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)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pembrolizumab+Chemotherapy (KX/KA[E]C) In the neoadjuvant setting, participants receive pembrolizumab (K) 200 mg via intravenous (IV) infusion once every 3 weeks (Q3W) + paclitaxel (X) 80 mg/m^2 via IV infusion once weekly (QW) for 4 cycles (Treatment 1), followed by pembrolizumab 200 mg via IV infusion + doxorubicin or epirubicin (A or E; 60 mg/m^2 or 100 mg/m^2) via IV infusion either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo surgery for their breast cancer. After surgery, participants will begin adjuvant study treatment. In the adjuvant setting, participants receive pembrolizumab 200 mg via IV infusion Q3W for 9 cycles + variable endocrine therapy for up to 10 years. Each cycle is 21 days long. |
Biological: Pembrolizumab (K)
IV infusion Q3W
Other Names:
Drug: Paclitaxel (X)
IV infusion QW
Other Names:
Drug: Doxorubicin (A)
IV infusion either in Q2W or Q3W
Other Names:
Drug: Epirubicin (E)
IV infusion either in Q2W or Q3W
Other Names:
Drug: Cyclophosphamide (C)
IV infusion either in Q2W or Q3W
Other Names:
Drug: Endocrine therapy
Variable endocrine therapy for up 10 years
Radiation: Radiation therapy
Variable radiation therapy per local standard of care
Procedure: Surgery
Surgery for breast cancer
|
| Placebo Comparator: Placebo+Chemotherapy (PX/PA[E]C) In the neoadjuvant setting, participants receive placebo (P; normal saline or dextrose) via IV infusion Q3W + paclitaxel (X) 80 mg/m^2 via IV infusion once weekly (QW) for 4 cycles (Treatment 1), followed by placebo via IV infusion + doxorubicin or epirubicin (A or E; 60 mg/m^2 or 100 mg/m^2) via IV infusion either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo surgery for their breast cancer. After surgery, participants will begin adjuvant study treatment. In the adjuvant setting, participants receive placebo via IV infusion Q3W for 9 cycles + variable endocrine therapy for up to 10 years. Each cycle is 21 days long. |
Drug: Placebo (P)
Normal saline or dextrose IV infusion Q3W
Drug: Paclitaxel (X)
IV infusion QW
Other Names:
Drug: Doxorubicin (A)
IV infusion either in Q2W or Q3W
Other Names:
Drug: Epirubicin (E)
IV infusion either in Q2W or Q3W
Other Names:
Drug: Cyclophosphamide (C)
IV infusion either in Q2W or Q3W
Other Names:
Radiation: Radiation therapy
Variable radiation therapy per local standard of care
Procedure: Surgery
Surgery for breast cancer
|
Outcome Measures
Primary Outcome Measures
- Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0 [Up to approximately 7 months (Time of surgery)]
The pCR rate (ypT0/Tis ypN0) is defined as the percentage of participants without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by American Joint Committee on Cancer (AJCC) staging criteria (8th edition) assessed by the local pathologist at the time of surgery. The percentage of participants with a pathological Complete Response (pCR) using the definition of (ypT0/Tis ypN0) will be presented for pembrolizumab versus placebo, both in combination with the protocol-specified neoadjuvant anticancer therapies.
- Event-Free Survival (EFS) [Up to approximately 12 years]
EFS is defined as the time from randomization to disease progression that: precludes surgery, results in a local or distant recurrence, results in a second primary malignancy, or death due to any cause whichever occurs first. The EFS following administration of pembrolizumab and placebo, both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies, as determined by the investigator will be presented.
Secondary Outcome Measures
- Overall Survival (OS) [Up to approximately 12 years]
OS is defined as the time from date of randomization to date of death due to any cause. The OS following administration of pembrolizumab and placebo, both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies will be presented.
- pCR Rate Using the Definition of ypT0ypN0 [Up to approximately 7 months (Time of surgery)]
pCR rate (ypT0ypN0) is defined as the percentage of participants without residual invasive or in situ cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes after completion of neoadjuvant systemic therapy by AJCC staging criteria (8th edition) assessed by the local pathologist at the time of surgery. The percentage of participants with a pCR using the definition of (ypT0ypN0) will be presented for pembrolizumab versus placebo, both in combination with the protocol-specified neoadjuvant anticancer therapies.
- pCR Rate Using the Definition of ypT0/Tis [Up to approximately 7 months (Time of surgery)]
pCR rate (ypT0/Tis) is defined as the percentage of participants without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen (independent of lymph node involvement) after completion of neoadjuvant systemic therapy by AJCC staging criteria (8th edition) assessed by the local pathologist at the time of surgery. The percentage of participants with a pCR using the definition of ypT0/Tis will be presented for pembrolizumab versus placebo, both in combination with the protocol-specified neoadjuvant anticancer therapies.
- pCR Rate Using the Definitions of ypT0/Tis ypN0, ypT0/Tis, and ypT0 ypN0 in Participants With a Combined Positive Score [CPS] ≥1 [Up to approximately 7 months (Time of surgery)]
pCR rates were calculated using the definitions of ypT0/Tis ypN0, ypT0/Tis, and ypT0 ypN0 after completion of neoadjuvant systemic therapy by AJCC staging criteria (8th edition) assessed by the local pathologist at the time of surgery. The percentage of participants with a pCR using the three definitions of ypT0/Tis ypN0, ypT0/Tis, and ypT0 ypN0 in participants with a CPS ≥1 (with a positive Programmed Cell Death-Ligand 1 [PD-L1] tumor status) will be presented for pembrolizumab versus placebo, both in combination with the protocol-specified neoadjuvant anticancer therapies.
- EFS in Participants With a CPS ≥1 [Up to approximately 12 years]
EFS is defined as the time from randomization to disease progression that: precludes surgery, results in a local or distant recurrence, results in a second primary malignancy, or death due to any cause whichever occurs first. The EFS following administration of pembrolizumab and placebo, both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies, as determined by the investigator for participants with a CPS ≥1 will be presented.
- OS in Participants With a CPS ≥1 [Up to approximately 12 years]
OS is defined as the time from date of randomization to date of death due to any cause. The OS following administration of pembrolizumab and placebo, both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies for participants with a CPS ≥1 will be presented.
- Number of Participants Experiencing an Adverse Event (AE) [Up to approximately 15 months]
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE while receiving pembrolizumab or placebo (including 1 month of safety follow up) will be presented.
- Number of Participants Experiencing a Serious Adverse Event (SAE) [Up to approximately 17 months]
An SAE is defined as any untoward medical occurrence that, at any dose: Results in death, Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity or Is a congenital anomaly/birth defect. The number of participants who experience an SAE while receiving pembrolizumab or placebo (including 3 months of safety follow up) will be presented.
- Number of Participants Experiencing an Immune-related AE (irAE) [Up to approximately 15 months]
Some AEs that may occur in this study that are known to be related to pembrolizumab immunotherapy treatment and may include: pneumonitis, diarrhea/colitis, aspartate aminotransferase/alanine aminotransferase (AST/ALT) elevation or increased bilirubin, Type 1 diabetes mellitus or hyperglycemia, hypophysitis, hyperthyroidism, hypothyroidism, nephritis and renal dysfunction, and myocarditis. The number of participants who experience an irAE while receiving pembrolizumab or placebo (including 1 month of safety follow up) will be presented.
- Number of Study Treatment Discontinuations Due to AEs [Up to approximately 14 months]
The number of participants who discontinue study treatment (pembrolizumab or placebo) due to an AE will be presented.
- Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire Core 30 (QLQ-C30) Score [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.]
The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Individual responses for each of 28 items are given on a 4-point scale (1=Not at All to 4=Very Much), with a lower score indicating a better outcome, and responses for each of 2 items (overall health and overall quality of life) are given on a 7-point scale (1=Very poor to 7=Excellent), with a higher score indicating a better outcome. The change from Baseline to end of treatment (up to Cycle 4 Day 1) in EORTC-QLQ-C30 scores for participants will be presented.
- Change from Baseline in EORTC Breast Cancer-Specific QoL Questionnaire (QLQ-BR23) Score [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.]
The EORTC QLQ-BR23 is a 23-item questionnaire developed to assess the quality of life in women with breast cancer. Responses for each item are given on a 4-point scale (1=Not at All to 4=Very Much), with a lower score indicating a better outcome. The change from Baseline to end of treatment (up to Cycle 4 Day 1) in EORTC QLQ-BR23 score for participants will be presented.
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Southern Cancer Center, PC ( Site 8003) | Daphne | Alabama | United States | 36526 |
| 2 | Cancer Treatment Centers of America at Western Regional Medical Center ( Site 0001) | Goodyear | Arizona | United States | 85338 |
| 3 | Arizona Oncology Associates PC- HOPE ( Site 8008) | Tucson | Arizona | United States | 85704 |
| 4 | Cedars Sinai Medical Center Samuel Oschin Comp. Cancer Institute ( Site 0079) | Los Angeles | California | United States | 90048 |
| 5 | El Camino Hospital Cancer Center ( Site 0004) | Mountain View | California | United States | 94040 |
| 6 | Stanford Cancer Center ( Site 0072) | Palo Alto | California | United States | 94304 |
| 7 | UC Davis Comprehensive Cancer Center ( Site 0073) | Sacramento | California | United States | 95817 |
| 8 | University of Colorado Cancer Center ( Site 0008) | Aurora | Colorado | United States | 80045 |
| 9 | Baptist MD Anderson Cancer Center ( Site 0014) | Jacksonville | Florida | United States | 32207 |
| 10 | Southeastern Regional Medical Center, Inc. ( Site 0075) | Newnan | Georgia | United States | 30265 |
| 11 | The University of Chicago Medical Center ( Site 0080) | Chicago | Illinois | United States | 60637 |
| 12 | Orchard Healthcare Research Inc. ( Site 0020) | Skokie | Illinois | United States | 60077 |
| 13 | Midwestern Regional Medical Center, Inc. ( Site 0077) | Zion | Illinois | United States | 60099 |
| 14 | Goshen Center for Cancer Care ( Site 0021) | Goshen | Indiana | United States | 46526 |
| 15 | MercyOne Waterloo Cancer Center ( Site 0016) | Waterloo | Iowa | United States | 50702 |
| 16 | James Graham Brown Cancer Center ( Site 0022) | Louisville | Kentucky | United States | 40202 |
| 17 | Maryland Oncology Hematology, P.A. ( Site 8007) | Bethesda | Maryland | United States | 20817 |
| 18 | Massachusetts General Hospital ( Site 0024) | Boston | Massachusetts | United States | 02114 |
| 19 | MGH - North Shore Cancer Center ( Site 0081) | Danvers | Massachusetts | United States | 01923 |
| 20 | MGH Newton-Wellesley Hospital's Vernon Cancer Center ( Site 0082) | Newton | Massachusetts | United States | 02462 |
| 21 | Henry Ford Health System ( Site 0028) | Detroit | Michigan | United States | 48202 |
| 22 | Mayo Clinic and Medical School (Rochester) ( Site 0029) | Rochester | Minnesota | United States | 55905 |
| 23 | St. Vincent Frontier Cancer Center ( Site 0033) | Billings | Montana | United States | 59102 |
| 24 | Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0039) | Omaha | Nebraska | United States | 68130 |
| 25 | Holy Name Medical Center ( Site 0041) | Teaneck | New Jersey | United States | 07666 |
| 26 | Weill Cornell Medical College ( Site 0043) | New York | New York | United States | 10065 |
| 27 | CTCA Southwestern ( Site 0074) | Tulsa | Oklahoma | United States | 74133 |
| 28 | OHSU Knight Cancer Institute ( Site 0051) | Portland | Oregon | United States | 97239 |
| 29 | Northwest Cancer Specialists, P.C. ( Site 8000) | Tigard | Oregon | United States | 97223 |
| 30 | Geisinger Medical Center ( Site 0052) | Danville | Pennsylvania | United States | 17822 |
| 31 | Fox Chase Cancer Center ( Site 0078) | Philadelphia | Pennsylvania | United States | 19111 |
| 32 | Cancer Treatment Centers of America-Eastern Regional Medical Center ( Site 0076) | Philadelphia | Pennsylvania | United States | 19124 |
| 33 | Medical University of South Carolina ( Site 0053) | Charleston | South Carolina | United States | 29425 |
| 34 | Tennessee Oncology, PLLC/The Sarah Cannon Research Institute ( Site 7000) | Nashville | Tennessee | United States | 37203 |
| 35 | Texas Oncology-Austin Central ( Site 8004) | Austin | Texas | United States | 78731 |
| 36 | Texas Oncology-Dallas Presbyterian Hospital ( Site 8002) | Dallas | Texas | United States | 75231 |
| 37 | Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 8009) | Dallas | Texas | United States | 75246 |
| 38 | Texas Oncology-Memorial City ( Site 8012) | Houston | Texas | United States | 77024 |
| 39 | University of Texas-MD Anderson Cancer Center ( Site 0083) | Houston | Texas | United States | 77030-4009 |
| 40 | Texas Oncology- Plano East ( Site 8010) | Plano | Texas | United States | 75075 |
| 41 | Texas Oncology-Tyler ( Site 8006) | Tyler | Texas | United States | 75702 |
| 42 | Bon Secours St. Francis Medical Center Oncology Research ( Site 0064) | Midlothian | Virginia | United States | 23114 |
| 43 | Virginia Oncology Associates ( Site 8001) | Norfolk | Virginia | United States | 23502 |
| 44 | Kadlec Clinic Hematology and Oncology ( Site 0070) | Kennewick | Washington | United States | 99336 |
| 45 | Medical Oncology Associates (Summit Cancer Centers) ( Site 0066) | Spokane | Washington | United States | 99208 |
| 46 | Chris OBrien Lifehouse ( Site 2107) | Camperdown | New South Wales | Australia | 2050 |
| 47 | Royal North Shore Hospital ( Site 2100) | Sydney | New South Wales | Australia | 2065 |
| 48 | Westmead Hospital ( Site 2101) | Sydney | New South Wales | Australia | 2145 |
| 49 | Mater Misericordiae Ltd ( Site 2106) | South Brisbane | Queensland | Australia | 4101 |
| 50 | Frankston Hospital ( Site 2103) | Frankston | Victoria | Australia | 3199 |
| 51 | Peter MacCallum Cancer Centre ( Site 2102) | Melbourne | Victoria | Australia | 3000 |
| 52 | Imelda Ziekenhuis Bonheiden ( Site 0703) | Bonheiden | Antwerpen | Belgium | 2820 |
| 53 | UZ Antwerpen - Medical Oncology ( Site 0709) | Edegem | Antwerpen | Belgium | 2650 |
| 54 | Institut Jules Bordet ( Site 0710) | Anderlecht | Bruxelles-Capitale, Region De | Belgium | 1070 |
| 55 | Cliniques Universitaires Saint-Luc ( Site 0701) | Brussels | Bruxelles-Capitale, Region De | Belgium | 1200 |
| 56 | CHC MontLegia ( Site 0707) | Liège | Liege | Belgium | 4000 |
| 57 | Jessa Ziekenhuis Campus Virga Jesse ( Site 0704) | Hasselt | Limburg | Belgium | 3500 |
| 58 | CHU UCL Namur Site de Godinne ( Site 0706) | Yvoir | Namur | Belgium | 5530 |
| 59 | AZ Maria Middelares Gent ( Site 0700) | Gent | Oost-Vlaanderen | Belgium | 9000 |
| 60 | UZ Leuven ( Site 0702) | Leuven | Vlaams-Brabant | Belgium | 3000 |
| 61 | AZ Groeninge ( Site 0705) | Kortrijk | West-Vlaanderen | Belgium | 8500 |
| 62 | Hospital Araujo Jorge Associacao de Combate ao Cancer de Goias ( Site 0205) | Goiania | Goias | Brazil | 74605-070 |
| 63 | ONCOSITE - Centro de Pesquisa Clinica em Oncologia ( Site 0206) | Ijui | Rio Grande Do Sul | Brazil | 98700-000 |
| 64 | Associacao Hospitalar Moinhos de Vento ( Site 0201) | Porto Alegre | Rio Grande Do Sul | Brazil | 90035-001 |
| 65 | Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0202) | Porto Alegre | Rio Grande Do Sul | Brazil | 90610-000 |
| 66 | CEPON - Centro de Pesquisas Oncologicas ( Site 0208) | Florianopolis | Santa Catarina | Brazil | 88034-000 |
| 67 | Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral ( Site 0207) | Itajai | Santa Catarina | Brazil | 88301-220 |
| 68 | Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 0210) | São Paulo | Sao Paulo | Brazil | 04014-002 |
| 69 | Instituto Nacional de Cancer - INCA HC III ( Site 0200) | Rio de Janeiro | Brazil | 20560-120 | |
| 70 | Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0209) | Sao Paulo | Brazil | 01246-000 | |
| 71 | Clinica de Pesquisas e Ctro de Estudos Onc. Ginecol. e Mamaria Ltda ( Site 0204) | Sao Paulo | Brazil | 01317-001 | |
| 72 | Cross Cancer Institute ( Site 0115) | Edmonton | Alberta | Canada | T6G 1Z2 |
| 73 | BC Cancer-Vancouver Center ( Site 0116) | Vancouver | British Columbia | Canada | V5Z 4E6 |
| 74 | Princess Margaret Cancer Centre ( Site 0112) | Toronto | Ontario | Canada | M5G 2M9 |
| 75 | CISSS de la Monteregie-Centre ( Site 0108) | Greenfield Park | Quebec | Canada | J4V 2H1 |
| 76 | Hopital Maisonneuve-Rosemont CIUSSS de l Est de L Ile de Montreal ( Site 0111) | Montreal | Quebec | Canada | H1T 2M4 |
| 77 | Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0114) | Montreal | Quebec | Canada | H2X 3E4 |
| 78 | Jewish General Hospital ( Site 0103) | Montreal | Quebec | Canada | H3T 1E2 |
| 79 | Centre Hospitalier Regional de Trois-Rivieres ( Site 0106) | Trois-Rivières | Quebec | Canada | G8Z 3R9 |
| 80 | CHU de Quebec Universite Laval - Hopital du Saint-Sacrement ( Site 0101) | Quebec | Canada | G1S 4L8 | |
