Clinical trial NCT03829319: Safety and Efficacy Study of Pemetrexed + Platinum Chemotherapy + Pembrolizumab (MK-3475) With or Without Lenvatinib (MK-7902/E7080) as First-line Intervention in Adults With Metastatic Nonsquamous Non-small Cell Lung Cancer (MK-7902-006/E7080-G000-315/LEAP-006)
Official title: A Phase 3 Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Pemetrexed + Platinum Chemotherapy + Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) as First-line Intervention in Participants With Metastatic Nonsquamous Non-small Cell Lung Cancer (LEAP-006)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Nonsquamous Non-small Cell Lung Cancer
Keywords: programmed cell death 1 (PD-1, PD1)
programmed cell death-ligand 1 (PD-L1, PDL1)
programmed cell death-ligand 2 (PD-L2, PDL2)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Eisai Inc.
First posted: 2019-02-04
Enrollment: 761
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 assess the safety and efficacy of pemetrexed + platinum chemotherapy + pembrolizumab (MK-3475) with or without lenvatinib (MK-7902/E7080) as first-line intervention in adults with metastatic nonsquamous non-small cell lung cancer.

The primary study hypotheses state that: 1) the combination of lenvatinib + platinum doublet chemotherapy + pembrolizumab prolongs Progression-free Survival (PFS) as assessed by blinded independent central review (BICR) per modified Response Evaluation Criteria in Solid Tumors version 1.1 (RESIST 1.1) compared to matching placebo + platinum doublet chemotherapy + pembrolizumab, and 2) the combination of lenvatinib + platinum doublet chemotherapy + pembrolizumab prolongs Overall Survival (OS) compared to matching placebo + platinum doublet chemotherapy + pembrolizumab.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed diagnosis of Stage IV (American Joint Committee on Cancer \[AJCC\], version 8 or current version), nonsquamous NSCLC.
* Confirmation that Epidermal Growth Factor Receptor (EGFR), ALK Receptor Tyrosine Kinase (ALK), or ROS1 Receptor Tyrosine Kinase (ROS1)-directed therapy is not indicated as primary treatment (documentation of absence of tumor-activating EGFR mutations AND absence of ALK and ROS1 gene rearrangements OR presence of a Kirsten Rat Sarcoma (KRAS) gene mutation).
* Have measurable disease based on RECIST 1.1. Note: Lesions that appear measurable, but are situated in a previously irradiated area, can be considered measurable (eligible for selection as target lesions) if they have shown documented growth since the completion of radiation.
* Provided an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion (not previously irradiated).
* Life expectancy of at least 3 months.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of study intervention but before randomization.
* Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
* Male participants must agree for at least 7 days after the last dose of lenvatinib/matching placebo and up to 180 days after the last dose of chemotherapeutic agents to:

  1. Refrain from donating sperm PLUS either:
  2. Be abstinence from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR
  3. Must agree to use contraception unless confirmed to be azoopsermic (vasectomized or secondary to medical cause) as detailed below:

     1. Agree 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.

Note: 7 days after lenvatinib/matching placebo is stopped, if the participant is on pembrolizumab only and is greater than 180 days post chemotherapy, no male contraception measures are needed.

* Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* Female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:

  1. Is not a WOCBP OR
  2. Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days post pembrolizumab and/or 30 days post-lenvatinib/matching placebo, and up to 180 days post last dose of chemotherapeutic agents, whichever occurs last.
* Adequate organ function.
* Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg and no change in antihypertensive medications within 1 week prior to randomization. Note: Participants must not have a history of uncontrolled or poorly-controlled hypertension, defined as \>150/90 mm Hg for \>4 weeks despite standard medical management.

Exclusion Criteria:

* Known untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, clinically stable, and have not required steroids for at least 14 days prior to the first dose of study intervention.
* History of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
* Radiographic evidence of intratumoral caviations, encasement, or invasion of a major blood vessel. Additionally, the degree of proximity to major blood vessels should be considered for exclusion because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis after lenvatinib-therapy. (In the chest, major blood vessels include the main pulmonary artery, the left and right pulmonary arteries, the 4 major pulmonary veins, the superior or inferior vena cava, and the aorta).
* Known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy. Note: The time requirement also does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers.
* Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.
* Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention.
* Has had allogeneic tissue/solid organ transplant.
* Known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by the local health authority.
* Known history of Hepatitis B or active Hepatitis C. No testing for Hepatitis B or Hepatitis C is required unless mandated by the local health authority.
* History of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral drug absorption.
* Active hemoptysis (at least 0.5 teaspoon of bright red blood) within 2 weeks prior to the first dose of study intervention.
* Significant cardiovascular impairment within 12 months prior to the first dose of study intervention, including history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, cerebrovascular accident (CVA)/stroke, or cardiac arrhythmia associated with hemodynamic instability.
* Known history of active tuberculosis.
* Active infection requiring systemic therapy.
* Has not recovered adequately from any toxicity and/or complication from major surgery prior to the first dose of study intervention.
* Previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity to any component of lenvatinib or pembrolizumab, or as applicable, carboplatin, cisplatin, or pemetrexed.
* A WOCBP who has a positive urine pregnancy test within 24 hours prior to randomization or treatment allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
* Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula.
* Received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC. Note: Prior treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic NSCLC.
* Received prior treatment with pembrolizumab or any other anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2 agent, with lenvatinib or any other receptor tyrosine kinase inhibitor (RTKi), or with an agent directed to another stimulatory or co-inhibitory T cell receptor.
* Received radiotherapy within 14 days prior to the first dose of study intervention or received lung radiation therapy of \>30 Gy within 6 months prior to the first dose of study intervention. Note: Participants must have recovered from all radiation-related toxicities to Grade ≤1, not required corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
* Received systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) within 7 days prior to the first dose of study intervention.
* Received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention. Note: killed vaccines are allowed.
* Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of study intervention.
* Has a prolongation of QTc interval (calculated using Fridericia's formula) of \>480 msecl.
* Left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).
* Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula

Primary outcomes:
measure: Part 1: Number of Participants With a Dose-limiting Toxicity (DLT)
timeFrame: Cycle 1; each cycle is 21 days (up to 21 days)
measure: Part 1: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 48 months
measure: Part 1: Number of Participants Who Discontinued Study Drug Due to an Adverse Event
timeFrame: Up to approximately 48 months
measure: Part 2: Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to approximately 36 months
measure: Part 2: Overall Survival (OS)
timeFrame: Up to approximately 47 months
Secondary outcomes:
measure: Part 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to approximately 19 months
measure: Part 2: Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to approximately 48 months
measure: Part 2: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 45 months
measure: Part 2: Number of Participants Who Discontinued Study Drug Due to an Adverse Event
timeFrame: Up to approximately 45 months
measure: Part 2: Change From Baseline in Global Health Status (GHS) (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [EORTC QLQ-C30] Items 29 and 30) Score
timeFrame: Baseline and Week 27
measure: Part 2: Change From Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer Module 13 [QLQ-LC13] Item 31) Score
timeFrame: Baseline and week 27
measure: Part 2: Change From Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) Score
timeFrame: Baseline and Week 27
measure: Part 2: Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score
timeFrame: Baseline and Week 27
measure: Part 2: Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score
timeFrame: Baseline and Week 27
measure: Part 2: Time to True Deterioration (TTD) Based on Change From Baseline in Global Health Status (GHS)/Quality of Life (QoL) (EORTC QLQ-C30 Items 29 and 30) Score
timeFrame: Baseline and Week 27
measure: Part 2: TTD Based on Change From Baseline in Cough EORTC QLQ-LC13 (Item 31) Score
timeFrame: Baseline And Week 27
measure: Part 2: TTD Based on Change From Baseline in Chest Pain EORTC QLQ-LC13 (Item 40) Score
timeFrame: Baseline and Week 27
measure: Part 2: TTD Based on Change From Baseline in Dyspnea EORTC QLQ-C30 (Item 8) Score
timeFrame: Baseline and Week 27
measure: Part 2: TTD Based on Change From Baseline in Physical Functioning EORTC QLQ-C30 (Items 1 Through 5) Score
timeFrame: Baseline and Week 27
measure: Part 2: Time to True Deterioration (TTD) Based on Change From Baseline in the Composite Endpoint of Cough (EORTC QLQ-LC13 Item 31), Chest Pain (EORTC QLQ-LC13 Item 40), or Dyspnea (EORTC QLQ-C30 Item 8)
timeFrame: Baseline and Week 27
Other outcomes:
Locations:
city: Mountain View
country: United States
facility: El Camino Hospital Cancer Center ( Site 0529)
state: California
city: New Haven
country: United States
facility: Yale University ( Site 0519)
state: Connecticut
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital ( Site 0512)
state: Florida
city: Paducah
country: United States
facility: Mercy Health-Paducah Medical Oncology and Hematology ( Site 0570)
state: Kentucky
city: Detroit
country: United States
facility: Henry Ford Health System ( Site 0563)
state: Michigan
city: Kansas City
country: United States
facility: Saint Lukes Cancer Institute ( Site 0541)
state: Missouri
city: Johnson City
country: United States
facility: Broome Oncology, LLC ( Site 0562)
state: New York
city: Fargo
country: United States
facility: Sanford Health Roger Maris Cancer Center ( Site 0533)
state: North Dakota
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center ( Site 0504)
state: Oklahoma
city: Corvallis
country: United States
facility: Good Samaritan Hospital Corvallis ( Site 0521)
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital ( Site 0548)
state: Pennsylvania
city: Willow Grove
country: United States
facility: Abington Hospital - Asplundh Cancer Center ( Site 0575)
state: Pennsylvania
city: Germantown
country: United States
facility: West Cancer Center - East Campus ( Site 0544)
state: Tennessee
city: Dallas
country: United States
facility: Parkland Health & Hospital System ( Site 0576)
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center ( Site 0558)
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists ( Site 0523)
state: Utah
city: Morgantown
country: United States
facility: West Virginia University ( Site 0526)
state: West Virginia
city: Berazategui
country: Argentina
facility: Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 0367)
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Instituto de Investigaciones Clinicas Mar del Plata ( Site 0371)
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: CEMIC ( Site 0370)
state: Caba
city: Rosario
country: Argentina
facility: Sanatorio Parque ( Site 0365)
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Hospital Aleman ( Site 0368)
city: Buenos Aires
country: Argentina
facility: Instituto Medico Especializado Alexander Fleming ( Site 0369)
city: Cordoba
country: Argentina
facility: CEMAIC ( Site 0374)
city: San Juan
country: Argentina
facility: CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica ( Site 0372)
city: Blacktown
country: Australia
facility: Blacktown Hospital Western Sydney Local Health District ( Site 0008)
state: New South Wales
city: Port Macquarie
country: Australia
facility: Port Macquarie Base Hospital ( Site 0001)
state: New South Wales
city: Sydney
country: Australia
facility: Chris OBrien Lifehouse ( Site 0006)
state: New South Wales
city: Sydney
country: Australia
facility: Westmead Hospital ( Site 0009)
state: New South Wales
city: Cairns
country: Australia
facility: Cairns Hospital ( Site 0002)
state: Queensland
city: Chermside
country: Australia
facility: The Prince Charles Hospital ( Site 0010)
state: Queensland
city: Ballarat
country: Australia
facility: Ballarat Health Services ( Site 0003)
state: Victoria
city: Moncton
country: Canada
facility: Moncton Hospital - Horizon Health Network ( Site 0410)
state: New Brunswick
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre ( Site 0407)
state: Ontario
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre ( Site 0414)
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health ( Site 0406)
state: Ontario
city: Sault Ste Marie
country: Canada
facility: Sault Area Hospital ( Site 0413)
state: Ontario
city: Laval
country: Canada
facility: Hopital Cite de la Sante de Laval ( Site 0400)
state: Quebec
city: Montreal
country: Canada
facility: CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0412)
state: Quebec
city: Trois-Rivieres
country: Canada
facility: CIUSSS de la Mauricie et du Centre du Quebec ( Site 0408)
state: Quebec
city: Quebec
country: Canada
facility: CHU de Quebec-Universite Laval-Hotel Dieu de Quebec ( Site 0403)
city: Temuco
country: Chile
facility: Centro de Investigacion y desarrollo Oncologico SpA - CIDO SpA ( Site 0380)
state: Araucania
city: Talca
country: Chile
facility: Clinica Universidad Catolica del Maule ( Site 0385)
state: Maule
city: Santiago
country: Chile
facility: OrlandiOncologia ( Site 0381)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Fundacion Arturo Lopez Perez FALP ( Site 0383)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Pontificia Universidad Catolica de Chile ( Site 0382)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Bradford Hill Centro de Investigaciones Clinicas ( Site 0387)
state: Region M. De Santiago
city: Vina del Mar
country: Chile
facility: Oncocentro ( Site 0384)
state: Valparaiso
city: Antofagasta
country: Chile
facility: Centro Oncologico Antofagasta ( Site 0386)
city: Beijing
country: China
facility: Peking Union Medical College Hospital ( Site 0108)
state: Beijing
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Science ( Site 0117)
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital ( Site 0120)
state: Beijing
city: Chongqing
country: China
facility: The Second Hospital Affiliated to AMU ( Site 0119)
state: Chongqing
city: Chongqing
country: China
facility: First Affiliated Hospital of The Third Military Medical University ( Site 0118)
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital ( Site 0102)
state: Fujian
city: Guangzhou
country: China
facility: Southern Medical University Nanfang Hospital ( Site 0121)
state: Guangdong
city: Harbin
country: China
facility: The Third Affiliated Hospital of Harbin Medical University ( Site 0100)
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital ( Site 0112)
state: Henan
city: Wuhan
country: China
facility: Wuhan Union Hospital Cancer Center-Cancer Center ( Site 0123)
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital ( Site 0122)
state: Hubei
city: Changchun
country: China
facility: Jilin Cancer Hospital ( Site 0115)
state: Jilin
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University ( Site 0103)
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital ( Site 0101)
state: Shanghai
city: Tian Jin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital ( Site 0111)
state: Tianjin
city: Urumuqi
country: China
facility: Cancer Hospital Affiliated to Xinjiang Medical University ( Site 0110)
state: Xinjiang
city: Hangzhou
country: China
facility: The First Affiliated Hospital Zhejiang University ( Site 0109)
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital ( Site 0113)
state: Zhejiang
city: Wen Zhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University ( Site 0124)
state: Zhejiang
city: Strasbourg
country: France
facility: Centre Paul Strauss ( Site 0144)
state: Bas-Rhin
city: Marseille
country: France
facility: Hopital Nord du Marseille ( Site 0147)
state: Bouches-du-Rhone
city: Suresnes
country: France
facility: Hopital Foch ( Site 0145)
state: Hauts-de-Seine
city: Montpellier
country: France
facility: Centre de Cancerologie du Grand Montpellier ( Site 0142)
state: Herault
city: Nantes cedex 1
country: France
facility: Hopital Laennec ( Site 0146)
state: Loire-Atlantique
city: Vantoux
country: France
facility: Hopital Robert Schuman ( Site 0143)
state: Moselle
city: Bron
country: France
facility: Hopital Cardiologique Louis Pradel ( Site 0141)
state: Rhone-Alpes
city: Villefranche sur Saone
country: France
facility: L'hopital Nord-Ouest - Centre Hospitalier de Villefranche sur Saone ( Site 0149)
state: Rhone
city: Paris
country: France
facility: Hopital Cochin ( Site 0140)
city: Esslingen
country: Germany
facility: Klinikum Esslingen GmbH ( Site 0164)
state: Baden-Wurttemberg
city: Frankfurt
country: Germany
facility: Krankenhaus Nordwest ( Site 0169)
state: Hessen
city: Oldenburg
country: Germany
facility: Pius Hospital Oldenburg ( Site 0170)
state: Niedersachsen
city: Aachen
country: Germany
facility: Uniklinik RWTH Aachen ( Site 0160)
state: Nordrhein-Westfalen
city: Homburg
country: Germany
facility: Universitaetsklinikum des Saarlandes ( Site 0165)
state: Saarland
city: Halle
country: Germany
facility: Krankenhaus Martha Maria Halle-Doelau ( Site 0166)
state: Sachsen-Anhalt
city: Grosshansdorf
country: Germany
facility: LungenClinic Grosshansdorf GmbH ( Site 0171)
state: Schleswig-Holstein
city: Hamburg
country: Germany
facility: Hamato-Onkologie Hamburg Prof. Laack und Partner ( Site 0161)
city: Beer Sheva
country: Israel
facility: Soroka Medical Center ( Site 0222)
city: Haifa
country: Israel
facility: Rambam Medical Center ( Site 0223)
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center-Oncology ( Site 0229)
city: Kfar Saba
country: Israel
facility: Meir Medical Center ( Site 0221)
city: Nazareth
country: Israel
facility: Holy Family Hospital ( Site 0228)
city: Petah Tikva
country: Israel
facility: Rabin Medical Center ( Site 0224)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center ( Site 0220)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 0225)
city: Zerifin
country: Israel
facility: Shamir Medical Center-Assaf Harofeh ( Site 0227)
city: Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center ( Site 0017)
state: Aichi
city: Toyoake
country: Japan
facility: Fujita Health University Hospital ( Site 0016)
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East ( Site 0024)
state: Chiba
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital ( Site 0018)
state: Ishikawa
city: Habikino
country: Japan
facility: Osaka Habikino Medical Center ( Site 0020)
state: Osaka
city: Hirakata
country: Japan
facility: Kansai Medical University Hospital ( Site 0022)
state: Osaka
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital ( Site 0019)
city: Tokyo
country: Japan
facility: National Cancer Center Hospital ( Site 0026)
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Komagome Hospital ( Site 0015)
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR ( Site 0021)
city: Wakayama
country: Japan
facility: Wakayama Medical University Hospital ( Site 0025)
city: Cheongju si
country: Korea, Republic of
facility: Chungbuk National University Hospital ( Site 0062)
state: Chungbuk
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center ( Site 0061)
state: Kyonggi-do
city: Gyeonggi-do
country: Korea, Republic of
facility: The Catholic University of Korea St. Vincent s Hospital ( Site 0064)
state: Kyonggi-do
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System ( Site 0063)
city: Tauranga
country: New Zealand
facility: Tauranga Hospital ( Site 0004)
state: Bay Of Plenty
city: Auckland
country: New Zealand
facility: Auckland City Hospital ( Site 0011)
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im.prof. F. Lukaszczyka w Bydgoszczy ( Site 0601)
state: Kujawsko-pomorskie
city: Lodz
country: Poland
facility: Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii ( Site 0613)
state: Lodzkie
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0603)
state: Mazowieckie
city: Pleszew
country: Poland
facility: Pleszewskie Centrum Medyczne w Pleszewie Sp. z o.o. ( Site 0615)
state: Wielkopolskie
city: Poznan
country: Poland
facility: MED-POLONIA Sp. z o.o. ( Site 0609)
state: Wielkopolskie
city: Koszalin
country: Poland
facility: Szpital Wojewodzki im. Mikolaja Kopernika ( Site 0602)
state: Zachodniopomorskie
city: Saint Petersburg
country: Russian Federation
facility: Leningrad Regional Oncology Center ( Site 0271)
state: Leningradskaya Oblast
city: Balashikha
country: Russian Federation
facility: Moscow Regional Oncological Dispensary ( Site 0274)
state: Moskovskaya Oblast
city: Moscow
country: Russian Federation
facility: City Clinical Hospital 1 na. NI. Pirogov ( Site 0270)
state: Moskva
city: Moscow
country: Russian Federation
facility: Central Clinical Hospital with outpatient Clinic ( Site 0262)
state: Moskva
city: Moscow
country: Russian Federation
facility: National Medical Research Radiology Centre ( Site 0260)
state: Moskva
city: Moscow
country: Russian Federation
facility: FSAI Treatment and Rehabilitation Centre of the MoH and SD of RF ( Site 0264)
state: Moskva
city: Nizhniy Novgorod
country: Russian Federation
facility: Nizhniy Novgorod Region Oncology Dispensary ( Site 0272)
state: Nizhegorodskaya Oblast
city: Omsk
country: Russian Federation
facility: Omsk Clinical Oncology Dispensary ( Site 0267)
state: Omskaya Oblast
city: Saint Petersburg
country: Russian Federation
facility: Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 0269)
state: Sankt-Peterburg
city: Saint-Petersburg
country: Russian Federation
facility: First Pavlov State Medical University of Saint Petersburg-Department of Oncology ( Site 0273)
state: Sankt-Peterburg
city: Kazan
country: Russian Federation
facility: SAHI Republican Clinical Oncological Dispensary of the MoH of RT ( Site 0261)
state: Tatarstan, Respublika
city: Hospitalet de Llobregat
country: Spain
facility: ICO L Hospitalet ( Site 0234)
state: Barcelona
city: A Coruna
country: Spain
facility: Complejo Hospitalario Universitario A Coruna ( Site 0239)
state: La Coruna
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Universitario Insular de Gran Canaria ( Site 0244)
state: Las Palmas
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia ( Site 0231)
state: Valenciana, Comunitat
city: Valencia
country: Spain
facility: Hospital Universitario La Fe ( Site 0233)
state: Valenciana, Comunitat
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante ( Site 0240)
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau ( Site 0241)
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon ( Site 0237)
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos ( Site 0235)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz ( Site 0236)
city: Malaga
country: Spain
facility: Complejo Hospitalario de Malaga ( Site 0238)
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet ( Site 0242)
city: Adana
country: Turkey
facility: Cukurova Universitesi Tıp Fakultesi Balcalı Hastanesi ( Site 0314)
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tıp Fakultesi ( Site 0316)
city: Ankara
country: Turkey
facility: Ankara Universitesi Tip Fakultesi. ( Site 0317)
city: Ankara
country: Turkey
facility: Ankara Sehir Hastanesi ( Site 0323)
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0312)
city: Istanbul
country: Turkey
facility: Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 0310)
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi ( Site 0313)
city: Malatya
country: Turkey
facility: Inonu Universitesi Medical Fakultesi ( Site 0318)
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Trust ( Site 0293)
state: Cambridgeshire
city: London
country: United Kingdom
facility: North Middlesex University Hospital NHS Trust ( Site 0291)
state: London, City Of
city: London
country: United Kingdom
facility: Guys and St Thomas NHS Foundation Trust ( Site 0280)
state: London, City Of
city: London
country: United Kingdom
facility: St Georges University Hospitals NHS Foundation Trust. ( Site 0292)
state: London, City Of
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary ( Site 0288)
state: Scotland
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospital NHS Trust. St. James University Hospital ( Site 0276)
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary ( Site 0284)
city: Manchester
country: United Kingdom
facility: Christie NHS Foundation Trust ( Site 0275)
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital Campus ( Site 0287)
city: Wirral
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust ( Site 0286)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: