Clinical trial NCT03725059: Study of Pembrolizumab (MK-3475) Versus Placebo in Combination With Neoadjuvant Chemotherapy & Adjuvant Endocrine Therapy in the Treatment of Early-Stage Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer (MK-3475-756/KEYNOTE-756)
Official title: A Randomized, Double-Blind, Phase III Study of Pembrolizumab Versus Placebo in Combination With Neoadjuvant Chemotherapy and Adjuvant Endocrine Therapy for the Treatment of High-Risk Early-Stage Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer (KEYNOTE-756)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Keywords: PD1
PD-1
PDL1
PD-L1
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2018-10-30
Enrollment: 1240
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 efficacy and safety of pembrolizumab (MK-3475) versus placebo in combination with neoadjuvant (pre-surgery) chemotherapy and adjuvant (post-surgery) endocrine therapy in the treatment of adults who have high-risk early-stage estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer.

The primary study hypotheses are: 1) pembrolizumab is superior to placebo, both in combination with the protocol-specified neoadjuvant anticancer therapy, as assessed by pathological Complete Response (pCR) rate defined by the local pathologist, and 2) pembrolizumab is superior to placebo (both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies) as assessed by Event-Free Survival (EFS) as determined by the investigator. The study is considered to have met its primary objective if pembrolizumab is superior to placebo with respect to either pCR (ypT0/Tis ypN0) or EFS.

Detailed description: Study participants will receive 8 cycles of neoadjuvant study treatment and then will undergo surgery for their breast cancer. After surgery, participants will receive 9 cycles of study treatment and up to 10 years of variable endocrine therapy. Each cycle is 21 days long.

Eligibility criteria: Inclusion Criteria:

* Has a localized invasive breast ductal adenocarcinoma, confirmed by the local pathologist, that includes either T1c-T2 (tumor size ≥2 cm), clinical node stage (cN)1-cN2, or T3-T4, cN0-cN2. Note: Inflammatory breast cancer is allowed.
* Has centrally confirmed ER+/HER2-, Grade 3 breast cancer of ductal histology, according to the most recent American Society of Clinical Oncology/College of American Pathologist guidelines.
* Provides a new or recently obtained core needle biopsy, consisting of multiple cores, taken from the primary breast tumor(s) for central determination of HR status (ER and progesterone receptor), HER2, grade, and PD-L1 status.

Note: Sponsor agreement is required for formalin-fixed paraffin-embedded (FFPE) tumor tissue sample or slides that were obtained greater than 60 days prior to the date that the documented informed consent was obtained.

* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 10 days prior to initiation of study treatment.
* Male participants must agree to use contraception during the treatment period and for at least 12 months (for participants who received cyclophosphamide) or 6 months (for participants who did not receive cyclophosphamide) after the last dose of study treatment and refrain from donating sperm during this period.
* Female participants must agree to use effective contraception during the treatment period and for at least 12 months (for participants who received cyclophosphamide) or 6 months (for participants who did not receive cyclophosphamide) after the last dose of study treatment with pembrolizumab or placebo.
* Has adequate organ function.

Exclusion Criteria:

* Has a history of non-infectious pneumonitis that required treatment with steroids or has current pneumonitis.
* Has breast cancer with lobular histology.
* Has bilateral invasive breast cancer.
* Has metastatic (Stage IV) breast cancer.
* Has multi-centric breast cancer (presence of more than 1 tumor in different quadrants of the breast).
* Has any of the following clinical lymph node staging per current American Joint Committee on Cancer (AJCC) staging criteria for breast cancer staging based on radiological and/or clinical assessment: cN3, cN3a, cN3b, or cN3c.
* Has ER-, progesterone receptor positive breast cancer.
* Has undergone excisional biopsy of the primary tumor and/or axillary lymph nodes or has undergone sentinel lymph node biopsy prior to study treatment.
* Has a known additional, invasive, malignancy that is progressing or required active treatment in the last 5 years.

Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, ductal breast carcinoma in situ, or cervical carcinoma in situ that has undergone potentially curative therapy are not excluded.

* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
* Has an 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) Note: Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
* Has a known history of active tuberculosis (Bacillus tuberculosis).
