Clinical trial NCT03740165: Study of Chemotherapy With Pembrolizumab (MK-3475) Followed by Maintenance With Olaparib (MK-7339) for the First-Line Treatment of Women With BRCA Non-mutated Advanced Epithelial Ovarian Cancer (EOC) (MK-7339-001/KEYLYNK-001/ENGOT-ov43/GOG-3036)
Official title: A Randomized Phase 3, Double-Blind Study of Chemotherapy With or Without Pembrolizumab Followed by Maintenance With Olaparib or Placebo for the First-Line Treatment of BRCA Non-mutated Advanced Epithelial Ovarian Cancer (EOC) (KEYLYNK-001 / ENGOT-ov43 / GOG-3036)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Ovarian Cancer
Fallopian Tube Cancer
Peritoneal Neoplasms
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: European Network of Gynaecological Oncological Trial Groups (ENGOT)
name: Gynecologic Oncology Group
First posted: 2018-11-14
Enrollment: 1367
Sex: FEMALE
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 treatment with carboplatin/paclitaxel\* PLUS pembrolizumab (MK-3475) and maintenance olaparib (MK-7339) in women with epithelial ovarian cancer (EOC), fallopian tube cancer, or primary peritoneal cancer.

The primary study hypotheses are that the combination of pembrolizumab plus carboplatin/paclitaxel\* followed by continued pembrolizumab and maintenance olaparib is superior to carboplatin/paclitaxel alone with respect to Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in participants with programmed death-ligand 1 (PD-L1)-positive tumors (Combined Positive Score \[CPS\]≥10) and in all participants, and that the combination of pembrolizumab plus carboplatin/paclitaxel followed by continued pembrolizumab is superior to carboplatin/paclitaxel alone with respect to PFS per RECIST 1.1 in participants with PD-L1-positive tumors (CPS≥10) and in all participants.

Detailed description: Following a lead-in period during which all participants receive a single 3-week cycle of carboplatin/paclitaxel\*, participants will be randomly assigned in to one of three treatment arms:

* Pembrolizumab + Olaparib,
* Pembrolizumab + Placebo for Olaparib
* Placebo for Pembrolizumab + Placebo for Olaparib

  * At Investigator's discretion and prior to participant randomization, one of the following carboplatin/paclitaxel regimens is to be selected:

    1. up to 5 cycles of carboplatin Area Under the Curve (AUC)5 or AUC6 AND paclitaxel 175 mg/m\^2 on Day 1 of each 3-week cycle
    2. up to 5 cycles of carboplatin AUC5 or AUC6 on Day 1 of each 3-week cycle AND paclitaxel 80 mg/m\^2 on Days 1, 8 and 15 of each 3-week cycle; or
    3. up to 5 cycles of carboplatin AUC2 or AUC2.7 AND paclitaxel 60 mg/m\^2 on Days 1, 8 and 15 of each 3-week cycle.

Docetaxel may be considered for participants who experience either a severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel only after consultation with the Sponsor. The recommended dose as determined by the Scottish Gynaecological Cancer Trials Group is Docetaxel 75 mg/m\^2 Q3W plus carboplatin AUC 5 Q3W.

