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)
Study Details
Study Description
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:
-
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
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Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Overall Survival (OS).
With Amendment 3 study treatment with lenvatinib and placebo was discontinued and all participants were unblinded and continued treatment with pembrolizumab monotherapy only. The pembrolizumab+lenvatinib and the pembrolizumab+placebo arms are no longer active for this study.
With Amendment 3 the external Data Monitoring Committee was discontinued.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pembrolizumab+Lenvatinib Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles (approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) until progressive disease or discontinuation. Lenvatinib may be continued past 35 cycles until a discontinuation criterion is met. |
Biological: Pembrolizumab
IV infusion
Other Names:
Drug: Lenvatinib
oral capsule
Other Names:
|
| Active Comparator: Pembrolizumab+Placebo Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD until progressive disease or discontinuation. Placebo may be continued past 35 cycles until a discontinuation criterion is met. |
Biological: Pembrolizumab
IV infusion
Other Names:
Drug: Placebo for lenvatinib
oral capsule
|
| Experimental: Pembrolizumab monotherapy Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (approximately 2 years) until progressive disease or discontinuation. Pembrolizumab may be continued past 35 cycles until a discontinuation criterion is met. |
Biological: Pembrolizumab
IV infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) [Up to approximately 40 months]
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of ≥1 new lesions is also considered PD.
- Overall Survival (OS) [Up to approximately 40 months]
OS is defined as the time from randomization to the date of death from any cause.
Secondary Outcome Measures
- Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) [Up to approximately 40 months]
ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1.
- Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) [Up to approximately 40 months]
DOR is defined as the time from the first documented evidence of Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) to the earliest date of progressive disease (PD; per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of ≥1 new lesions is also considered PD) or death due to any cause, whichever comes first, for participants with a confirmed CR or PR.
- Disease Control Rate (DCR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) [Up to approximately 40 months]
DCR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: ≥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 progressive disease [PD: ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. Note: The appearance of ≥1 new lesions is also considered PD.])
- Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score [Baseline and up to approximately 40 months]
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are 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 will be presented. A higher score indicates a better outcome.
- Time to Deterioration (TTD) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score [Up to approximately 40 months]
TTD is defined as the time from baseline to the first onset of a ≥10-point negative change (decrease) from baseline in Global Health Status (GHS; EORTC QLQ-C30 Item 29) & Quality of Life (QoL; EORTC QLQ-C30 Item 30) combined score. Using linear transformation, raw scores are 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, will be presented. A longer TTD indicates a better outcome.
- Number of Participants Who Experience an Adverse Event (AE) [Up to approximately 40 months]
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
- Number of Participants Who Discontinue Study Treatment Due to an AE [Up to approximately 40 months]
The number of participants who discontinue study treatment due to an AE will be presented.
Eligibility Criteria
Criteria
Inclusion Criteria:
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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.
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Has ≥1 measurable target lesion per RECIST 1.1 as assessed by the local site investigator/radiologist.
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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.
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Has received no prior systemic chemotherapy for advanced or metastatic UC with the following exceptions:
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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.
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Adjuvant (following surgery) platinum-based chemotherapy following radical cystectomy, with recurrence >12 months from completion of the therapy, is permitted.
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Meets criteria for either option a or option b (below):
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- 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:
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Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 2 within 7 days prior to randomization
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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
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- In the opinion of the investigator, is considered ineligible to receive any platinum-based chemotherapy (i.e., ineligible for cisplatin and carboplatin) based on:
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ECOG PS of 2 within 7 days prior to randomization. and ≥1 of the following:
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Documented visceral metastatic disease
-
NCI CTCAE Version 4.0 Grade ≥2 audiometric hearing loss
-
NCI CTCAE Version 4.0 Grade ≥2 peripheral neuropathy
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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.
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Has ECOG PS 0, 1, or 2 within 7 days prior to randomization and a life expectancy of ≥3 months.
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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
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Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause as detailed below:
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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.
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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.
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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.
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Has adequate organ function.
Exclusion Criteria:
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Has disease that is suitable for local therapy administered with curative intent (e.g. chemotherapy and radiation for Stage 3 disease).
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Has tumor with any neuroendocrine or small cell component.
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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.
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Has had major surgery within 3 weeks prior to the first dose of study treatment
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Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula.