* Has an active infection requiring systemic therapy.
* Has left ventricular ejection fraction (LVEF) of \<50% or below the institution limit of normal, as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed at screening.
* Has other significant cardiac disease, such as: 1) History of myocardial infarction, acute coronary syndrome, or coronary angioplasty/stenting/bypass within the last 6 months. or 2) Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA Class III or IV.
* Has a known history of human immunodeficiency virus (HIV) infection.
* Has a known history of hepatitis B or known active hepatitis C virus infection.
* Has received prior treatment for breast cancer.
* Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\], OX 40, CD137).
* Has received a live vaccine within 30 days prior to the first dose of study treatment.
* Has severe hypersensitivity (≥Grade 3) to any of the components or excipients used in the study treatments.
* Is/was enrolled in a study of an investigational agent and received study therapy, or used an investigational device within 4 weeks (12 months for an investigational agent or device with anticancer or antiproliferative properties) prior to the first dose of study treatment.
* Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 12 months (for participants who received cyclophosphamide) or 6 months (for participants who did not receive cyclophosphamide) after the last dose of study treatment.

Primary outcomes:
measure: Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0
timeFrame: Up to approximately 7 months (Time of surgery)
measure: Event-Free Survival (EFS)
timeFrame: Up to approximately 12 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 12 years
measure: pCR Rate Using the Definition of ypT0ypN0
timeFrame: Up to approximately 7 months (Time of surgery)
measure: pCR Rate Using the Definition of ypT0/Tis
timeFrame: Up to approximately 7 months (Time of surgery)
measure: pCR Rate Using the Definitions of ypT0/Tis ypN0, ypT0/Tis, and ypT0 ypN0 in Participants With a Combined Positive Score [CPS] ≥1
timeFrame: Up to approximately 7 months (Time of surgery)
measure: EFS in Participants With a CPS ≥1
timeFrame: Up to approximately 12 years
measure: OS in Participants With a CPS ≥1
timeFrame: Up to approximately 12 years
measure: Number of Participants Experiencing an Adverse Event (AE)
timeFrame: Up to approximately 15 months
measure: Number of Participants Experiencing a Serious Adverse Event (SAE)
timeFrame: Up to approximately 17 months
measure: Number of Participants Experiencing an Immune-related AE (irAE)
timeFrame: Up to approximately 15 months
measure: Number of Participants who Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 14 months
measure: Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire Core 30 (QLQ-C30) Score
timeFrame: Baseline (Cycle 1 Day 1 in Treatment 1) and Cycles 1 and 4 Day 1 in Treatment 2 (Up to approximately 5 months) Each cycle is 21 days.
measure: Change from Baseline in EORTC Breast Cancer-Specific QoL Questionnaire (QLQ-BR23) Score
timeFrame: Baseline (Cycle 1 Day 1 in Treatment 1) and Cycles 1 and 4 Day 1 in Treatment 2 (Up to approximately 5 months) Each cycle is 21 days.
Other outcomes:
Locations:
city: Daphne
country: United States
facility: Southern Cancer Center, PC ( Site 8003)
state: Alabama
city: Goodyear
country: United States
facility: Cancer Treatment Centers of America at Western Regional Medical Center ( Site 0001)
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates PC- HOPE ( Site 8008)
state: Arizona
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center Samuel Oschin Comp. Cancer Institute ( Site 0079)
state: California
city: Mountain View
country: United States
facility: El Camino Hospital Cancer Center ( Site 0004)
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Center ( Site 0072)
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center ( Site 0073)
state: California
city: Aurora
country: United States
facility: University of Colorado, Anschutz Cancer Pavilion ( Site 0008)
state: Colorado
city: Jacksonville
country: United States
facility: Baptist MD Anderson Cancer Center ( Site 0014)
state: Florida
city: Newnan
country: United States
facility: Southeastern Regional Medical Center, Inc. ( Site 0075)
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago Medical Center ( Site 0080)
state: Illinois
city: Skokie
country: United States
facility: Orchard Healthcare Research Inc. ( Site 0020)
state: Illinois
city: Zion
country: United States
facility: Midwestern Regional Medical Center, Inc. ( Site 0077)
state: Illinois
city: Goshen
country: United States
facility: Goshen Center for Cancer Care ( Site 0021)
state: Indiana
city: Waterloo
country: United States
facility: MercyOne Waterloo Cancer Center ( Site 0016)
state: Iowa
city: Louisville
country: United States
facility: James Graham Brown Cancer Center ( Site 0022)
state: Kentucky
city: Bethesda
country: United States
facility: Maryland Oncology Hematology, P.A. ( Site 8007)
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital ( Site 0024)
state: Massachusetts
city: Danvers
country: United States
facility: MGH - North Shore Cancer Center ( Site 0081)
state: Massachusetts
city: Newton
country: United States
facility: MGH Newton-Wellesley Hospital's Vernon Cancer Center ( Site 0082)
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System ( Site 0028)
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic and Medical School (Rochester) ( Site 0029)
state: Minnesota
city: Billings
country: United States
facility: St. Vincent Frontier Cancer Center ( Site 0033)
state: Montana
city: Omaha
country: United States
facility: Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0039)
state: Nebraska
city: Teaneck
country: United States
facility: Holy Name Medical Center ( Site 0041)
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medical College ( Site 0043)
state: New York
city: Tulsa
country: United States
facility: CTCA Southwestern ( Site 0074)
state: Oklahoma
city: Portland
country: United States
facility: OHSU Knight Cancer Institute ( Site 0051)
state: Oregon
city: Tigard
country: United States
facility: Northwest Cancer Specialists, P.C. ( Site 8000)
state: Oregon
city: Danville
country: United States
facility: Geisinger Medical Center ( Site 0052)
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center ( Site 0078)
state: Pennsylvania
city: Philadelphia
country: United States
facility: Cancer Treatment Centers of America-Eastern Regional Medical Center ( Site 0076)
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina ( Site 0053)
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC/The Sarah Cannon Research Institute ( Site 7000)
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology-Austin Central ( Site 8004)
state: Texas
city: Dallas
country: United States
facility: Texas Oncology-Dallas Presbyterian Hospital ( Site 8002)
state: Texas
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 8009)
state: Texas
city: Houston
country: United States
facility: Texas Oncology-Memorial City ( Site 8012)
state: Texas
city: Houston
country: United States
facility: University of Texas-MD Anderson Cancer Center ( Site 0083)
state: Texas
city: Plano
country: United States
facility: Texas Oncology- Plano East ( Site 8010)
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Northeast Texas ( Site 8006)
state: Texas
city: Midlothian
country: United States
facility: Bon Secours St. Francis Medical Center Oncology Research ( Site 0064)
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates ( Site 8001)
state: Virginia
city: Kennewick
country: United States
facility: Kadlec Clinic Hematology and Oncology ( Site 0070)
state: Washington
city: Spokane
country: United States
facility: Medical Oncology Associates (Summit Cancer Centers) ( Site 0066)
state: Washington
city: Camperdown
country: Australia
facility: Chris OBrien Lifehouse ( Site 2107)
state: New South Wales
city: Sydney
country: Australia
facility: Royal North Shore Hospital ( Site 2100)
state: New South Wales
city: Sydney
country: Australia
facility: Westmead Hospital ( Site 2101)
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Misericordiae Ltd ( Site 2106)
state: Queensland
city: Frankston
country: Australia
facility: Frankston Hospital ( Site 2103)
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre ( Site 2102)
state: Victoria
city: Bonheiden
country: Belgium
facility: Imelda Ziekenhuis Bonheiden ( Site 0703)
state: Antwerpen
city: Edegem
country: Belgium
facility: UZ Antwerpen - Medical Oncology ( Site 0709)
state: Antwerpen
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet ( Site 0710)
state: Bruxelles-Capitale, Region De
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc ( Site 0701)
state: Bruxelles-Capitale, Region De
city: Liège
country: Belgium
facility: CHC MontLegia ( Site 0707)
state: Liege
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis Campus Virga Jesse ( Site 0704)
state: Limburg
city: Yvoir
country: Belgium
facility: CHU UCL Namur Site de Godinne ( Site 0706)
state: Namur
city: Gent
country: Belgium
facility: AZ Maria Middelares Gent ( Site 0700)
state: Oost-Vlaanderen
city: Leuven
country: Belgium
facility: UZ Leuven ( Site 0702)
state: Vlaams-Brabant
city: Kortrijk
country: Belgium
facility: AZ Groeninge ( Site 0705)
state: West-Vlaanderen
city: Goiania
country: Brazil
facility: Hospital Araujo Jorge Associacao de Combate ao Cancer de Goias ( Site 0205)
state: Goias
city: Ijui
country: Brazil
facility: ONCOSITE - Centro de Pesquisa Clinica em Oncologia ( Site 0206)
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Associacao Hospitalar Moinhos de Vento ( Site 0201)
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0202)
state: Rio Grande Do Sul
city: Florianopolis
country: Brazil
facility: CEPON - Centro de Pesquisas Oncologicas ( Site 0208)
state: Santa Catarina
city: Itajai
country: Brazil
facility: Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral ( Site 0207)
state: Santa Catarina
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Câncer - INCA-Pesquisa Clinica HC3 ( Site 0200)
city: Sao Paulo
country: Brazil
facility: Clinica de Pesquisas e Ctro de Estudos Onc. Ginecol. e Mamaria Ltda ( Site 0204)
city: Sao Paulo
country: Brazil
facility: Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 0210)
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0209)
city: Edmonton
country: Canada
facility: Cross Cancer Institute ( Site 0115)
state: Alberta
city: Vancouver
country: Canada
facility: BC Cancer-Vancouver Center ( Site 0116)
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre ( Site 0112)
state: Ontario
city: Greenfield Park
country: Canada
facility: CISSS de la Monteregie-Centre ( Site 0108)
state: Quebec
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont CIUSSS de l Est de L Ile de Montreal ( Site 0111)
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0114)
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital ( Site 0103)
state: Quebec
city: Trois-Rivières
country: Canada
facility: Centre Hospitalier Regional de Trois-Rivieres ( Site 0106)
state: Quebec
city: Quebec
country: Canada
facility: CHU de Quebec Universite Laval - Hopital du Saint-Sacrement ( Site 0101)
city: Heifei
country: China
facility: Anhui Provincial Hospital ( Site 3224)
state: Anhui
city: Shanghai
country: China
facility: Ruijin Hosp,Shanghai Jiao Tong University School of Medicine ( Site 3215)
state: Anhui
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences ( Site 3208)
state: Beijing
city: Fuzhou Fujian
country: China
facility: Fujian Medical University Union Hospital-1 Bingfanglou-Oncology ( Site 3207)
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University ( Site 3213)