Eligibility criteria: Inclusion Criteria:

* Has histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) Stage III or Stage IV EOC (high-grade predominantly serous, endometrioid (any grade), carcinosarcoma, mixed mullerian with high-grade serous component, clear cell, or low-grade serous OC), primary peritoneal cancer, or fallopian tube cancer
* Has just completed primary debulking surgery or is eligible for primary debulking surgery or is a potential candidate for interval debulking surgery
* Is a candidate for carboplatin and paclitaxel chemotherapy, to be administered in the adjuvant or neoadjuvant setting
* Candidates for neoadjuvant chemotherapy, has a cancer antigen 125 (CA-125) (kilounits/L):carcinoembryonic antigen (CEA; ng/mL) ratio greater than or equal to 25
* Is able to provide a newly obtained core or excisional biopsy of a tumor lesion for prospective testing of BRCA1/2 and Programmed Cell Death-Ligand 1 (PD-L1) tumor markers status prior to randomization
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 7 days prior to initiating chemotherapy in the lead-in period and within 3 days prior to Day 1 of Cycle 1
* Female participants are not pregnant, not breastfeeding, and at least 1 of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) OR b.) Is a WOCBP and using a contraceptive method that is highly effective, with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle, during the Treatment Period and for at least 120 days following the last dose of pembrolizumab (or pembrolizumab placebo) and bevacizumab (if administered), at least 180 days following the last dose of olaparib (or olaparib placebo), and at least 210 days following the last dose of chemotherapy and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The investigator should evaluate the potential for contraceptive method failure in relationship to the first dose of study treatment. A WOCBP must have a negative highly sensitive pregnancy test within either 24 hours (urine) or 72 hours (serum) before the first dose of study treatment. If a urine test cannot be confirmed as negative, a serum pregnancy test is required. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
* Has adequate organ function

Exclusion Criteria:

* Has mucinous, germ cell, or borderline tumor of the ovary
* Has a known or suspected deleterious mutation (germline or somatic) in either BRCA1 or BRCA2
* Has a history of non-infectious pneumonitis that required treatment with steroids or currently has pneumonitis
* Has either myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of MDS/AML
* Has a known additional malignancy that is progressing or has required active treatment in the last 3 years Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. ductal carcinoma in situ, cervical carcinoma in situ) that has undergone potentially curative therapy are not excluded.
* Has ongoing Grade 3 or Grade 4 toxicity, excluding alopecia, following chemotherapy administered during the lead-in period
* Has known active central nervous system metastases and/or carcinomatous meningitis. Participants with brain metastases may participate provided they were previously treated (except with chemotherapy) and are radiologically stable, clinically stable, and no steroids were used for the management of symptoms related to brain metastases within 14 days prior to randomization. Stable brain metastases should be established prior to the first dose of study medication lead-in chemotherapy
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing \>10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization
* 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 and is allowed.
* Has a known history of active tuberculosis (TB; Bacillus Tuberculosis)
* Has an active infection requiring systemic therapy
* Has received colony-stimulating factors (eg, granulocyte colony stimulating factor \[G-CSF\], granulocyte macrophage colony-stimulating factor \[GM-CSF\] or recombinant erythropoietin) within 4 weeks prior to receiving chemotherapy during the lead-in period
* Is considered to be of poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection
* Has had surgery to treat borderline tumors, early stage EOC, or early stage fallopian tube cancer \<6 months prior to screening
* Has a known history of human immunodeficiency virus (HIV) infection
* Has a known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Testing for hepatitis B or hepatitis C is required at screening only if mandated by local health authority. Note: Participants with a history of hepatitis B but who are HBsAg negative are eligible for the study