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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.
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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.
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Has known intolerance or severe hypersensitivity (Grade ≥3) to pembrolizumab or lenvatinib or any of their excipients
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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.
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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.
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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.
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Has received a live vaccine within 30 days prior to the first dose of study treatment.
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In the investigator's judgment, has not recovered from toxicity or other complications from any major surgery prior to starting study treatment.
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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.
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Has history or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful.
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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.
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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.
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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.
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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.
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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).
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Has a history of (non-infectious) pneumonitis that required systemic steroids, or current pneumonitis.
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Has an active infection requiring systemic therapy.
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Has a known history of human immunodeficiency virus (HIV) infection.
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Has a known history of or is positive for active hepatitis B virus (HBV) or has active hepatitis C virus (HCV).
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Has active tuberculosis (TB).
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Is receiving hemodialysis.
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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.
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Has had an allogeneic tissue/solid organ transplant.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Banner MD Anderson Cancer Center ( Site 0016) | Gilbert | Arizona | United States | 85234 |
| 2 | Community Cancer Institute ( Site 0777) | Clovis | California | United States | 93611 |
| 3 | University of California Irvine Medical Center ( Site 0078) | Orange | California | United States | 92868 |
| 4 | John Wayne Cancer Institute ( Site 0017) | Santa Monica | California | United States | 90404 |
| 5 | Northwest Georgia Oncology Centers PC ( Site 0707) | Marietta | Georgia | United States | 30060 |
| 6 | University of Chicago ( Site 0039) | Chicago | Illinois | United States | 60637 |
| 7 | Joliet Oncology Hematology ( Site 0091) | Joliet | Illinois | United States | 60436 |
| 8 | Quincy Medical Group ( Site 0022) | Quincy | Illinois | United States | 62301 |
| 9 | New England Cancer Specialists ( Site 0047) | Scarborough | Maine | United States | 04074 |