state: Guangdong
city: Shijia Zhuang
country: China
facility: Fourth Hospital Of Hebei Medical University ( Site 3216)
state: Hebei
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital ( Site 3200)
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital ( Site 3212)
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital ( Site 3211)
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital ( Site 3214)
state: Hunan
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University ( Site 3203)
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University ( Site 3201)
state: Jilin
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center ( Site 3205)
state: Shanghai
city: XI An
country: China
facility: The First Affiliated Hospital of Xi an Jiaotong University ( Site 3220)
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital ( Site 3209)
state: Tianjin
city: Urumqi
country: China
facility: The Affiliated Cancer Hospital of Xinjiang Medical ( Site 3219)
state: Xinjiang
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital ( Site 3225)
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital ( Site 3210)
state: Zhejiang
city: Medellin
country: Colombia
facility: Fundacion Colombiana de Cancerología Clinica Vida ( Site 0405)
state: Antioquia
city: Medellin
country: Colombia
facility: Rodrigo Botero SAS ( Site 0407)
state: Antioquia
city: Barranquilla
country: Colombia
facility: Clinica de la Costa S.A.S. ( Site 0400)
state: Atlantico
city: Monteria
country: Colombia
facility: IMAT S.A.S ( Site 0401)
state: Cordoba
city: Bogota
country: Colombia
facility: Centro de Investigacion Clinica del Country ( Site 0402)
state: Distrito Capital De Bogota
city: Bogota
country: Colombia
facility: Fundacion Universitaria Sanitas ( Site 0403)
state: Distrito Capital De Bogota
city: Cali
country: Colombia
facility: Clínica Imbanaco S.A.S ( Site 0406)
state: Valle Del Cauca
city: Santa Ana
country: Costa Rica
facility: Hospital Metropolitano - Sede Lindora ( Site 4203)
state: San Jose
city: Caen
country: France
facility: Centre Francois Baclesse ( Site 0927)
state: Calvados
city: Dijon
country: France
facility: Centre Georges Francois Leclerc ( Site 0920)
state: Cote-d Or
city: Toulouse
country: France
facility: Institut Claudius Regaud IUCT Oncopole ( Site 0903)
state: Haute-Garonne
city: Saint-Cloud
country: France
facility: Institut Curie - Centre Rene Huguenin ( Site 0917)
state: Hauts-de-Seine
city: Montpellier
country: France
facility: Centre de Cancerologie du Grand Montpellier ( Site 0925)
state: Herault
city: Metz
country: France
facility: CHR-METZ-THIONVILLE - Hopital de Mercy ( Site 0919)
state: Moselle
city: Lille
country: France
facility: Centre Oscar Lambret ( Site 0911)
state: Nord-Pas-de-Calais
city: Avignon
country: France
facility: Institut Sainte Catherine ( Site 0916)
state: Provence-Alpes-Cote-d Azur
city: Clermont Ferrand Cedex
country: France
facility: Centre Jean Perrin ( Site 0909)
state: Puy-de-Dome
city: Le Mans
country: France
facility: Clinique Victor Hugo Le Mans ( Site 0906)
state: Sarthe
city: Villejuif
country: France
facility: Institut Gustave Roussy ( Site 0926)
state: Val-de-Marne
city: Paris
country: France
facility: Institut Curie ( Site 0900)
city: Paris
country: France
facility: Hopital Saint-Louis ( Site 0908)
city: Paris
country: France
facility: Hopital Tenon ( Site 0914)
city: Friedrichshafen
country: Germany
facility: Medizinische Management GmbH ( Site 1012)
state: Baden-Wurttemberg
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen ( Site 1001)
state: Bayern
city: Muenchen
country: Germany
facility: Klinikum der Universitaet Muenchen - Grosshadern ( Site 1000)
state: Bayern
city: Offenbach
country: Germany
facility: Sana Klinikum Offenbach GmbH ( Site 1002)
state: Hessen
city: Wiesbaden
country: Germany
facility: HELIOS Dr. Horst Schmidt Kliniken Wiesbaden ( Site 1004)
state: Hessen
city: Hannover
country: Germany
facility: MVZ Onko Medical GmbH Hannover ( Site 1013)
state: Niedersachsen
city: Bonn
country: Germany
facility: Gynaekologisches Zentrum ( Site 1003)
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Kliniken Essen Mitte Gmbh Evang. Huyssens Stiftung ( Site 1006)
state: Nordrhein-Westfalen
city: Paderborn.
