Clinical trial NCT03898180: 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)
Official title: A Phase 3, Randomized, Double-blind Study to Compare the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Lenvatinib (E7080/MK-7902) Versus Pembrolizumab and Placebo as First Line Treatment for Locally Advanced or Metastatic Urothelial Carcinoma in Cisplatin-ineligible Participants Whose Tumors Express PD-L1, and in Participants Ineligible for Any Platinum-containing Chemotherapy Regardless of PD-L1 Expression (LEAP-011)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Urothelial Carcinoma
Keywords: Advanced or metastatic urothelial cancer
Lenvatinib
Pembrolizumab
Programmed Cell Death-1 (PD1, PD-1)
Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1)
Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Eisai Inc.
First posted: 2019-04-01
Enrollment: 505
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 25 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 25 months
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 25 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 25 months
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 25 months
measure: 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
timeFrame: Baseline and Week 11
measure: Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 GHS (Item 29) and QOL (Item 30) Combined Score
timeFrame: Baseline and up to approximately 25 months
measure: Number of Participants Who Experience an AE
timeFrame: Up to approximately 25 months
measure: Number of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 25 months
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center ( Site 0016)
state: Arizona
city: Clovis
country: United States
facility: Community Cancer Institute ( Site 0777)
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center ( Site 0078)
state: California
city: Santa Monica
country: United States
facility: John Wayne Cancer Institute ( Site 0017)
state: California
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers PC ( Site 0707)
state: Georgia
city: Chicago
country: United States
facility: University of Chicago ( Site 0039)
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology Hematology ( Site 0091)
state: Illinois
city: Quincy
country: United States
facility: Quincy Medical Group ( Site 0022)
state: Illinois
city: Scarborough
country: United States
facility: New England Cancer Specialists ( Site 0047)
state: Maine
city: Detroit
country: United States
facility: Karmanos Cancer Institute ( Site 0712)
state: Michigan
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis - David C. Pratt Cancer Center ( Site 0095)
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada ( Site 0005)
state: Nevada
city: Albany
country: United States
facility: St. Peter's Hospital Cancer Care Center ( Site 0042)
state: New York
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0002)
state: New York
city: Tulsa
country: United States
facility: Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0774)
state: Oklahoma
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital ( Site 0051)
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina-Hollings Cancer Center ( Site 0029)
state: South Carolina
city: Temple
country: United States
facility: Baylor Scott & White Medical Center - Temple ( Site 0706)
state: Texas
city: Richmond
country: United States
facility: Virginia Cancer Institute ( Site 0099)
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance ( Site 0003)
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest ( Site 0009)
state: Washington
city: Berazategui
country: Argentina
facility: Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 0577)
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Centro de Urología CDU ( Site 0590)
state: Caba
city: Buenos Aires
country: Argentina
facility: Instituto Medico Alexander Fleming ( Site 0578)
state: Caba
city: Viedma
country: Argentina
facility: Centro de Investigaciones Clinicas - Clinica Viedma ( Site 0585)
state: Rio Negro
city: Rosario
country: Argentina
facility: Centro Oncológico de Rosario ( Site 0584)
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Instituto de Investigaciones Metabolicas ( Site 0589)