| 10 | Karmanos Cancer Institute ( Site 0712) | Detroit | Michigan | United States | 48201 |
| 11 | Mercy Hospital Saint Louis - David C. Pratt Cancer Center ( Site 0095) | Saint Louis | Missouri | United States | 63141 |
| 12 | Comprehensive Cancer Centers of Nevada ( Site 0005) | Las Vegas | Nevada | United States | 89169 |
| 13 | St. Peter's Hospital Cancer Care Center ( Site 0042) | Albany | New York | United States | 12208 |
| 14 | Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0002) | New York | New York | United States | 10016 |
| 15 | Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0774) | Tulsa | Oklahoma | United States | 74146 |
| 16 | Thomas Jefferson University Hospital ( Site 0051) | Philadelphia | Pennsylvania | United States | 19107 |
| 17 | Medical University of South Carolina-Hollings Cancer Center ( Site 0029) | Charleston | South Carolina | United States | 29425 |
| 18 | Baylor Scott & White Medical Center - Temple ( Site 0706) | Temple | Texas | United States | 76508 |
| 19 | Virginia Cancer Institute ( Site 0099) | Richmond | Virginia | United States | 23230 |
| 20 | Seattle Cancer Care Alliance ( Site 0003) | Seattle | Washington | United States | 98109 |
| 21 | Cancer Care Northwest ( Site 0009) | Spokane | Washington | United States | 99218 |
| 22 | Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 0577) | Berazategui | Buenos Aires | Argentina | B1884BBF |
| 23 | Centro de Urología CDU ( Site 0590) | Buenos Aires | Caba | Argentina | C1120AAT |
| 24 | Instituto Medico Alexander Fleming ( Site 0578) | Buenos Aires | Caba | Argentina | C1426ANZ |
| 25 | Centro de Investigaciones Clinicas - Clinica Viedma ( Site 0585) | Viedma | Rio Negro | Argentina | R8500ACE |
| 26 | Centro Oncológico de Rosario ( Site 0584) | Rosario | Santa Fe | Argentina | S2000KZE |
| 27 | Instituto de Investigaciones Metabolicas ( Site 0589) | Buenos Aires | Argentina | C1012AAR | |
| 28 | Centro Medico Dra De Salvo ( Site 0593) | Buenos Aires | Argentina | C1426ANZ | |
| 29 | CEMAIC ( Site 0581) | Cordoba | Argentina | X5008HHW | |
| 30 | Centro Oncologico de Integracion Regional. COIR ( Site 0576) | Mendoza | Argentina | M5500AYB | |
| 31 | Macquarie University ( Site 0151) | North Ryde | New South Wales | Australia | 2109 |
| 32 | Mater Misericordiae Ltd ( Site 0158) | South Brisbane | Queensland | Australia | 4101 |
| 33 | Monash Health ( Site 0160) | Clayton | Victoria | Australia | 3168 |
| 34 | Peninsula Health Frankston Hospital ( Site 0153) | Frankston | Victoria | Australia | 3199 |
| 35 | Austin Health-Austin Hospital ( Site 0154) | Heidelberg | Victoria | Australia | 3084 |
| 36 | Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0101) | Hamilton | Ontario | Canada | L8V 5C2 |
| 37 | Lakeridge Health ( Site 0103) | Oshawa | Ontario | Canada | L1G 2B9 |
| 38 | Sunnybrook Research Institute ( Site 0106) | Toronto | Ontario | Canada | M4N 3M5 |
| 39 | CIUSSS de l Estrie Centre Hospitalier Universitaire de Sherbrooke ( Site 0102) | Sherbrooke | Quebec | Canada | J1H5N4 |
| 40 | CHUQ-Univ Laval-Hotel Dieu de Quebec ( Site 0104) | Quebec | Canada | G1R 2J6 | |
| 41 | Peking University First Hospital ( Site 0726) | Beijing | Beijing | China | 100034 |
| 42 | Fifth Medical Center of CPLA General Hospital ( Site 0732) | Beijing | Beijing | China | 100071 |
| 43 | Peking University Third Hospital ( Site 0727) | Beijing | Beijing | China | 100089 |
| 44 | Chongqing Cancer Hospital ( Site 0741) | Chongging | Chongqing | China | 400030 |
| 45 | The First Affiliated Hospital of Xiamen University ( Site 0743) | Xiamen | Fujian | China | 361003 |
| 46 | Sun Yat-Sen University Cancer Center ( Site 0752) | Guangdong | Guangdong | China | 510060 |