country: Germany
facility: Frauenklinik St. Louise ( Site 1014)
state: Nordrhein-Westfalen
city: Saarbruecken
country: Germany
facility: Caritas Klinikum Saarbruecken St. Theresia ( Site 1009)
state: Saarland
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus ( Site 1008)
state: Sachsen
city: Nordhausen
country: Germany
facility: MVZ Nordhausen gGmbH - Praxis Dr. Grafe ( Site 1005)
state: Thuringen
city: Kecskemét
country: Hungary
facility: Bacs-Kiskun Varmegyei Oktatokorhaz-Onkoradiologiai Kozpont ( Site 2913)
state: Bacs-Kiskun
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai Kozpont ( Site 2905)
state: Baranya
city: Miskolc
country: Hungary
facility: Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi OktatoKorhaz ( Site 2904)
state: Borsod-Abauj-Zemplen
city: Budapest
country: Hungary
facility: Budapesti Szent Margit Korhaz ( Site 2901)
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet ( Site 2908)
city: Budapest
country: Hungary
facility: Budapesti Uzsoki Utcai Kórház-Onkoradiológiai Osztály ( Site 2902)
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont ( Site 2907)
city: Kaposvar
country: Hungary
facility: Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 2915)
city: Cork
country: Ireland
facility: Bon Secours Hospital ( Site 1554)
city: Dublin
country: Ireland
facility: St. James s Hospital ( Site 1553)
city: Afula
country: Israel
facility: HaEmek Medical Center ( Site 1712)
city: Ashdod
country: Israel
facility: Assuta Ashdod Public ( Site 1704)
city: Beer Sheva
country: Israel
facility: Soroka Medical Center ( Site 1701)
city: Haifa
country: Israel
facility: Rambam Health Care Campus-Oncology Division ( Site 1705)
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center ( Site 1708)
city: Jerusalem
country: Israel
facility: Hadassah Ein Karem - Sharett Institute of Oncology ( Site 1700)
city: Kfar-Saba
country: Israel
facility: Meir Medical Center ( Site 1710)
city: Nazareth
country: Israel
facility: Holy Family Hospital ( Site 1711)
city: Petah Tikva
country: Israel
facility: Rabin Medical Center ( Site 1702)
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center. ( Site 1707)
city: Rehovot
country: Israel
facility: Kaplan Medical Center ( Site 1703)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 1706)
city: Tel Aviv
country: Israel
facility: Assuta Medical Center ( Site 1709)
city: Nagoya
country: Japan
facility: Aichi Cancer Center ( Site 2601)
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East ( Site 2613)
state: Chiba
city: Sapporo
country: Japan
facility: National Hospital Organization Hokkaido Cancer Center ( Site 2607)
state: Hokkaido
city: Nishinomiya
country: Japan
facility: Hyogo Medical University Hospital ( Site 2600)
state: Hyogo
city: Sagamihara
country: Japan
facility: Kitasato University Hospital ( Site 2616)
state: Kanagawa
city: Kumamoto-shi
country: Japan
facility: Kumamoto University Hospital ( Site 2602)
state: Kumamoto
city: Hidaka
country: Japan
facility: Saitama Medical University International Medical Center ( Site 2606)
state: Saitama
city: Kitaadachi-gun
country: Japan
facility: Saitama Prefectural Cancer Center ( Site 2612)
state: Saitama
city: Suntogun
country: Japan
facility: Shizuoka Cancer Center ( Site 2611)
state: Shizuoka
city: Chiba
country: Japan
facility: Chiba Cancer Center ( Site 2605)
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital ( Site 2610)
city: Hiroshima
country: Japan
facility: Hiroshima City Hiroshima Citizens Hospital ( Site 2603)
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital ( Site 2614)
city: Tokyo
country: Japan
facility: Toranomon Hospital ( Site 2608)
city: Tokyo
country: Japan
facility: Cancer Institute Hospital of JFCR ( Site 2604)
city: Tokyo
country: Japan
facility: Showa Medical University Hospital ( Site 2615)
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center ( Site 2204)
state: Kyonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 2200)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System ( Site 2201)
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center ( Site 2202)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 2203)
city: Tauranga
country: New Zealand
facility: Tauranga Hospital ( Site 2302)
state: Bay Of Plenty
city: Christchurch
country: New Zealand
facility: Canterbury Regional Cancer & Blood Services ( Site 2303)
state: Canterbury
city: Wellington
country: New Zealand
facility: Capital & Coast District Health Board - Wellington Hospital ( Site 2301)
city: Wrocław
country: Poland
facility: Dolnoslaskie Centrum Onkologii. ( Site 1820)
state: Dolnoslaskie
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1800)
state: Kujawsko-pomorskie
city: Lodz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki ( Site 1821)
state: Lodzkie
city: Ostroleka
country: Poland
facility: Mazowiecki Szpital Specjalistyczny im. dr Jozefa Psarskiego ( Site 1814)