| 81 | Anhui Provincial Hospital ( Site 3224) | Heifei | Anhui | China | 230001 |
| 82 | Ruijin Hosp,Shanghai Jiao Tong University School of Medicine ( Site 3215) | Shanghai | Anhui | China | 200025 |
| 83 | Cancer Hospital Chinese Academy of Medical Sciences ( Site 3208) | Beijing | Beijing | China | 100021 |
| 84 | Fujian Medical University Union Hospital-1 Bingfanglou-Oncology ( Site 3207) | Fuzhou Fujian | Fujian | China | 350001 |
| 85 | Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University ( Site 3213) | Guangzhou | Guangdong | China | 510289 |
| 86 | Fourth Hospital Of Hebei Medical University ( Site 3216) | Shijia Zhuang | Hebei | China | 050019 |
| 87 | Harbin Medical University Cancer Hospital ( Site 3200) | Harbin | Heilongjiang | China | 150081 |
| 88 | Henan Cancer Hospital ( Site 3212) | Zhengzhou | Henan | China | 450008 |
| 89 | Hubei Cancer Hospital ( Site 3211) | Wuhan | Hubei | China | 430079 |
| 90 | Hunan Cancer Hospital ( Site 3214) | Changsha | Hunan | China | 410006 |
| 91 | The First Affiliated Hospital of Zhejiang University ( Site 3203) | Hangzhou | Jiangsu | China | 310003 |
| 92 | The First Hospital of Jilin University ( Site 3201) | Changchun | Jilin | China | 130021 |
| 93 | Fudan University Shanghai Cancer Center ( Site 3205) | Shanghai | Shanghai | China | 200032 |
| 94 | The First Affiliated Hospital of Xi an Jiaotong University ( Site 3220) | XI An | Shanxi | China | 710061 |
| 95 | Tianjin Medical University Cancer Institute & Hospital ( Site 3209) | Tianjin | Tianjin | China | 300060 |
| 96 | Cancer Hospital Affiliated to Xinjiang Medical University ( Site 3219) | Urumqi | Xinjiang | China | 830000 |
| 97 | Zhejiang Provincial People's Hospital ( Site 3225) | Hangzhou | Zhejiang | China | 310014 |
| 98 | Zhejiang Cancer Hospital.... ( Site 3210) | Hangzhou | Zhejiang | China | 310022 |
| 99 | Clínica Vida Fundación - Sede Poblado ( Site 0405) | Medellin | Antioquia | Colombia | 050030 |
| 100 | Rodrigo Botero SAS ( Site 0407) | Medellin | Antioquia | Colombia | 050030 |
| 101 | Clinica de la Costa Ltda. ( Site 0400) | Barranquilla | Atlantico | Colombia | 080020 |
| 102 | Oncomedica S.A. ( Site 0401) | Monteria | Cordoba | Colombia | 230001 |
| 103 | Centro de Investigacion Clinica del Country ( Site 0402) | Bogota | Distrito Capital De Bogota | Colombia | 110221 |
| 104 | Fundacion Universitaria Sanitas ( Site 0403) | Bogota | Distrito Capital De Bogota | Colombia | 111221 |
| 105 | Centro Medico Imbanaco de Cali S.A ( Site 0406) | Cali | Valle Del Cauca | Colombia | 760042 |
| 106 | Hospital Metropolitano - Sede Lindora ( Site 4203) | Santa Ana | San Jose | Costa Rica | 10903 |
| 107 | Centre Francois Baclesse ( Site 0927) | Caen | Calvados | France | 14000 |
| 108 | Centre Georges Francois Leclerc ( Site 0920) | Dijon | Cote-d Or | France | 21079 |
| 109 | Institut Claudius Regaud IUCT Oncopole ( Site 0903) | Toulouse | Haute-Garonne | France | 31059 |
| 110 | Institut Curie - Centre Rene Huguenin ( Site 0917) | Saint-Cloud | Hauts-de-Seine | France | 92210 |
| 111 | Centre de Cancerologie du Grand Montpellier ( Site 0925) | Montpellier | Herault | France | 34070 |
| 112 | CHR-METZ-THIONVILLE - Hopital de Mercy ( Site 0919) | Metz | Moselle | France | 57085 |
| 113 | Centre Oscar Lambret ( Site 0911) | Lille | Nord-Pas-de-Calais | France | 59000 |
| 114 | Institut Sainte Catherine ( Site 0916) | Avignon | Provence-Alpes-Cote-d Azur | France | 84918 |
| 115 | Centre Jean Perrin ( Site 0909) | Clermont Ferrand Cedex | Puy-de-Dome | France | 63011 |
| 116 | Clinique Victor Hugo ( Site 0906) | Le Mans | Sarthe | France | 72000 |
| 117 | Institut Gustave Roussy ( Site 0926) | Villejuif | Val-de-Marne | France | 94805 |
| 118 | Institut Curie ( Site 0900) | Paris | France | 75005 | |
| 119 | Hopital Saint-Louis ( Site 0908) | Paris | France | 75010 | |
| 120 | Hopital Tenon ( Site 0914) | Paris | France | 75020 | |
| 121 | Medizinische Management GmbH ( Site 1012) | Friedrichshafen | Baden-Wurttemberg | Germany | 88045 |
| 122 | Universitaetsklinikum Erlangen ( Site 1001) | Erlangen | Bayern | Germany | 91054 |
| 123 | Klinikum der Universitaet Muenchen - Grosshadern ( Site 1000) | Muenchen | Bayern | Germany | 80337 |
| 124 | Sana Klinikum Offenbach GmbH ( Site 1002) | Offenbach | Hessen | Germany | 63069 |
| 125 | HELIOS Dr. Horst Schmidt Kliniken Wiesbaden ( Site 1004) | Wiesbaden | Hessen | Germany | 65199 |
| 126 | Gynaekologisch-onkologische Praxis Hannover ( Site 1013) | Hannover | Niedersachsen | Germany | 30177 |
| 127 | Gynaekologisches Zentrum ( Site 1003) | Bonn | Nordrhein-Westfalen | Germany | 53111 |
| 128 | Kliniken Essen Mitte Gmbh Evang. Huyssens Stiftung ( Site 1006) | Essen | Nordrhein-Westfalen | Germany | 45136 |
| 129 | Frauenklinik St. Louise ( Site 1014) | Paderborn | Nordrhein-Westfalen | Germany | 60314 |
| 130 | Caritas Klinikum Saarbruecken St. Theresia ( Site 1009) | Saarbruecken | Saarland | Germany | 66113 |
| 131 | Universitaetsklinikum Carl Gustav Carus ( Site 1008) | Dresden | Sachsen | Germany | 01307 |
| 132 | MVZ Nordhausen gGmbH - Praxis Dr. Grafe ( Site 1005) | Nordhausen | Thuringen | Germany | 99734 |
| 133 | Bacs-Kiskun Megyei Korhaz ( Site 2913) | Kecskemet | Bacs-Kiskun | Hungary | 6000 |
| 134 | Pecsi Tudomanyegyetem Klinikai Kozpont ( Site 2905) | Pecs | Baranya | Hungary | 7621 |
| 135 | Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi OktatoKorhaz ( Site 2904) | Miskolc | Borsod-Abauj-Zemplen | Hungary | 3526 |
| 136 | Szent Margit Korhaz ( Site 2901) | Budapest | Hungary | 1032 | |
| 137 | Orszagos Onkologiai Intezet ( Site 2908) | Budapest | Hungary | 1122 | |
| 138 | Uzsoki Utcai Korhaz ( Site 2902) | Budapest | Hungary | 1145 | |
| 139 | Debreceni Egyetem Klinikai Kozpont ( Site 2907) | Debrecen | Hungary | 4032 | |
| 140 | Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 2915) | Kaposvar | Hungary | 7400 | |
| 141 | Bon Secours Hospital ( Site 1554) | Cork | Ireland | T12 DV56 | |
| 142 | St. James s Hospital ( Site 1553) | Dublin | Ireland | 8 | |
| 143 | HaEmek Medical Center ( Site 1712) | Afula | Israel | 1834111 | |
| 144 | Assuta Ashdod Public ( Site 1704) | Ashdod | Israel | 7747629 | |
| 145 | Soroka Medical Center ( Site 1701) | Beer Sheva | Israel | 8410101 | |
| 146 | Rambam Health Care Campus-Oncology Division ( Site 1705) | Haifa | Israel | 3109601 | |
| 147 | Shaare Zedek Medical Center ( Site 1708) | Jerusalem | Israel | 9103102 | |
| 148 | Hadassah Ein Karem - Sharett Institute of Oncology ( Site 1700) | Jerusalem | Israel | 9112001 | |
| 149 | Meir Medical Center ( Site 1710) | Kfar-Saba | Israel | 4428164 | |
| 150 | Holy Family Hospital ( Site 1711) | Nazareth | Israel | 1641101 | |
| 151 | Rabin Medical Center ( Site 1702) | Petah Tikva | Israel | 4941492 | |
| 152 | Chaim Sheba Medical Center. ( Site 1707) | Ramat Gan | Israel | 5262000 | |
| 153 | Kaplan Medical Center ( Site 1703) | Rehovot | Israel | 7661041 | |
| 154 | Sourasky Medical Center ( Site 1706) | Tel Aviv | Israel | 6423906 | |
| 155 | Assuta Medical Center ( Site 1709) | Tel Aviv | Israel | 6789140 | |
| 156 | Aichi Cancer Center Hospital ( Site 2601) | Nagoya | Aichi | Japan | 464-8681 |
| 157 | National Cancer Center Hospital East ( Site 2613) | Kashiwa | Chiba | Japan | 2778577 |
| 158 | National Hospital Organization Hokkaido Cancer Center ( Site 2607) | Sapporo | Hokkaido | Japan | 003-0804 |
| 159 | Hyogo College of Medicine Hospital ( Site 2600) | Nishinomiya | Hyogo | Japan | 663-8501 |
| 160 | Kitasato University Hospital ( Site 2616) | Sagamihara | Kanagawa | Japan | 252-0375 |
| 161 | Saitama Medical University International Medical Center ( Site 2606) | Hidaka | Saitama | Japan | 350-1298 |
| 162 | Saitama Cancer Center ( Site 2612) | Kitaadachi-gun | Saitama | Japan | 362-0806 |
| 163 | Shizuoka Cancer Center Hospital and Research Institute ( Site 2611) | Sunto-gun | Shizuoka | Japan | 411-8777 |
| 164 | Chiba Cancer Center ( Site 2605) | Chiba | Japan | 260-8717 | |
| 165 | Fukushima Medical University Hospital ( Site 2610) | Fukushima | Japan | 960-1295 | |
| 166 | Hiroshima City Hiroshima Citizens Hospital ( Site 2603) | Hiroshima | Japan | 730-8518 | |
| 167 | Kumamoto University Hospital ( Site 2602) | Kumamoto | Japan | 860-8556 | |
| 168 | National Hospital Organization - Osaka National Hospital - Institute For Clinical Research ( Site 26 | Osaka | Japan | 540-0006 | |
| 169 | Toranomon Hospital ( Site 2608) | Tokyo | Japan | 105-8470 | |
| 170 | The Cancer Institute Hospital of JFCR ( Site 2604) | Tokyo | Japan | 135-8550 | |
| 171 | Showa University Hospital ( Site 2615) | Tokyo | Japan | 142-8666 | |
| 172 | National Cancer Center ( Site 2204) | Goyang-si | Kyonggi-do | Korea, Republic of | 10408 |
| 173 | Asan Medical Center ( Site 2202) | Songpagu | Seoul | Korea, Republic of | 05505 |
| 174 | Seoul National University Hospital ( Site 2200) | Seoul | Korea, Republic of | 03080 | |
| 175 | Severance Hospital Yonsei University Health System ( Site 2201) | Seoul | Korea, Republic of | 03722 | |
| 176 | Samsung Medical Center ( Site 2203) | Seoul | Korea, Republic of | 06351 | |
| 177 | Tauranga Hospital ( Site 2302) | Tauranga | Bay Of Plenty | New Zealand | 3112 |
| 178 | Canterbury Regional Cancer & Blood Services ( Site 2303) | Christchurch | Canterbury | New Zealand | 8011 |
| 179 | Capital & Coast District Health Board - Wellington Hospital ( Site 2301) | Wellington | New Zealand | 6021 | |
| 180 | Dolnoslaskie Centrum Onkologii. ( Site 1820) | Wrocław | Dolnoslaskie | Poland | 53-413 |
| 181 | Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1800) | Bydgoszcz | Kujawsko-pomorskie | Poland | 85-796 |
| 182 | Instytut Centrum Zdrowia Matki Polki ( Site 1821) | Lodz | Lodzkie | Poland | 93-338 |
| 183 | Mazowiecki Szpital Specjalistyczny im. dr Jozefa Psarskiego ( Site 1814) | Ostroleka | Mazowieckie | Poland | 07-410 |
| 184 | Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie ( | Warszawa | Mazowieckie | Poland | 02-781 |
| 185 | Mazowiecki Szpital Onkologiczny ( Site 1803) | Wieliszew | Mazowieckie | Poland | 05-135 |
| 186 | Bialostockie Centrum Onkologii ( Site 1819) | Bialystok | Podlaskie | Poland | 15-027 |
| 187 | Wojewodzkie Centrum Onkologii Copernicus ( Site 1817) | Gdansk | Pomorskie | Poland | 80-219 |
| 188 | Szpitale Pomorskie Sp. z o.o. ( Site 1818) | Gdynia | Pomorskie | Poland | 81-519 |
| 189 | Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 1810) | Bielsko-Biala | Slaskie | Poland | 43-300 |
| 190 | Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu ( Site 1807) | Bytom | Slaskie | Poland | 41-900 |
| 191 | Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 1801) | Gliwice | Slaskie | Poland | 44-101 |
| 192 | Fundacao Champalimaud ( Site 2500) | Lisboa | Aveiro | Portugal | 1649-035 |
| 193 | CHLN Hospital Santa Maria ( Site 2501) | Lisboa | Portugal | 1649-035 | |
| 194 | Hospital Geral de Santo Antonio ( Site 2503) | Porto | Portugal | 4099-001 | |
| 195 | Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 2502) | Porto | Portugal | 4200-072 | |
| 196 | UPR Comprehensive Cancer Center ( Site 6200) | San Juan | Puerto Rico | 00935 | |
| 197 | Arkhangelsk Clinical Oncological Dispensary ( Site 1901) | Arkhangelsk | Arkhangel Skaya Oblast | Russian Federation | 163045 |
| 198 | Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1909) | Ufa | Baskortostan, Respublika | Russian Federation | 450054 |
| 199 | N.N. Blokhin NMRCO ( Site 1908) | Moscow | Moskva | Russian Federation | 115478 |
| 200 | Central Clinical Hospital with outpatient Clinic ( Site 1907) | Moscow | Moskva | Russian Federation | 121359 |
| 201 | Medical Rehabilitation Center ( Site 1912) | Moscow | Moskva | Russian Federation | 125367 |
| 202 | Ryazan Regional Clinical Oncology Dispensary ( Site 1910) | Ryazan | Ryazanskaya Oblast | Russian Federation | 390013 |
| 203 | Railway Hospital of OJSC ( Site 1913) | Saint Petersburg | Sankt-Peterburg | Russian Federation | 195271 |
| 204 | Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1900) | Saint Petersburg | Sankt-Peterburg | Russian Federation | 197758 |
| 205 | Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1903) | Kazan | Tatarstan, Respublika | Russian Federation | 420029 |
| 206 | Tomsk Scientific Research Institute of Oncology ( Site 1905) | Tomsk | Tomskaya Oblast | Russian Federation | 634028 |
| 207 | Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 1363) | Hospitalet de Llobregat | Barcelona | Spain | 08908 |
| 208 | Hospital Teresa Herrera - Chuac ( Site 1358) | A Coruna | La Coruna | Spain | 15006 |
| 209 | Hospital General Universitario Gregorio Maranon ( Site 1367) | Madrid | Madrid, Comunidad De | Spain | 28007 |
| 210 | Hospital Quiron de Madrid ( Site 1351) | Pozuelo de Alarcon | Madrid | Spain | 28223 |
| 211 | Hospital Clinico Universitario de Valencia ( Site 1355) | Valencia | Valenciana, Comunitat | Spain | 46011 |
| 212 | Instituto Oncologico Baselga.Hospital Quiron. ( Site 1352) | Barcelona | Spain | 08023 | |
| 213 | Hospital Vall D Hebron ( Site 1357) | Barcelona | Spain | 08035 | |
| 214 | Hospital Clinic I Provincial de Barcelona ( Site 1353) | Barcelona | Spain | 08036 | |
| 215 | Complejo Hospitalario de Jaen ( Site 1364) | Jaen | Spain | 23007 | |
| 216 | Hospital Ruber Internacional ( Site 1370) | Madrid | Spain | 28034 | |
| 217 | Hospital Clinico San Carlos ( Site 1354) | Madrid | Spain | 28040 | |
| 218 | Hospital Universitario 12 de Octubre ( Site 1356) | Madrid | Spain | 28041 | |
| 219 | Hospital Universitario Virgen del Rocio ( Site 1360) | Sevilla | Spain | 41013 | |
| 220 | Hospital General Arnau de Vilanova de Valencia ( Site 1369) | Valencia | Spain | 46015 | |
| 221 | China Medical University Hospital ( Site 2401) | Taichung | Taiwan | 40447 | |
| 222 | National Cheng Kung University Hospital ( Site 2400) | Tainan | Taiwan | 704 | |
| 223 | National Taiwan University Hospital ( Site 2404) | Taipei | Taiwan | 10048 | |
| 224 | Koo Foundation Sun Yat-Sen Cancer Center ( Site 2403) | Taipei | Taiwan | 11259 | |
| 225 | Linkou Chang Gung Memorial Hospital ( Site 2402) | Taoyuan | Taiwan | 333 | |
| 226 | Dnipropetrovsk City Multidiscipline Clinical Hosp. 4 of DRC ( Site 2702) | Dnipro | Dnipropetrovska Oblast | Ukraine | 49102 |
| 227 | MI Kryviy Rih Center of Dnipropetrovsk Regional Council ( Site 2700) | Kryviy Rih | Dnipropetrovska Oblast | Ukraine | 50048 |
| 228 | MI Precarpathian Clinical Oncology Center ( Site 2707) | Ivano-Frankivsk | Ivano-Frankivska Oblast | Ukraine | 76018 |
| 229 | Communal non profit enterprise Regional Clinical Oncology Center ( Site 2721) | Kharkiv | Kharkivska Oblast | Ukraine | 61070 |
| 230 | Communal nonprofit enterprise "Kherson Regional Oncology Dispensary" of Kherson Regional Council ( | Antonivka Village | Khersonska Oblast | Ukraine | 73000 |
| 231 | Khmelnitskiy Regional Onkology Dispensary ( Site 2704) | Khmelnitskiy | Khmelnytska Oblast | Ukraine | 29000 |
| 232 | National Cancer Institute of the MoH of Ukraine ( Site 2719) | Kyiv | Kyivska Oblast | Ukraine | 03022 |
| 233 | MI Odesa Regional Clinical Hospital ( Site 2701) | Odesa | Odeska Oblast | Ukraine | 65025 |
| 234 | MI Odessa Regional Oncological Centre ( Site 2714) | Odesa | Odeska Oblast | Ukraine | 65055 |
| 235 | Medical center of the Limited Liability Company Yulis ( Site 2720) | Zaporizhzhia | Zaporizka Oblast | Ukraine | 69035 |
| 236 | Kyiv City Clinical Oncology Centre ( Site 2716) | Kyiv | Ukraine | 03115 | |
| 237 | University Hospitals Bristol NHS Foundation Trust ( Site 1503) | Bristol | Bristol, City Of | United Kingdom | BS2 8ED |
| 238 | Nottingham University Hospitals NHS Trust ( Site 1504) | Nottingham | England | United Kingdom | ng5 1pb |
| 239 | Colchester General Hospital ( Site 1508) | Colchester | Essex | United Kingdom | CO4 5JL |
| 240 | Barts Health NHS Trust ( Site 1500) | London | London, City Of | United Kingdom | EC1A 7BE |
| 241 | Guy's Hospital ( Site 1501) | London | London, City Of | United Kingdom | SE1 9RY |
| 242 | St. Georges University Hospital NHS Foundation Trust ( Site 1505) | London | London, City Of | United Kingdom | SW17 0QT |
| 243 | Birmingham & Solihull Heartlands Hospital NHS ( Site 1506) | Solihull | United Kingdom | B91 2JL | |
| 244 | Royal Cornwall Hospital ( Site 1502) | Truro | United Kingdom | TR1 3LJ |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 3475-756
- MK-3475-756
- 194604
- KEYNOTE-756
- 2017-004869-27