| 47 | The First Affiliated Hospital of Guangzhou Medical University ( Site 0749) | Guangzhou | Guangdong | China | 510230 |
| 48 | Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University ( Site 0746) | Guangzhou | Guangdong | China | 510289 |
| 49 | Harbin Medical University Cancer Hospital ( Site 0750) | Harbin | Heilongjiang | China | 150081 |
| 50 | Hubei Cancer Hospital ( Site 0744) | Wuhan | Hubei | China | 430079 |
| 51 | Hunan Cancer Hospital ( Site 0745) | Changsha | Hunan | China | 410013 |
| 52 | Nanjing Drum Tower Hospital ( Site 0737) | Nanjing | Jiangsu | China | 210008 |
| 53 | Fudan University Shanghai Cancer Center ( Site 0721) | Shanghai | Shanghai | China | 200032 |
| 54 | Zhongshan Hospital Fudan University ( Site 0725) | Shanghai | Shanghai | China | 200032 |
| 55 | The First Affiliated Hospital of Xi an Jiaotong University ( Site 0738) | Xian | Shanxi | China | 710061 |
| 56 | Cancer Hospital Affiliated to Xinjiang Medical University ( Site 0751) | Urumqi | Xinjiang | China | 830011 |
| 57 | Second Affiliated Hospital, Zhejiang University ( Site 0734) | Hangzhou | Zhejiang | China | 310009 |
| 58 | Zhejiang Provincial People's Hospital ( Site 0735) | Hangzhou | Zhejiang | China | 310014 |
| 59 | Rigshospitalet ( Site 0680) | Copenhagen | Hovedstaden | Denmark | 2100 |
| 60 | Herlev Hospital ( Site 0681) | Herlev | Hovedstaden | Denmark | 2730 |
| 61 | Aarhus Universitets hospital ( Site 0683) | Aarhus N | Midtjylland | Denmark | 8200 |
| 62 | Aalborg Universitets Hospital ( Site 0684) | Aalborg | Nordjylland | Denmark | 9000 |
| 63 | Odense Universitetshospital ( Site 0682) | Odense | Syddanmark | Denmark | 5000 |
| 64 | CHU Poitiers ( Site 0253) | Poitiers | Ain | France | 86021 |
| 65 | Institut de Cancerologie Strasbourg Europe ( Site 0232) | Strasbourg | Alsace | France | 67033 |
| 66 | Hopital de la Timone ( Site 0246) | Marseille | Bouches-du-Rhone | France | 13005 |
| 67 | CHIC Quimper ( Site 0245) | Quimper | Finistere | France | 29107 |
| 68 | CHU de Bordeaux- Hopital Saint Andre ( Site 0235) | Bordeaux | Gironde | France | 33075 |
| 69 | Clinique Pasteur ( Site 0252) | Tolouse | Haute-Garonne | France | 31076 |
| 70 | Centre de Cancerologie du Grand Montpellier ( Site 0249) | Montpellier | Languedoc-Roussillon | France | 34070 |
| 71 | Centre Rene Gauducheau ICO ( Site 0250) | Saint Herblain | Loire-Atlantique | France | 44805 |
| 72 | Institut de Cancerologie de l Ouest Site Paul Papin ( Site 0236) | Angers | Maine-et-Loire | France | 49055 |
| 73 | Centre D Oncologie de Gentilly ( Site 0240) | Nancy | Meurthe-et-Moselle | France | 54100 |
| 74 | Centre Hospitalier de la Cote Basque ( Site 0239) | Bayonne | Pyrenees-Atlantiques | France | 64109 |
| 75 | Centre Leon Berard ( Site 0244) | Lyon | Rhone | France | 69373 |
| 76 | Institut Gustave Roussy ( Site 0243) | Villejuif | Val-de-Marne | France | 94805 |
| 77 | CHD Vendee-onco-hematologie ( Site 0251) | La Roche sur Yon | Vendee | France | 85925 |
| 78 | Institut Curie ( Site 0237) | Paris | France | 75005 | |
| 79 | Klinikum der Eberhard-Karls-Universitaet Tuebingen ( Site 0271) | Tuebingen | Baden-Wurttemberg | Germany | 72076 |
| 80 | Universitaetsklinikum Giessen und Marburg GmbH ( Site 0284) | Marburg | Hessen | Germany | 35032 |
| 81 | Helios Kliniken Schwerin GmbH ( Site 0278) | Schwerin | Mecklenburg-Vorpommern | Germany | 19049 |
| 82 | Universitaetsmedizin Goettingen ( Site 0281) | Gottingen | Niedersachsen | Germany | 37075 |
| 83 | Universitaetsklinikum Essen ( Site 0274) | Essen | Nordrhein-Westfalen | Germany | 45147 |
| 84 | Staedtisches Krankenhaus Kiel GmbH ( Site 0285) | Kiel | Schleswig-Holstein | Germany | 24116 |
| 85 | Universitaetsklinikum Schleswig-Holstein-Campus Lubeck ( Site 0277) | Luebeck | Schleswig-Holstein | Germany | 23538 |
| 86 | Universitaetsklinikum Hamburg-Eppendorf ( Site 0282) | Hamburg | Germany | 20246 | |
| 87 | Bacs-Kiskun Megyei Korhaz ( Site 0510) | Kecskemet | Bacs-Kiskun | Hungary | 6000 |
| 88 | Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás Ce | Miskolc | Borsod-Abauj-Zemplen | Hungary | 3526 |
| 89 | Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 0507) | Szolnok | Jasz-Nagykun-Szolnok | Hungary | 5000 |
| 90 | Markusovszky Egyetemi Oktatokorhaz ( Site 0502) | Szombathely | Vas | Hungary | 9400 |
| 91 | Bajcsy Zsilinszki Korhaz es Rendelointezet ( Site 0509) | Budapest | Hungary | 1106 | |
| 92 | Orszagos Onkologiai Intezet ( Site 0503) | Budapest | Hungary | 1122 | |
| 93 | Uzsoki Utcai Korhaz ( Site 0508) | Budapest | Hungary | 1145 | |
| 94 | Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 0504) | Kaposvar | Hungary | 7400 | |
| 95 | Ha Emek Medical Center ( Site 0560) | Afula | Israel | 1834111 | |
| 96 | Assuta Ashdod Public ( Site 0562) | Ashdod | Israel | 7747629 | |
| 97 | Rambam Medical Center ( Site 0552) | Haifa | Israel | 3109601 | |
| 98 | Shaare Zedek Medical Center ( Site 0559) | Jerusalem | Israel | 9103102 | |
| 99 | Hadassah Ein Kerem Medical Center ( Site 0558) | Jerusalem | Israel | 9112001 | |
| 100 | Meir Medical Center ( Site 0554) | Kfar Saba | Israel | 4428164 | |
| 101 | Rabin Medical Center ( Site 0553) | Petach-Tikwa | Israel | 4941492 | |
| 102 | Sheba Medical Center ( Site 0551) | Ramat Gan | Israel | 5265601 | |
| 103 | Sourasky Medical Center ( Site 0561) | Tel Aviv | Israel | 6423906 | |
| 104 | Assaf Harofeh Medical Center ( Site 0556) | Zerifin | Israel | 70300 | |
| 105 | Ospedale San Raffaele-Oncologia Medica ( Site 0309) | Milano | Lombardia | Italy | 20132 |
| 106 | ASST Grande Ospedale Metropolitano Niguarda ( Site 0307) | Milano | Lombardia | Italy | 20162 |
| 107 | Centro di Riferimento Oncologico CRO ( Site 0304) | Aviano | Pordenone | Italy | 33081 |
| 108 | Istituto Tumori Giovanni Paolo II ( Site 0306) | Bari | Italy | 70124 | |
| 109 | Policlinico S. Orsola - Malpighi (Bologna) ( Site 0302) | Bologna | Italy | 40138 | |
| 110 | Azienda Ospedaliera per l Emergenza Cannizzaro ( Site 0305) | Catania | Italy | 95126 | |
| 111 | Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0301) | Milano | Italy | 20133 | |
| 112 | Azienda Ospedaliera Santa Maria ( Site 0303) | Terni | Italy | 05100 | |
| 113 | Ospedale Borgo Roma-Oncologia ( Site 0308) | Verona | Italy | 37134 | |
| 114 | Hirosaki University Hospital ( Site 0123) | Hirosaki | Aomori | Japan | 036-8563 |
| 115 | National Cancer Center Hospital East ( Site 0128) | Kashiwa | Chiba | Japan | 277-8577 |
| 116 | Ehime University Hospital ( Site 0137) | Toon | Ehime | Japan | 791-0295 |
| 117 | Sapporo Medical University Hospital ( Site 0122) | Sapporo | Hokkaido | Japan | 060-8543 |
| 118 | University of Tsukuba Hospital ( Site 0126) | Tsukuba | Ibaraki | Japan | 305-8576 |
| 119 | Kitasato University Hospital ( Site 0129) | Sagamihara | Kanagawa | Japan | 252-0375 |
| 120 | Nara Medical University Hospital ( Site 0133) | Kashihara | Nara | Japan | 634-8522 |
| 121 | Saitama Medical University International Medical Center ( Site 0125) | Hidaka | Saitama | Japan | 350-1298 |
| 122 | Yamaguchi University Hospital ( Site 0135) | Ube | Yamaguchi | Japan | 755-8505 |
| 123 | Akita University Hospital ( Site 0124) | Akita | Japan | 010-8543 | |
| 124 | Chiba Cancer Center ( Site 0127) | Chiba | Japan | 260-8717 | |