state: Mazowieckie
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie ( Site 1899)
state: Mazowieckie
city: Wieliszew
country: Poland
facility: Mazowiecki Szpital Onkologiczny ( Site 1803)
state: Mazowieckie
city: Bialystok
country: Poland
facility: Bialostockie Centrum Onkologii ( Site 1819)
state: Podlaskie
city: Gdansk
country: Poland
facility: Wojewodzkie Centrum Onkologii Copernicus ( Site 1817)
state: Pomorskie
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Sp. z o.o. ( Site 1818)
state: Pomorskie
city: Bielsko-Biala
country: Poland
facility: Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 1810)
state: Slaskie
city: Bytom
country: Poland
facility: Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu ( Site 1807)
state: Slaskie
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 1801)
state: Slaskie
city: Lisboa
country: Portugal
facility: Fundacao Champalimaud ( Site 2500)
state: Aveiro
city: Lisboa
country: Portugal
facility: Unidade Local de Saude de Santa Maria - Hospital de Santa Maria ( Site 2501)
city: Porto
country: Portugal
facility: Unidade Local de Saude de Santo António - Hospital Santo António ( Site 2503)
city: Porto
country: Portugal
facility: Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 2502)
city: San Juan
country: Puerto Rico
facility: UPR Comprehensive Cancer Center ( Site 6200)
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Clinical Oncological Dispensary ( Site 1901)
state: Arkhangel Skaya Oblast
city: Ufa
country: Russian Federation
facility: Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1909)
state: Baskortostan, Respublika
city: Saint Petersburg
country: Russian Federation
facility: Railway Hospital of OJSC ( Site 1913)
state: Sankt-Peterburg
city: Saint Petersburg
country: Russian Federation
facility: Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1900)
state: Sankt-Peterburg
city: Tomsk
country: Russian Federation
facility: Tomsk Scientific Research Institute of Oncology ( Site 1905)
state: Tomskaya Oblast
city: Hospitalet de Llobregat
country: Spain
facility: Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 1363)
state: Barcelona
city: A Coruna
country: Spain
facility: Hospital Teresa Herrera - Chuac ( Site 1358)
state: La Coruna
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon ( Site 1367)
state: Madrid, Comunidad De
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Quiron de Madrid ( Site 1351)
state: Madrid
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia ( Site 1355)
state: Valenciana, Comunitat
city: Barcelona
country: Spain
facility: Instituto Oncologico Baselga.Hospital Quiron. ( Site 1352)
city: Barcelona
country: Spain
facility: Hospital Vall D Hebron ( Site 1357)
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial de Barcelona ( Site 1353)
city: Jaen
country: Spain
facility: Complejo Hospitalario de Jaen ( Site 1364)
city: Madrid
country: Spain
facility: Hospital Beata María Ana-oncology ( Site 1370)
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos ( Site 1354)
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre ( Site 1356)
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio ( Site 1360)
city: Valencia
country: Spain
facility: Hospital General Arnau de Vilanova de Valencia ( Site 1369)
city: Taichung
country: Taiwan
facility: China Medical University Hospital ( Site 2401)
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital ( Site 2400)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital ( Site 2404)
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center ( Site 2403)
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital ( Site 2402)
city: Antonivka Village
country: Ukraine
facility: Communal nonprofit enterprise "Kherson Regional Oncology Dispensary" of Kherson Regional Council ( Site 2713)
state: Khersonska Oblast
city: Odesa
country: Ukraine
facility: MI Odesa Regional Clinical Hospital ( Site 2701)
state: Odeska Oblast
city: Zaporizhzhia
country: Ukraine
facility: Medical center of the Limited Liability Company Yulis ( Site 2720)
state: Zaporizka Oblast
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust ( Site 1503)
state: Bristol, City Of
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust ( Site 1504)
state: England
city: Colchester
country: United Kingdom
facility: Colchester General Hospital ( Site 1508)
state: Essex
city: London
country: United Kingdom
facility: Barts Health NHS Trust ( Site 1500)
state: London, City Of
city: London
country: United Kingdom
facility: Guy's Hospital ( Site 1501)
state: London, City Of
city: London
country: United Kingdom
facility: St. Georges University Hospital NHS Foundation Trust ( Site 1505)
state: London, City Of
city: Solihull
country: United Kingdom
facility: Birmingham & Solihull Heartlands Hospital NHS ( Site 1506)
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital ( Site 1502)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: