emergenza Cannizzaro ( Site 0305)
🇮🇹Catania, Italy
Ehime University Hospital ( Site 0137)
🇯🇵Toon, Ehime, Japan
Maastricht Universitair Medisch Centrum - MUMC ( Site 0334)
🇳🇱Maastricht, Limburg, Netherlands
Yamaguchi University Hospital ( Site 0135)
🇯🇵Ube, Yamaguchi, Japan
Seoul National University Hospital ( Site 0191)
🇰🇷Seoul, Korea, Republic of
Medical Rehabilitation Center ( Site 0411)
🇷🇺Moscow, Moskva, Russian Federation
Murmansk Regional Oncology Dispensary ( Site 0420)
🇷🇺Murmansk, Murmanskaya Oblast, Russian Federation
National Cancer Center ( Site 0196)
🇰🇷Goyang-si, Kyonggi-do, Korea, Republic of
GBUZ Leningrad Regional Clinical Oncology Dispensary ( Site 0426)
🇷🇺Kuzmolovskiy Settlement, Leningradskaya Oblast, Russian Federation
Samsung Medical Center ( Site 0193)
🇰🇷Seoul, Korea, Republic of
Chiba Cancer Center ( Site 0127)
🇯🇵Chiba, Japan
VieCuri Medisch Centrum ( Site 0340)
🇳🇱Venlo, Limburg, Netherlands
Severance Hospital ( Site 0192)
🇰🇷Seoul, Korea, Republic of
Hirosaki University Hospital ( Site 0123)
🇯🇵Hirosaki, Aomori, Japan
Nagasaki University Hospital ( Site 0136)
🇯🇵Nagasaki, Japan
ICO L Hospitalet ( Site 0361)
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Korea University Anam Hospital ( Site 0197)
🇰🇷Seoul, Korea, Republic of
Akita University Hospital ( Site 0124)
🇯🇵Akita, Japan
Kaohsiung Medical University Chung-Ho Memorial Hospital ( Site 0216)
🇨🇳Kaoshiung, Kaohsiung, Taiwan
Kaohsiung Chang Gung Memorial Hospital ( Site 0217)
🇨🇳Kaohsiung, Taiwan
China Medical University Hospital ( Site 0213)
🇨🇳Taichung, Taiwan
Taichung Veterans General Hospital ( Site 0214)
🇨🇳Taichung, Taiwan
Central Clinical Hospital with Polyclinic ( Site 0415)
🇷🇺Moscow, Moskva, Russian Federation
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego ( Site 0535)
🇵🇱Wroclaw, Dolnoslaskie, Poland
Europejskie Centrum Zdrowia Otwock ( Site 0532)
🇵🇱Otwock, Mazowieckie, Poland
Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0454)
🇹🇷Istanbul, Turkey
Ziekenhuis Rijnstate ( Site 0342)
🇳🇱Arnhem, Gelderland, Netherlands
Hospital La Princesa ( Site 0862)
🇪🇸Madrid, Spain
Hospital Universitario Gregorio Maranon ( Site 0352)
🇪🇸Madrid, Spain
Clinical Hospital Saint Luka ( Site 0421)
🇷🇺Saint-Petersburg, Sankt-Peterburg, Russian Federation
Luxmed Onkologia sp. z o. o. ( Site 0541)
🇵🇱Warszawa, Mazowieckie, Poland
Saint Bartholomew s Hospital - London ( Site 0386)
🇬🇧London, London, City Of, United Kingdom
National Cheng Kung University Hospital ( Site 0215)
🇨🇳Tainan, Taiwan
Lister Hospital ( Site 0376)
🇬🇧Stevenage, Hertfordshire, United Kingdom
Sakarya Universitesi Tip Fakultesi Arastirma Hastanesi ( Site 0460)
🇹🇷Sakarya, Turkey
Volga District Medical Center Federal Medical and Biological Agency ( Site 0413)
🇷🇺Nizhny Novgorod, Nizhegorodskaya Oblast, Russian Federation
Russian Scientific Center of Roentgenoradiology ( Site 0424)
🇷🇺Moscow, Moskva, Russian Federation
Hospital General Universitari Vall d Hebron ( Site 0358)
🇪🇸Barcelona, Spain
Kent and Canterbury Hospital ( Site 0390)
🇬🇧Canterbury, Kent, United Kingdom
Hospital Infanta Cristina ( Site 0355)
🇪🇸Badajoz, Spain
University College London Hospital NHS Foundation Trust ( Site 0380)
🇬🇧London, London, City Of, United Kingdom
Ege Universitesi Tulay Aktas Onkoloji Hastanesi ( Site 0462)
🇹🇷İzmir, Turkey
Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi ( Site 0456)
🇹🇷Konya, Turkey
Hospital Teresa Herrera - Chuac ( Site 0357)
🇪🇸A Coruna, La Coruna, Spain
Nottingham University Hospital NHS Trust ( Site 0383)
🇬🇧Nottingham, United Kingdom
Cukurova Universitesi Tıp Fakultesi Balcalı Hastanesi ( Site 0457)
🇹🇷Adana, Turkey
Ankara Sehir Hastanesi ( Site 0455)
🇹🇷Ankara, Turkey
Taipei Veterans General Hospital ( Site 0212)
🇨🇳Taipei, Taiwan
Royal Preston Hospital ( Site 0379)
🇬🇧Preston, Lancashire, United Kingdom
Antalya Memorial Hospital Department of Medical Oncology ( Site 0461)
🇹🇷Antalya, Turkey
Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 0459)
🇹🇷Istanbul, Turkey
Imperial Healthcare NHS Trust Charing Cross Hospital ( Site 0378)
🇬🇧London, London, City Of, United Kingdom
Royal Stoke University Hospital Univ. Hosps of North Midlands NHST ( Site 0392)
🇬🇧Stoke-on-Trent, United Kingdom
Centre D Oncologie de Gentilly ( Site 0240)
🇫🇷Nancy, Meurthe-et-Moselle, France
Universitaetsklinikum Schleswig-Holstein-Campus Lubeck ( Site 0277)
🇩🇪Luebeck, Schleswig-Holstein, Germany
Institut de Cancerologie de l Ouest Site Paul Papin ( Site 0236)
🇫🇷Angers, Maine-et-Loire, France
Staedtisches Krankenhaus Kiel GmbH ( Site 0285)
🇩🇪Kiel, Schleswig-Holstein, Germany
Queens Hospital-Purple Zone ( Site 0377)
🇬🇧Romford, Essex, United Kingdom
Herlev Hospital ( Site 0681)
🇩🇰Herlev, Hovedstaden, Denmark
Aarhus Universitets hospital ( Site 0683)
🇩🇰Aarhus N, Midtjylland, Denmark
Aalborg Universitets Hospital ( Site 0684)
🇩🇰Aalborg, Nordjylland, Denmark
Odense Universitetshospital ( Site 0682)
🇩🇰Odense, Syddanmark, Denmark
Peking University First Hospital ( Site 0726)
🇨🇳Beijing, Beijing, China
Fifth Medical Center of CPLA General Hospital ( Site 0732)
🇨🇳Beijing, Beijing, China
Peking University Third Hospital ( Site 0727)
🇨🇳Beijing, Beijing, China
Chongqing Cancer Hospital ( Site 0741)
🇨🇳Chongging, Chongqing, China
Sun Yat-Sen University Cancer Center ( Site 0752)
🇨🇳Guangdong, Guangdong, China
Harbin Medical University Cancer Hospital ( Site 0750)
🇨🇳Harbin, Heilongjiang, China
Hunan Cancer Hospital ( Site 0745)
🇨🇳Changsha, Hunan, China
Hubei Cancer Hospital ( Site 0744)
🇨🇳Wuhan, Hubei, China
Nanjing Drum Tower Hospital ( Site 0737)
🇨🇳Nanjing, Jiangsu, China
Fudan University Shanghai Cancer Center ( Site 0721)
🇨🇳Shanghai, Shanghai, China
Zhongshan Hospital Fudan University ( Site 0725)
🇨🇳Shanghai, Shanghai, China
Second Affiliated Hospital, Zhejiang University ( Site 0734)
🇨🇳Hangzhou, Zhejiang, China
Cancer Hospital Affiliated to Xinjiang Medical University ( Site 0751)
🇨🇳Urumqi, Xinjiang, China
The First Affiliated Hospital of Xi an Jiaotong University ( Site 0738)
🇨🇳Xian, Shanxi, China
Zhejiang Provincial People's Hospital ( Site 0735)
🇨🇳Hangzhou, Zhejiang, China
Ospedale Borgo Roma-Oncologia ( Site 0308)
🇮🇹Verona, Italy
Derriford Hospital ( Site 0388)
🇬🇧Plymouth, United Kingdom
Osaka City University Hospital ( Site 0132)
🇯🇵Osaka, Japan
Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 0414)
🇷🇺Yaroslavl, Yaroslavskaya Oblast, Russian Federation
Omsk Clinical Oncology Dispensary ( Site 0418)
🇷🇺Omsk, Omskaya Oblast, Russian Federation
Centro de Investigaciones Clinicas - Clinica Viedma ( Site 0585)
🇦🇷Viedma, Rio Negro, Argentina
Ha Emek Medical Center ( Site 0560)
🇮🇱Afula, Israel
Assuta Ashdod Public ( Site 0562)
🇮🇱Ashdod, Israel
Hadassah Ein Kerem Medical Center ( Site 0558)
🇮🇱Jerusalem, Israel
Hospital Universitario HM Sanchinarro ( Site 0356)
🇪🇸Madrid, Madrid, Comunidad De, Spain
Istituto Tumori Giovanni Paolo II ( Site 0306)
🇮🇹Bari, Italy
Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0774)
🇺🇸Tulsa, Oklahoma, United States
Quincy Medical Group ( Site 0022)
🇺🇸Quincy, Illinois, United States
Cancer Care Northwest ( Site 0009)
🇺🇸Spokane, Washington, United States
Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 0577)
🇦🇷Berazategui, Buenos Aires, Argentina
New England Cancer Specialists ( Site 0047)
🇺🇸Scarborough, Maine, United States
Centro de Urología CDU ( Site 0590)
🇦🇷Buenos Aires, Caba, Argentina
Centro Oncologico de Integracion Regional. COIR ( Site 0576)
🇦🇷Mendoza, Argentina
Mater Misericordiae Ltd ( Site 0158)
🇦🇺South Brisbane, Queensland, Australia
Monash Health ( Site 0160)
🇦🇺Clayton, Victoria, Australia
Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0101)
🇨🇦Hamilton, Ontario, Canada
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University ( Site 0746)
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Xiamen University ( Site 0743)
🇨🇳Xiamen, Fujian, China
The First Affiliated Hospital of Guangzhou Medical University ( Site 0749)
🇨🇳Guangzhou, Guangdong, China
Rigshospitalet ( Site 0680)
🇩🇰Copenhagen, Hovedstaden, Denmark
Centre Rene Gauducheau ICO ( Site 0250)
🇫🇷Saint Herblain, Loire-Atlantique, France
Institut Curie ( Site 0237)
🇫🇷Paris, France
Universitaetsklinikum Essen ( Site 0274)
🇩🇪Essen, Nordrhein-Westfalen, Germany
Universitaetsklinikum Hamburg-Eppendorf ( Site 0282)
🇩🇪Hamburg, Germany
Bacs-Kiskun Megyei Korhaz ( Site 0510)
🇭🇺Kecskemet, Bacs-Kiskun, Hungary
Orszagos Onkologiai Intezet ( Site 0503)
🇭🇺Budapest, Hungary
Ospedale San Raffaele-Oncologia Medica ( Site 0309)
🇮🇹Milano, Lombardia, Italy
ASST Grande Ospedale Metropolitano Niguarda ( Site 0307)
🇮🇹Milano, Lombardia, Italy
Saitama Medical University International Medical Center ( Site 0125)
🇯🇵Hidaka, Saitama, Japan
Clinique Pasteur ( Site 0252)
🇫🇷Tolouse, Haute-Garonne, France
Urologica Praktyka Lekarska Adam Marcheluk ( Site 0543)
🇵🇱Siedlce, Mazowieckie, Poland
Szpital Miejski im. Jana Pawła II w Bielsku-Białej ( Site 0542)
🇵🇱Bielsko-Biala, Slaskie, Poland
Institut de Cancerologie Strasbourg Europe ( Site 0232)
🇫🇷Strasbourg, Alsace, France
Szpital Wojewodzki ( Site 1062)
🇵🇱Tarnow, Malopolskie, Poland
Weston Park Hospital ( Site 0387)
🇬🇧Sheffield, Derbyshire, United Kingdom
Karmanos Cancer Institute ( Site 0712)
🇺🇸Detroit, Michigan, United States
Comprehensive Cancer Centers of Nevada ( Site 0005)
🇺🇸Las Vegas, Nevada, United States
Medical University of South Carolina-Hollings Cancer Center ( Site 0029)
🇺🇸Charleston, South Carolina, United States
Virginia Cancer Institute ( Site 0099)
🇺🇸Richmond, Virginia, United States
Helios Kliniken Schwerin GmbH ( Site 0278)
🇩🇪Schwerin, Mecklenburg-Vorpommern, Germany
Xarxa Assistencial Universitaria Manresa ( Site 0354)
🇪🇸Manresa, Barcelona, Spain
Centro Oncológico de Rosario ( Site 0584)
🇦🇷Rosario, Santa Fe, Argentina
Institut Catala d Oncologia Hospital Germans Trias i Pujol ( Site 0351)
🇪🇸Badalona, Barcelona, Spain
Deventer Ziekenhuis ( Site 0341)
🇳🇱Deventer, Overijssel, Netherlands