| 125 | Nagasaki University Hospital ( Site 0136) | Nagasaki | Japan | 852-8501 | |
| 126 | Osaka City University Hospital ( Site 0132) | Osaka | Japan | 545-8586 | |
| 127 | Tokushima University Hospital ( Site 0134) | Tokushima | Japan | 770-8503 | |
| 128 | Medical Hospital, Tokyo Medical And Dental University ( Site 0130) | Tokyo | Japan | 113-8519 | |
| 129 | Chonnam National University Hwasun Hospital ( Site 0194) | Hwasun Gun | Jeonranamdo | Korea, Republic of | 58128 |
| 130 | National Cancer Center ( Site 0196) | Goyang-si | Kyonggi-do | Korea, Republic of | 10408 |
| 131 | Chungnam National University Hospital ( Site 0195) | Daejeon | Taejon-Kwangyokshi | Korea, Republic of | 35015 |
| 132 | Korea University Anam Hospital ( Site 0197) | Seoul | Korea, Republic of | 02841 | |
| 133 | Seoul National University Hospital ( Site 0191) | Seoul | Korea, Republic of | 03080 | |
| 134 | Severance Hospital ( Site 0192) | Seoul | Korea, Republic of | 03722 | |
| 135 | Veterans Health Service Medical Center ( Site 0198) | Seoul | Korea, Republic of | 05368 | |
| 136 | Samsung Medical Center ( Site 0193) | Seoul | Korea, Republic of | 06351 | |
| 137 | Ziekenhuis Rijnstate ( Site 0342) | Arnhem | Gelderland | Netherlands | 6815 AD |
| 138 | Maastricht Universitair Medisch Centrum - MUMC ( Site 0334) | Maastricht | Limburg | Netherlands | 6229 HX |
| 139 | VieCuri Medisch Centrum ( Site 0340) | Venlo | Limburg | Netherlands | 5912 BL |
| 140 | Amphia Ziekenhuis Breda ( Site 0331) | Breda | Noord-Brabant | Netherlands | 4819 EV |
| 141 | Deventer Ziekenhuis ( Site 0341) | Deventer | Overijssel | Netherlands | 7416 SE |
| 142 | Haga Ziekenhuis ( Site 0333) | Den Haag | Zuid-Holland | Netherlands | 2545 AA |
| 143 | Erasmus MC ( Site 0332) | Rotterdam | Zuid-Holland | Netherlands | 3015 GD |
| 144 | St. Antonius Ziekenhuis ( Site 0335) | Utrecht | Netherlands | 3543 AZ | |
| 145 | Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego ( Site 0535) | Wroclaw | Dolnoslaskie | Poland | 50-556 |
| 146 | Szpital Wojewodzki ( Site 1062) | Tarnow | Malopolskie | Poland | 33-100 |
| 147 | Europejskie Centrum Zdrowia Otwock ( Site 0532) | Otwock | Mazowieckie | Poland | 05-400 |
| 148 | Urologica Praktyka Lekarska Adam Marcheluk ( Site 0543) | Siedlce | Mazowieckie | Poland | 08-110 |
| 149 | Luxmed Onkologia sp. z o. o. ( Site 0541) | Warszawa | Mazowieckie | Poland | 01-748 |
| 150 | Szpital Miejski im. Jana Pawła II w Bielsku-Białej ( Site 0542) | Bielsko-Biala | Slaskie | Poland | 43-300 |
| 151 | GBUZ Leningrad Regional Clinical Oncology Dispensary ( Site 0426) | Kuzmolovskiy Settlement | Leningradskaya Oblast | Russian Federation | 188663 |
| 152 | Russian Scientific Center of Roentgenoradiology ( Site 0424) | Moscow | Moskva | Russian Federation | 117485 |
| 153 | Central Clinical Hospital with Polyclinic ( Site 0415) | Moscow | Moskva | Russian Federation | 121359 |
| 154 | Medical Rehabilitation Center ( Site 0411) | Moscow | Moskva | Russian Federation | 125367 |
| 155 | Murmansk Regional Oncology Dispensary ( Site 0420) | Murmansk | Murmanskaya Oblast | Russian Federation | 183057 |
| 156 | Volga District Medical Center Federal Medical and Biological Agency ( Site 0413) | Nizhny Novgorod | Nizhegorodskaya Oblast | Russian Federation | 603074 |
| 157 | Omsk Clinical Oncology Dispensary ( Site 0418) | Omsk | Omskaya Oblast | Russian Federation | 644013 |
| 158 | Clinical Hospital Saint Luka ( Site 0421) | Saint-Petersburg | Sankt-Peterburg | Russian Federation | 194044 |
| 159 | Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 0414) | Yaroslavl | Yaroslavskaya Oblast | Russian Federation | 150054 |