* Is either unable to swallow orally administered medication or has a gastrointestinal (GI) disorder affecting absorption (e.g. gastrectomy, partial bowel obstruction, malabsorption)
* Has uncontrolled hypertension
* Has current, clinically relevant bowel obstruction (including sub-occlusive disease), abdominal fistula or GI perforation, related to underlying EOC (for participants receiving bevacizumab)
* Has a history of hemorrhage, hemoptysis or active GI bleeding within 6 months prior to randomization (for participants receiving bevacizumab)
* Is a WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of chemotherapy in the lead-in period and within 72 hours prior to Day 1 of Cycle 1, is pregnant or breastfeeding, or is expecting to conceive children within the projected duration of the study, starting with screening through 120 days following the last dose of pembrolizumab (or pembrolizumab placebo) and bevacizumab (if administered), at least 180 days following the last dose of olaparib (or olaparib placebo), and at least 210 days following the last dose of chemotherapy
* Has received prior treatment for any stage of OC, including radiation or systemic anti-cancer therapy (e.g. chemotherapy, hormonal therapy, immunotherapy, investigational therapy)
* Has received prior therapy with an anti-Programmed Cell Death-1 (anti-PD-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 antigen-4 \[CTLA-4\], OX 40, CD137)
* Has received prior therapy with either olaparib or any other poly(adenosine-ribose) polymerase (PARP) inhibitor
* Has intraperitoneal chemotherapy planned or has been administered as first-line therapy
* Has received a live vaccine within 30 days prior to the first dose of study treatment on Day 1 of Cycle 1
* Has severe hypersensitivity (≥Grade 3) to pembrolizumab, olaparib, carboplatin, paclitaxel or bevacizumab (if using) and/or any of their excipients
* Is currently receiving either strong (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (eg, ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study
* Is currently receiving either strong (e.g. phenobarbital, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine, and St John's Wort) or moderate (e.g. bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study
* Is currently participating or has participated in a study of an investigational agent or has used an investigational device within 4 weeks (28 days) of starting chemotherapy in the Lead-in Period
* Has resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions or participant has congenital long QT syndrome
* Has had an allogenic tissue/solid organ transplant, has received previous allogenic bone-marrow transplant, or has received double umbilical cord transplantation
* Either has had major surgery within 3 weeks of randomization or has not recovered from any effects of any major surgery

Primary outcomes:
measure: Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator in Participants with Programmed Death-Ligand 1 (PD-L1)-Positive Tumors (Combined Positive Score [CPS]≥10)
timeFrame: Up to approximately 57 months
measure: PFS Per RECIST 1.1 as Assessed by the Investigator in All Participants
timeFrame: Up to approximately 57 months
Secondary outcomes:
measure: Overall Survival (OS) in All Participants
timeFrame: Up to approximately 6 years
measure: OS in Participants with PDL-1 Positive Tumors (CPS ≥ 10)
timeFrame: Up to approximately 6 years
measure: PFS Per RECIST 1.1 as Assessed by Blinded Independent Central Review (BICR) in Participants with PD-L1-Positive Tumors (CPS≥10)
timeFrame: Up to approximately 57 months
measure: PFS Per RECIST 1.1 as Assessed by BICR in All Participants
timeFrame: Up to approximately 57 months
measure: PFS After Second-line Treatment (PFS2) Following Discontinuation of Study Treatment as Assessed by the Investigator in Participants with PD-L1-Positive Tumors (CPS≥10)
timeFrame: Up to approximately 78 months
measure: PFS2 Following Discontinuation of Study Treatment as Assessed by the Investigator in All Participants
timeFrame: Up to approximately 78 months
measure: Number of Participants Who Experience an Adverse Event (AE)
timeFrame: Up to approximately 73 months
measure: Number of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 6 years
measure: Mean Change from Baseline in Global Health Status/Quality of Life (GHS/QoL) Score Using Questions from the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30)
timeFrame: Baseline and End of Study Participation (Up to approximately 6 years)
measure: Mean Change from Baseline in Abdominal and Gastrointestinal (Abdominal/GI) Symptoms Score Using the EORTC Quality of Life Questionnaire-Ovarian Cancer (QLQ-OV28) Abdominal/GI Symptom Scale
timeFrame: Baseline and End of Study Participation (Up to approximately 6 years)
measure: Time to deterioration (TTD) of GHS/QoL score using EORTC QLQ-C30
timeFrame: Up to approximately 6 years
measure: Time to deterioration (TTD) of abdominal/GI symptoms using EORTC QLQ-OV28
timeFrame: Up to approximately 6 years
measure: Time to First Subsequent Anti-cancer Treatment (TFST)
timeFrame: Up to approximately 6 years
measure: Time to Second Subsequent Anti-cancer Treatment (TSST)
timeFrame: Up to approximately 6 years
measure: Time to Discontinuation of Study Treatment or Death (TDT)
timeFrame: Up to approximately 6 years
measure: Pathological Complete Response (pCR) Rate
timeFrame: Up to approximately 30 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham (UAB) ( Site 0036)
state: Alabama
city: Tucson
country: United States
facility: University of Arizona Cancer Center ( Site 0074)
state: Arizona
city: Burbank
country: United States
facility: Disney Family Cancer Center ( Site 0042)
state: California
city: Oakland
country: United States
facility: Kaiser Permanente Oncology Clinical Trial -Oakland ( Site 0077)
state: California
city: Roseville
country: United States
facility: Kaiser Permanente Oncology Clinical Trials-Roseville ( Site 0084)
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Oncology Clinical Trials-Sacramento ( Site 0083)
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente Oncology Clinical Trial - San Francisco ( Site 0078)
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente Oncology Clinical Trial - Santa Clara ( Site 0079)
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente N. CA Regional Oncology Clinical Trials ( Site 0008)
state: California
city: Walnut Creek
country: United States
facility: Kaiser Permanente Oncology Clinical Trial - Walnut Creek ( Site 0080)
state: California
city: New Haven
country: United States
facility: Smilow Cancer Center at Yale-New Haven ( Site 0057)
state: Connecticut
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital ( Site 0023)
state: Florida
city: Atlanta
country: United States
facility: Emory School of Medicine ( Site 0053)
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center ( Site 0029)
state: Georgia
city: Savannah
country: United States
facility: Memorial Health University Medical Center ( Site 0011)
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center ( Site 0019)
state: Illinois
city: Chicago
country: United States
facility: University of Chicago ( Site 0049)
state: Illinois
city: Hinsdale
country: United States
facility: Dr. Sudarshan K. Sharma, LTD ( Site 0061)
state: Illinois
city: Indianapolis
country: United States
facility: Saint Vincent Hospital and Health Center ( Site 0012)
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics ( Site 0005)
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky ( Site 0045)
state: Kentucky
city: Baltimore
country: United States
facility: Weinberg Cancer Institute at Franklin Square ( Site 0035)
state: Maryland
city: Jackson
country: United States
facility: Saint Dominic - Jackson Memorial Hospital ( Site 0072)
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University - School of Medicine ( Site 0062)
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital ( Site 0063)
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center ( Site 0024)
state: New Hampshire
city: Camden
country: United States
facility: MD Anderson Cancer Center at Cooper ( Site 0067)
state: New Jersey
city: Teaneck
country: United States
facility: Holy Name Medical Center ( Site 0037)
state: New Jersey
city: Lake Success
country: United States
facility: Northwell Health- Monter Cancer Center ( Site 0075)
state: New York
city: Fargo
country: United States
facility: Sanford Roger Maris Cancer Center ( Site 0082)
state: North Dakota
city: Centerville
country: United States
facility: Miami Valley Hospital [Dayton, OH] ( Site 0073)
state: Ohio
city: Cincinnati
country: United States
facility: Oncology/Hematology Care Clinical Trials, LLC ( Site 8001)
state: Ohio
city: Columbus
country: United States
facility: The Bing Cancer Center ( Site 0044)
state: Ohio
city: Hilliard
country: United States
facility: OSU Wexner Medical Center ( Site 0076)
state: Ohio
city: Providence
country: United States
facility: Women and Infants Hospital [Providence, RI] ( Site 0039)
state: Rhode Island
city: Sioux Falls
country: United States
facility: Sanford Gynecology Oncology ( Site 0004)
state: South Dakota
city: Bedford
country: United States
facility: Texas Oncology, P.A. - Bedford ( Site 8005)
state: Texas
city: Dallas