city: Buenos Aires
country: Argentina
facility: Centro Medico Dra De Salvo ( Site 0593)
city: Cordoba
country: Argentina
facility: CEMAIC ( Site 0581)
city: Mendoza
country: Argentina
facility: Centro Oncologico de Integracion Regional. COIR ( Site 0576)
city: North Ryde
country: Australia
facility: Macquarie University ( Site 0151)
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Misericordiae Ltd ( Site 0158)
state: Queensland
city: Clayton
country: Australia
facility: Monash Health ( Site 0160)
state: Victoria
city: Frankston
country: Australia
facility: Peninsula Health Frankston Hospital ( Site 0153)
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health-Austin Hospital ( Site 0154)
state: Victoria
city: Hamilton
country: Canada
facility: Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0101)
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health ( Site 0103)
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute ( Site 0106)
state: Ontario
city: Sherbrooke
country: Canada
facility: CIUSSS de l Estrie Centre Hospitalier Universitaire de Sherbrooke ( Site 0102)
state: Quebec
city: Quebec
country: Canada
facility: CHUQ-Univ Laval-Hotel Dieu de Quebec ( Site 0104)
city: Beijing
country: China
facility: Peking University First Hospital ( Site 0726)
state: Beijing
city: Beijing
country: China
facility: Fifth Medical Center of CPLA General Hospital ( Site 0732)
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital ( Site 0727)
state: Beijing
city: Chongging
country: China
facility: Chongqing Cancer Hospital ( Site 0741)
state: Chongqing
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University ( Site 0743)
state: Fujian
city: Guangdong
country: China
facility: Sun Yat-Sen University Cancer Center ( Site 0752)
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University ( Site 0749)
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University ( Site 0746)
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital ( Site 0750)
state: Heilongjiang
city: Wuhan
country: China
facility: Hubei Cancer Hospital ( Site 0744)
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital ( Site 0745)
state: Hunan
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital ( Site 0737)
state: Jiangsu
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center ( Site 0721)
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University ( Site 0725)
state: Shanghai
city: Xian
country: China
facility: The First Affiliated Hospital of Xi an Jiaotong University ( Site 0738)
state: Shanxi
city: Urumqi
country: China
facility: Cancer Hospital Affiliated to Xinjiang Medical University ( Site 0751)
state: Xinjiang
city: Hangzhou
country: China
facility: Second Affiliated Hospital, Zhejiang University ( Site 0734)
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital ( Site 0735)
state: Zhejiang
city: Copenhagen
country: Denmark
facility: Rigshospitalet ( Site 0680)
state: Hovedstaden
city: Herlev
country: Denmark
facility: Herlev Hospital ( Site 0681)
state: Hovedstaden
city: Aarhus N
country: Denmark
facility: Aarhus Universitets hospital ( Site 0683)
state: Midtjylland
city: Aalborg
country: Denmark
facility: Aalborg Universitets Hospital ( Site 0684)
state: Nordjylland
city: Odense
country: Denmark
facility: Odense Universitetshospital ( Site 0682)
state: Syddanmark
city: Poitiers
country: France
facility: CHU Poitiers ( Site 0253)
state: Ain
city: Strasbourg
country: France
facility: Institut de Cancerologie Strasbourg Europe ( Site 0232)
state: Alsace
city: Marseille
country: France
facility: Hopital de la Timone ( Site 0246)
state: Bouches-du-Rhone
city: Quimper
country: France
facility: CHIC Quimper ( Site 0245)
state: Finistere
city: Bordeaux
country: France
facility: CHU de Bordeaux- Hopital Saint Andre ( Site 0235)
state: Gironde
city: Tolouse
country: France
facility: Clinique Pasteur ( Site 0252)
state: Haute-Garonne
city: Montpellier
country: France
facility: Centre de Cancerologie du Grand Montpellier ( Site 0249)
state: Languedoc-Roussillon
city: Saint Herblain
country: France
facility: Centre Rene Gauducheau ICO ( Site 0250)
state: Loire-Atlantique
city: Angers
country: France
facility: Institut de Cancerologie de l Ouest Site Paul Papin ( Site 0236)
state: Maine-et-Loire
city: Nancy
country: France
facility: Centre D Oncologie de Gentilly ( Site 0240)
state: Meurthe-et-Moselle
city: Bayonne
country: France
facility: Centre Hospitalier de la Cote Basque ( Site 0239)
state: Pyrenees-Atlantiques
city: Lyon
country: France
facility: Centre Leon Berard ( Site 0244)
state: Rhone
city: Villejuif
country: France
facility: Institut Gustave Roussy ( Site 0243)
state: Val-de-Marne
city: La Roche sur Yon
country: France
facility: CHD Vendee-onco-hematologie ( Site 0251)
state: Vendee
city: Paris
country: France
facility: Institut Curie ( Site 0237)
city: Tuebingen
country: Germany
facility: Klinikum der Eberhard-Karls-Universitaet Tuebingen ( Site 0271)
state: Baden-Wurttemberg
city: Marburg
country: Germany
facility: Universitaetsklinikum Giessen und Marburg GmbH ( Site 0284)
state: Hessen
city: Schwerin
country: Germany
facility: Helios Kliniken Schwerin GmbH ( Site 0278)
state: Mecklenburg-Vorpommern
city: Gottingen
country: Germany
facility: Universitaetsmedizin Goettingen ( Site 0281)
state: Niedersachsen
city: Essen
country: Germany
facility: Universitaetsklinikum Essen ( Site 0274)
state: Nordrhein-Westfalen
city: Kiel
country: Germany
facility: Staedtisches Krankenhaus Kiel GmbH ( Site 0285)
state: Schleswig-Holstein
city: Luebeck
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein-Campus Lubeck ( Site 0277)
state: Schleswig-Holstein
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf ( Site 0282)
city: Kecskemet
country: Hungary
facility: Bacs-Kiskun Megyei Korhaz ( Site 0510)
state: Bacs-Kiskun
city: Miskolc
country: Hungary
facility: Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás Ce
state: Borsod-Abauj-Zemplen
city: Szolnok
country: Hungary
facility: Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 0507)
state: Jasz-Nagykun-Szolnok
city: Szombathely
country: Hungary
facility: Markusovszky Egyetemi Oktatokorhaz ( Site 0502)
state: Vas
city: Budapest
country: Hungary
facility: Bajcsy Zsilinszki Korhaz es Rendelointezet ( Site 0509)
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet ( Site 0503)
city: Budapest
country: Hungary
facility: Uzsoki Utcai Korhaz ( Site 0508)
city: Kaposvar
country: Hungary
facility: Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 0504)
city: Afula
country: Israel
facility: Ha Emek Medical Center ( Site 0560)
city: Ashdod
country: Israel
facility: Assuta Ashdod Public ( Site 0562)
city: Haifa
country: Israel
facility: Rambam Medical Center ( Site 0552)
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center ( Site 0559)
city: Jerusalem
country: Israel
facility: Hadassah Ein Kerem Medical Center ( Site 0558)
city: Kfar Saba
country: Israel
facility: Meir Medical Center ( Site 0554)
city: Petach-Tikwa
country: Israel
facility: Rabin Medical Center ( Site 0553)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center ( Site 0551)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 0561)
city: Zerifin
country: Israel
facility: Assaf Harofeh Medical Center ( Site 0556)
city: Milano
country: Italy
facility: Ospedale San Raffaele-Oncologia Medica ( Site 0309)
state: Lombardia
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda ( Site 0307)
state: Lombardia
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico CRO ( Site 0304)
state: Pordenone
city: Bari
country: Italy
facility: Istituto Tumori Giovanni Paolo II ( Site 0306)
city: Bologna
country: Italy
facility: Policlinico S. Orsola - Malpighi (Bologna) ( Site 0302)
city: Catania
country: Italy
facility: Azienda Ospedaliera per l Emergenza Cannizzaro ( Site 0305)
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0301)
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria ( Site 0303)
city: Verona
country: Italy
facility: Ospedale Borgo Roma-Oncologia ( Site 0308)
city: Hirosaki
country: Japan
facility: Hirosaki University Hospital ( Site 0123)
state: Aomori
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East ( Site 0128)
state: Chiba
city: Toon
country: Japan
facility: Ehime University Hospital ( Site 0137)
state: Ehime
city: Sapporo
country: Japan
facility: Sapporo Medical University Hospital ( Site 0122)
state: Hokkaido
city: Tsukuba
country: Japan
facility: University of Tsukuba Hospital ( Site 0126)
state: Ibaraki
city: Sagamihara
country: Japan
facility: Kitasato University Hospital ( Site 0129)
state: Kanagawa
city: Kashihara
country: Japan
facility: Nara Medical University Hospital ( Site 0133)
state: Nara
city: Hidaka
country: Japan
facility: Saitama Medical University International Medical Center ( Site 0125)
state: Saitama
city: Ube
country: Japan
facility: Yamaguchi University Hospital ( Site 0135)
state: Yamaguchi
city: Akita
country: Japan
facility: Akita University Hospital ( Site 0124)
city: Chiba
country: Japan
facility: Chiba Cancer Center ( Site 0127)
city: Nagasaki
country: Japan
facility: Nagasaki University Hospital ( Site 0136)
city: Osaka
country: Japan
facility: Osaka City University Hospital ( Site 0132)
city: Tokushima
country: Japan
facility: Tokushima University Hospital ( Site 0134)
city: Tokyo
country: Japan
facility: Medical Hospital, Tokyo Medical And Dental University ( Site 0130)
city: Hwasun Gun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital ( Site 0194)
state: Jeonranamdo
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center ( Site 0196)
state: Kyonggi-do
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital ( Site 0195)
state: Taejon-Kwangyokshi
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital ( Site 0197)
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 0191)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital ( Site 0192)
city: Seoul
country: Korea, Republic of
facility: Veterans Health Service Medical Center ( Site 0198)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 0193)
city: Arnhem
country: Netherlands
facility: Ziekenhuis Rijnstate ( Site 0342)
state: Gelderland
city: Maastricht
country: Netherlands
facility: Maastricht Universitair Medisch Centrum - MUMC ( Site 0334)
state: Limburg
city: Venlo
country: Netherlands
facility: VieCuri Medisch Centrum ( Site 0340)
state: Limburg
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis Breda ( Site 0331)
state: Noord-Brabant
city: Deventer
country: Netherlands
facility: Deventer Ziekenhuis ( Site 0341)
state: Overijssel
city: Den Haag
country: Netherlands
facility: Haga Ziekenhuis ( Site 0333)
state: Zuid-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus MC ( Site 0332)
state: Zuid-Holland
city: Utrecht
country: Netherlands
facility: St. Antonius Ziekenhuis ( Site 0335)
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego ( Site 0535)
state: Dolnoslaskie
city: Tarnow
country: Poland
facility: Szpital Wojewodzki ( Site 1062)
state: Malopolskie
city: Otwock
country: Poland
facility: Europejskie Centrum Zdrowia Otwock ( Site 0532)
state: Mazowieckie
city: Siedlce
country: Poland
facility: Urologica Praktyka Lekarska Adam Marcheluk ( Site 0543)
state: Mazowieckie
city: Warszawa
country: Poland
facility: Luxmed Onkologia sp. z o. o. ( Site 0541)
state: Mazowieckie
city: Bielsko-Biala
country: Poland
facility: Szpital Miejski im. Jana Pawła II w Bielsku-Białej ( Site 0542)
state: Slaskie
city: Kuzmolovskiy Settlement
country: Russian Federation
facility: GBUZ Leningrad Regional Clinical Oncology Dispensary ( Site 0426)
state: Leningradskaya Oblast
city: Moscow
country: Russian Federation
facility: Russian Scientific Center of Roentgenoradiology ( Site 0424)
state: Moskva
city: Moscow
country: Russian Federation
facility: Central Clinical Hospital with Polyclinic ( Site 0415)
state: Moskva
city: Moscow
country: Russian Federation
facility: Medical Rehabilitation Center ( Site 0411)
state: Moskva
city: Murmansk
country: Russian Federation
facility: Murmansk Regional Oncology Dispensary ( Site 0420)
state: Murmanskaya Oblast
city: Nizhny Novgorod
country: Russian Federation
facility: Volga District Medical Center Federal Medical and Biological Agency ( Site 0413)
state: Nizhegorodskaya Oblast
city: Omsk
country: Russian Federation
facility: Omsk Clinical Oncology Dispensary ( Site 0418)
state: Omskaya Oblast
city: Saint-Petersburg
country: Russian Federation
facility: Clinical Hospital Saint Luka ( Site 0421)
state: Sankt-Peterburg
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 0414)
state: Yaroslavskaya Oblast
city: Badalona
country: Spain
facility: Institut Catala d Oncologia Hospital Germans Trias i Pujol ( Site 0351)
state: Barcelona
city: Hospitalet de Llobregat
country: Spain
facility: ICO L Hospitalet ( Site 0361)
state: Barcelona
city: Manresa
country: Spain
facility: Xarxa Assistencial Universitaria Manresa ( Site 0354)
state: Barcelona
city: A Coruna
country: Spain
facility: Hospital Teresa Herrera - Chuac ( Site 0357)
state: La Coruna
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro ( Site 0356)
state: Madrid, Comunidad De
city: Badajoz
country: Spain
facility: Hospital Infanta Cristina ( Site 0355)
city: Barcelona
country: Spain
facility: Hospital General Universitari Vall d Hebron ( Site 0358)
city: Madrid
country: Spain
facility: Hospital La Princesa ( Site 0862)
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Maranon ( Site 0352)
city: Kaoshiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital ( Site 0216)
state: Kaohsiung
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital ( Site 0217)
city: Taichung
country: Taiwan
facility: China Medical University Hospital ( Site 0213)
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital ( Site 0214)
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital ( Site 0215)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital ( Site 0211)
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital ( Site 0212)
city: Adana
country: Turkey
facility: Cukurova Universitesi Tıp Fakultesi Balcalı Hastanesi ( Site 0457)
city: Ankara
country: Turkey
facility: Ankara Sehir Hastanesi ( Site 0455)
city: Antalya
country: Turkey
facility: Antalya Memorial Hospital Department of Medical Oncology ( Site 0461)
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0454)
city: Istanbul
country: Turkey
facility: Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 0459)
city: İzmir
country: Turkey
facility: Ege Universitesi Tulay Aktas Onkoloji Hastanesi ( Site 0462)
city: Konya
country: Turkey
facility: Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi ( Site 0456)
city: Sakarya
country: Turkey
facility: Sakarya Universitesi Tip Fakultesi Arastirma Hastanesi ( Site 0460)
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital ( Site 0387)
state: Derbyshire
city: Romford
country: United Kingdom
facility: Queens Hospital-Purple Zone ( Site 0377)
state: Essex
city: Stevenage
country: United Kingdom
facility: Lister Hospital ( Site 0376)
state: Hertfordshire
city: Canterbury
country: United Kingdom
facility: Kent and Canterbury Hospital ( Site 0390)
state: Kent
city: Preston
country: United Kingdom
facility: Royal Preston Hospital ( Site 0379)
state: Lancashire
city: London
country: United Kingdom
facility: Saint Bartholomew s Hospital - London ( Site 0386)
state: London, City Of
city: London
country: United Kingdom
facility: University College London Hospital NHS Foundation Trust ( Site 0380)
state: London, City Of
city: London
country: United Kingdom
facility: Imperial Healthcare NHS Trust Charing Cross Hospital ( Site 0378)
state: London, City Of
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospital NHS Trust ( Site 0383)
city: Plymouth
country: United Kingdom
facility: Derriford Hospital ( Site 0388)
city: Stoke-on-Trent
country: United Kingdom
facility: Royal Stoke University Hospital Univ. Hosps of North Midlands NHST ( Site 0392)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Matsubara N, de Wit R, Balar AV, Siefker-Radtke AO, Zolnierek J, Csoszi T, Shin SJ, Park SH, Atduev V, Gumus M, Su YL, Karaca SB, Cutuli HJ, Sendur MAN, Shen L, O'Hara K, Okpara CE, Franco S, Moreno BH, Grivas P, Loriot Y. Pembrolizumab with or Without Lenvatinib as First-line Therapy for Patients with Advanced Urothelial Carcinoma (LEAP-011): A Phase 3, Randomized, Double-Blind Trial. Eur Urol. 2024 Mar;85(3):229-238. doi: 10.1016/j.eururo.2023.08.012. Epub 2023 Sep 29.
citation: Taylor MH, Schmidt EV, Dutcus C, Pinheiro EM, Funahashi Y, Lubiniecki G, Rasco D. The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. Future Oncol. 2021 Feb;17(6):637-648. doi: 10.2217/fon-2020-0937. Epub 2020 Dec 10.