| 160 | Institut Catala d Oncologia Hospital Germans Trias i Pujol ( Site 0351) | Badalona | Barcelona | Spain | 08916 |
| 161 | ICO L Hospitalet ( Site 0361) | Hospitalet de Llobregat | Barcelona | Spain | 08908 |
| 162 | Xarxa Assistencial Universitaria Manresa ( Site 0354) | Manresa | Barcelona | Spain | 08243 |
| 163 | Hospital Teresa Herrera - Chuac ( Site 0357) | A Coruna | La Coruna | Spain | 15006 |
| 164 | Hospital Universitario HM Sanchinarro ( Site 0356) | Madrid | Madrid, Comunidad De | Spain | 28050 |
| 165 | Hospital Infanta Cristina ( Site 0355) | Badajoz | Spain | 06080 | |
| 166 | Hospital General Universitari Vall d Hebron ( Site 0358) | Barcelona | Spain | 08035 | |
| 167 | Hospital La Princesa ( Site 0862) | Madrid | Spain | 28006 | |
| 168 | Hospital Universitario Gregorio Maranon ( Site 0352) | Madrid | Spain | 28009 | |
| 169 | Kaohsiung Medical University Chung-Ho Memorial Hospital ( Site 0216) | Kaoshiung | Kaohsiung | Taiwan | 807 |
| 170 | Kaohsiung Chang Gung Memorial Hospital ( Site 0217) | Kaohsiung | Taiwan | 83301 | |
| 171 | China Medical University Hospital ( Site 0213) | Taichung | Taiwan | 40447 | |
| 172 | Taichung Veterans General Hospital ( Site 0214) | Taichung | Taiwan | 40705 | |
| 173 | National Cheng Kung University Hospital ( Site 0215) | Tainan | Taiwan | 70403 | |
| 174 | National Taiwan University Hospital ( Site 0211) | Taipei | Taiwan | 100 | |
| 175 | Taipei Veterans General Hospital ( Site 0212) | Taipei | Taiwan | 11217 | |
| 176 | Cukurova Universitesi Tıp Fakultesi Balcalı Hastanesi ( Site 0457) | Adana | Turkey | 01330 | |
| 177 | Ankara Sehir Hastanesi ( Site 0455) | Ankara | Turkey | 06800 | |
| 178 | Antalya Memorial Hospital Department of Medical Oncology ( Site 0461) | Antalya | Turkey | 07020 | |
| 179 | Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0454) | Istanbul | Turkey | 34098 | |
| 180 | Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 0459) | Istanbul | Turkey | 34722 | |
| 181 | Ege Universitesi Tulay Aktas Onkoloji Hastanesi ( Site 0462) | İzmir | Turkey | 35100 | |
| 182 | Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi ( Site 0456) | Konya | Turkey | 42080 | |
| 183 | Sakarya Universitesi Tip Fakultesi Arastirma Hastanesi ( Site 0460) | Sakarya | Turkey | 54290 | |
| 184 | Weston Park Hospital ( Site 0387) | Sheffield | Derbyshire | United Kingdom | S10 2SJ |
| 185 | Queens Hospital-Purple Zone ( Site 0377) | Romford | Essex | United Kingdom | RM7 0AG |
| 186 | Lister Hospital ( Site 0376) | Stevenage | Hertfordshire | United Kingdom | SG1 4AB |
| 187 | Kent and Canterbury Hospital ( Site 0390) | Canterbury | Kent | United Kingdom | CT1 3NG |
| 188 | Royal Preston Hospital ( Site 0379) | Preston | Lancashire | United Kingdom | PR2 9HT |
| 189 | Saint Bartholomew s Hospital - London ( Site 0386) | London | London, City Of | United Kingdom | EC1A 7BE |
| 190 | University College London Hospital NHS Foundation Trust ( Site 0380) | London | London, City Of | United Kingdom | NW1 2PG |
| 191 | Imperial Healthcare NHS Trust Charing Cross Hospital ( Site 0378) | London | London, City Of | United Kingdom | W6 8RF |
| 192 | Nottingham University Hospital NHS Trust ( Site 0383) | Nottingham | United Kingdom | NG5 1PB | |
| 193 | Derriford Hospital ( Site 0388) | Plymouth | United Kingdom | PL6 8DH | |
| 194 | Royal Stoke University Hospital Univ. Hosps of North Midlands NHST ( Site 0392) | Stoke-on-Trent | United Kingdom | ST4 6QG |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
- Eisai Inc.
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 7902-011
- MK-7902-011
- E7080-G000-317
- LEAP-011
- 194808
- 2018-003752-21