country: United States
facility: Texas Oncology-Dallas Presbyterian Hospital ( Site 8004)
state: Texas
city: Dallas
country: United States
facility: Parkland Hospital ( Site 0081)
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center ( Site 0046)
state: Texas
city: Tyler
country: United States
facility: Texas Oncology, P.A. Texas Oncology-Tyler ( Site 8006)
state: Texas
city: Gainesville
country: United States
facility: Virginia Cancer Specialists, PC ( Site 8003)
state: Virginia
city: Milwaukee
country: United States
facility: MEDICAL COLLEGE OF WISCONSIN ( Site 0064)
state: Wisconsin
city: Kogarah
country: Australia
facility: St George Hospital ( Site 2207)
state: New South Wales
city: Cairns
country: Australia
facility: Cairns and Hinterland Hospital and Health Service ( Site 2201)
state: Queensland
city: Ballarat
country: Australia
facility: Ballarat Health Services ( Site 2202)
state: Victoria
city: Clayton
country: Australia
facility: Monash Health ( Site 2204)
state: Victoria
city: St Albans
country: Australia
facility: Sunshine Hospital. ( Site 2205)
state: Victoria
city: Bonheiden
country: Belgium
facility: Imelda Ziekenhuis Bonheiden ( Site 0301)
state: Antwerpen
city: Leuven
country: Belgium
facility: UZ Leuven Campus Gasthuisberg ( Site 0306)
state: Antwerpen
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc ( Site 0312)
state: Bruxelles-Capitale, Region De
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi ( Site 0302)
state: Hainaut
city: Liège
country: Belgium
facility: CHU de Liege ( Site 0310)
state: Liege
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis ( Site 0309)
state: Limburg
city: Libramont
country: Belgium
facility: Centre Hospitalier de l'Ardenne ( Site 0303)
state: Luxembourg
city: Gent
country: Belgium
facility: AZ Maria Middelares Gent ( Site 0300)
state: Oost-Vlaanderen
city: Gent
country: Belgium
facility: UZ Gent ( Site 0307)
state: Oost-Vlaanderen
city: Fortaleza
country: Brazil
facility: Instituto do Cancer do Ceara ( Site 2707)
state: Ceara
city: Goiania
country: Brazil
facility: Hospital Araujo Jorge Associacao de Combate ao Cancer de Goias ( Site 2708)
state: Goias
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner ( Site 2716)
state: Parana
city: Ijui
country: Brazil
facility: Hospital de Caridade de Ijui ( Site 2712)
state: Rio Grande Do Sul
city: Lajeado
country: Brazil
facility: Hospital Bruno Born ( Site 2704)
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora Da Conceicao ( Site 2703)
state: Rio Grande Do Sul
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Cancer Hospital do Cancer II ( Site 2700)
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 2714)
city: Sao Paulo
country: Brazil
facility: Clinica de Pesquisas e Ctro de Estudos Onc. Ginecol. e Mamaria Ltda ( Site 2706)
city: Sao Paulo
country: Brazil
facility: Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 2710)
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre ( Site 0200)
state: Alberta
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre ( Site 0207)
state: Ontario
city: Mississauga
country: Canada
facility: The Credit Valley Hospital ( Site 0206)
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital.. ( Site 0202)
state: Ontario
city: Chicoutimi
country: Canada
facility: CIUSSS du Saguenay-Lac-St-Jean ( Site 0218)
state: Quebec
city: Montreal
country: Canada
facility: CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0219)
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0208)
state: Quebec
city: Montreal
country: Canada
facility: Royal Victoria Hospital McGill University Health Centre ( Site 0211)
state: Quebec
city: Temuco
country: Chile
facility: Centro Investigación del Cáncer James Lind ( Site 2810)
state: Araucania
city: Temuco
country: Chile
facility: Centro de Investigacion y desarrollo Oncologico SpA - CIDO SpA ( Site 2808)
state: Araucania
city: Santiago
country: Chile
facility: Fundacion Arturo Lopez Perez FALP ( Site 2800)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Sociedad Oncovida S.A. ( Site 2807)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Iram Cancer Research ( Site 2809)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Pontificia Universidad Catolica de Chile ( Site 2805)
state: Region M. De Santiago
city: Vina del Mar
country: Chile
facility: Oncocentro ( Site 2801)
state: Valparaiso
city: Antofagasta
country: Chile
facility: Centro Oncologico Antofagasta ( Site 2804)
city: Barranquilla
country: Colombia
facility: Biomelab S A S ( Site 2900)
state: Atlantico
city: Valledupar
country: Colombia
facility: Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 2913)
state: Cesar
city: Monteria
country: Colombia
facility: Oncomedica S.A. ( Site 2911)
state: Cordoba
city: Bogota
country: Colombia
facility: Instituto Nacional de Cancerologia E.S.E ( Site 2910)
state: Distrito Capital De Bogota
city: Bogota
country: Colombia
facility: Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 2912)
state: Distrito Capital De Bogota
city: Cali
country: Colombia
facility: Centro Medico Imbanaco de Cali S.A ( Site 2909)
state: Valle Del Cauca
city: Cali
country: Colombia
facility: Hemato Oncologos S.A. ( Site 2906)
state: Valle Del Cauca
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno ( Site 0404)
state: Brno-mesto
city: Ostrava-Poruba
country: Czechia
facility: Fakultni nemocnice Ostrava ( Site 0403)
state: Moravskoslezsky Kraj
city: Praha
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze ( Site 0400)
state: Praha, Hlavni Mesto
city: Praha
country: Czechia
facility: Nemocnice Na Bulovce ( Site 0401)
state: Praha, Hlavni Mesto
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc ( Site 0402)
city: Lyon
country: France
facility: Hopital Prive Jean Mermoz ( Site 0607)
state: Auvergne
city: Strasbourg
country: France
facility: Centre Paul Strauss ( Site 0615)
state: Bas-Rhin
city: Marseille
country: France
facility: Hopital de la Timone ( Site 0617)
state: Bouches-du-Rhone
city: Brest
country: France
facility: CHU de Brest -Site Hopital Morvan ( Site 0616)
state: Bretagne
city: Nimes
country: France
facility: Institut de Cancerologie du Gard - CHU Caremeau ( Site 0610)
state: Gard
city: Saint-Priest-en-Jarez
country: France
facility: Institut de Cancerologie Lucien Neuwirth ( Site 0613)
state: Loire
city: Nancy
country: France
facility: Centre D Oncologie de Gentilly ( Site 0609)
state: Meurthe-et-Moselle
city: Villejuif
country: France
facility: Institut Gustave Roussy ( Site 0600)
state: Val-de-Marne
city: Paris
country: France
facility: Hopital Tenon ( Site 0612)
city: Stuttgart
country: Germany
facility: Marienhospital Stuttgart Vincenz von Paul Kliniken gGmbH ( Site 0707)
state: Baden-Wurttemberg
city: Muenchen
country: Germany
facility: Klinikum Rechts der Isar. Technischen Universitaet Muenchen ( Site 0710)
state: Bayern
city: Aachen
country: Germany
facility: Uniklinik RWTH Aachen ( Site 0718)
state: Nordrhein-Westfalen
city: Bonn
country: Germany
facility: Gynaekologisches Zentrum ( Site 0712)
state: Nordrhein-Westfalen
city: Dortmund
country: Germany
facility: Klinikum Dortmund gGmbH ( Site 0717)
state: Nordrhein-Westfalen
city: Duesseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf ( Site 0704)
state: Nordrhein-Westfalen
city: Krefeld
country: Germany
facility: HELIOS Klinikum Krefeld ( Site 0715)
state: Nordrhein-Westfalen
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster ( Site 0720)
state: Nordrhein-Westfalen
city: Saarbruecken
country: Germany
facility: Caritas Klinikum Saarbruecken St. Theresia ( Site 0702)
state: Saarland
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH ( Site 0711)
state: Sachsen
city: Kiel
country: Germany
facility: Staedtisches Krankenhaus Kiel GmbH ( Site 0709)
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Charite Campus Virchow-Klinikum - CVK ( Site 0700)
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai Kozpont ( Site 0805)
state: Baranya
city: Miskolc
country: Hungary
facility: Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz ( Site 0802)
state: Borsod-Abauj-Zemplen
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet ( Site 0800)
city: Budapest
country: Hungary
facility: Uzsoki Utcai Korhaz ( Site 0803)
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont ( Site 0801)
city: Beer-Sheva
country: Israel
facility: Soroka Medical Center ( Site 1006)
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center ( Site 1011)
city: Haifa
country: Israel
facility: Carmel Medical Center ( Site 1007)
city: Haifa
country: Israel
facility: Rambam Medical Center ( Site 1002)
city: Holon
country: Israel
facility: Edith Wolfson Medical Center ( Site 1003)
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center ( Site 1005)
city: Petah Tikva
country: Israel
facility: Rabin Medical Center ( Site 1004)
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center ( Site 1000)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 1001)
city: Bari
country: Italy
facility: IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 1108)
state: Abruzzo
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia ( Site 1100)
state: Lombardia
city: Torino
country: Italy
facility: A.O.U. Citta della Salute e della Scienza di Torino ( Site 1104)
state: Piemonte
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS ( Site 1113)
state: Veneto
city: Benevento
country: Italy
facility: Sacro Cuore di Gesu Fatebenefratelli ( Site 1112)
city: Catania
country: Italy
facility: Ospedale Cannizzaro ( Site 1110)
city: Lecco
country: Italy
facility: ASST Lecco. Ospedale A. Manzoni ( Site 1101)
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 1115)
city: Napoli
country: Italy
facility: A.O.U. Federico II di Napoli ( Site 1107)
city: Roma
country: Italy
facility: Azienda Ospedaliera Policlinico Umberto I ( Site 1111)
city: Roma
country: Italy
facility: Policlinico Universitario Gemelli ( Site 1105)
city: Trento
country: Italy
facility: Presidio Ospedaliero Santa Chiara ( Site 1109)
city: Udine
country: Italy
facility: A.O. Univ. S. M. della Misericordia ( Site 1114)
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East ( Site 2602)
state: Chiba
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center ( Site 2601)
state: Ehime
city: Toon
country: Japan
facility: Ehime University Hospital ( Site 2600)
state: Ehime
city: Ota
country: Japan
facility: Gunma Prefectural Cancer Center ( Site 2609)
state: Gunma
city: Sapporo
country: Japan
facility: Hokkaido University Hospital ( Site 2607)
state: Hokkaido
city: Shiwa-gun
country: Japan
facility: Iwate Medical University Hospital ( Site 2606)
state: Iwate
city: Kawasaki
country: Japan
facility: St. Marianna University School of Medicine Hospital ( Site 2613)
state: Kanagawa
city: Nakagami-gun
country: Japan
facility: University of the Ryukyus Hospital ( Site 2616)
state: Okinawa
city: Hidaka
country: Japan
facility: Saitama Medical University International Medical Center ( Site 2604)
state: Saitama
city: Kitaadachi-gun
country: Japan
facility: Saitama Cancer Center ( Site 2614)
state: Saitama
city: Tokorozawa
country: Japan
facility: National Defense Medical College Hospital ( Site 2608)
state: Saitama
city: Mitaka
country: Japan
facility: Kyorin University Hospital ( Site 2610)
state: Tokyo
city: Kagoshima
country: Japan
facility: Kagoshima City Hospital ( Site 2612)
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital ( Site 2618)
city: Osaka
country: Japan
facility: Osaka International Cancer Institute ( Site 2617)
city: Tokyo
country: Japan
facility: National Cancer Center Hospital ( Site 2605)
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital ( Site 2404)
state: Kyonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 2403)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System ( Site 2400)
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center ( Site 2402)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 2401)
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
state: Mazowieckie
city: Bialystok
country: Poland
facility: Bialostockie Centrum Onkologii ( Site 1412)
state: Podlaskie
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Sp. z o.o. ( Site 1407)
state: Pomorskie
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 1406)
state: Slaskie
city: Kielce
country: Poland
facility: Swietokrzyskie Centrum Onkologii SPZOZ ( Site 1410)
state: Swietokrzyskie
city: Poznan
country: Poland
facility: Szpital Kliniczny im. Przemienienia Panskiego Uniwersytetu Medycznego im. K. Marcinkowskiego w Pozna
state: Wielkopolskie
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Clinical Oncological Dispensary ( Site 1508)
state: Arkhangel Skaya Oblast
city: Ufa
country: Russian Federation
facility: Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1507)
state: Baskortostan, Respublika
city: Obninsk
country: Russian Federation
facility: A. Tsyb Medical Radiological Research Center ( Site 1513)
state: Kaluzskaja Oblast
city: Moscow
country: Russian Federation
facility: FSBI National Medical Oncology Research Center n.a. N.N. Blokhina ( Site 1500)
state: Moskva
city: Moscow
country: Russian Federation
facility: FSCC of Special Types of Med. Care and Technologies ( Site 1503)
state: Moskva
city: Moscow
country: Russian Federation
facility: Medical Rehabilitation Center ( Site 1502)
state: Moskva
city: Saint Petersburg
country: Russian Federation
facility: City Clinical Oncology Center ( Site 1505)
state: Sankt-Peterburg
city: Saint-Petersburg
country: Russian Federation
facility: National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 1504)
state: Sankt-Peterburg
city: Kazan
country: Russian Federation
facility: Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1509)
state: Tatarstan, Respublika
city: Port Elizabeth
country: South Africa
facility: Cancer Care Langenhoven Drive Oncology Centre ( Site 1701)
state: Eastern Cape
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital ( Site 1704)
state: Gauteng
city: Johannesburg
country: South Africa
facility: Wits Clinical Research ( Site 1702)
state: Gauteng
city: Pretoria
country: South Africa
facility: Department of Medical Oncology ( Site 1703)
state: Gauteng
city: Pretoria
country: South Africa
facility: Curo Oncology ( Site 1710)
state: Gauteng
city: Pretoria
country: South Africa
facility: Wilgers Oncology Centre ( Site 1705)
state: Gauteng
city: Pretoria
country: South Africa
facility: Little Company of Mary Hospital ( Site 1700)
state: Gauteng
city: Sandton
country: South Africa
facility: Sandton Oncology Medical Group PTY LTD ( Site 1712)
state: Gauteng
city: Durban
country: South Africa
facility: The Oncology Centre ( Site 1709)
state: Kwazulu-Natal
city: Cape Town
country: South Africa
facility: Cancercare ( Site 1706)
state: Western Cape
city: George
country: South Africa
facility: Outeniqua Cancercare Oncology Unit ( Site 1708)
state: Western Cape
city: Kraaifontein
country: South Africa
facility: Cape Town Oncology Trials Pty Ltd ( Site 1707)
state: Western Cape
city: Hospitalet de Llobregat
country: Spain
facility: Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 1603)
state: Barcelona
city: Manresa
country: Spain
facility: Xarxa Assistencial Universitaria Manresa ( Site 1605)
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital de Terrassa ( Site 1606)
state: Barcelona
city: Donostia
country: Spain
facility: Hospital Universitario de Donostia ( Site 1602)
state: Gipuzkoa
city: A Coruna
country: Spain
facility: Complejo Hospitalario Universitario A Coruna. CHUAC ( Site 1608)
state: La Coruna
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia ( Site 1601)
state: Valenciana, Comunitat
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia ( Site 1610)
state: Valenciana, Comunitat
city: Caceres
country: Spain
facility: Hospital Provincial San Pedro de Alcantara ( Site 1607)
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti ( Site 1609)
city: Madrid
country: Spain
facility: Clinica Universitaria de Navarra ( Site 1600)
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio ( Site 1604)
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital ( Site 2507)
city: Taichung
country: Taiwan
facility: China Medical University Hospital ( Site 2506)
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital ( Site 2510)
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital ( Site 2508)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital ( Site 2502)
city: Taipei
country: Taiwan
facility: MacKay Memorial Hospital ( Site 2500)
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital ( Site 2503)
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital ( Site 2501)
city: Kucukcekmece
country: Turkey
facility: Istanbul Acibadem University Atakent Hospital ( Site 1902)
state: Istanbul
city: Ankara
country: Turkey
facility: Etlik Zubeyde Hanim Kadin Hastaliklari Egitim ve Arastirma Hastanesi ( Site 1903)
city: Ankara
country: Turkey
facility: Ankara UTF Cebeci Arastırma ve Uygulama Hastanesi ( Site 1905)
city: Antalya
country: Turkey
facility: Akdeniz Universitesi Tıp Fakultesi ( Site 1901)
city: Bursa
country: Turkey
facility: Uludag Universitesi Tip Fakultesi ( Site 1904)
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Istanbul Tip Fakultesi ( Site 1900)
city: Istanbul
country: Turkey
facility: Bakirkoy Sadi Konuk Egitim ve Arastirma Hastanesi ( Site 1907)
city: Istanbul
country: Turkey
facility: Medipol Universite Hastanesi ( Site 1909)
city: Sakarya
country: Turkey
facility: Sakarya Universitesi Tip Fakultesi Hastanesi ( Site 1906)
city: Ivano-Frankivsk
country: Ukraine
facility: MI Precarpathian Clinical Oncology Center ( Site 2181)
state: Ivano-Frankivska Oblast
city: Kharkiv
country: Ukraine
facility: Grigoriev Institute for medical Radiology NAMS of Ukraine ( Site 2180)
state: Kharkivska Oblast
city: Khmelnytskyi
country: Ukraine
facility: Municipal non-profit Enterprise Khmelnytskyi Regional Antitu-Gynecological Oncology department, Poli
state: Khmelnytska Oblast
city: Lviv
country: Ukraine
facility: Lviv State Oncology Regional Treatment and Diagnostic Center ( Site 2170)
state: Lvivska Oblast
city: Odesa
country: Ukraine
facility: MI Odessa Regional Oncological Centre ( Site 2121)
state: Odeska Oblast
city: Sumy
country: Ukraine
facility: RMI - Sumy Regional Clinical Oncology Dispensary ( Site 2191)
state: Sumska Oblast
city: Uzhgorod
country: Ukraine
facility: Central City Clinical Hospital ( Site 2150)
state: Zakarpatska Oblast
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Oncological Center ( Site 2140)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: