Study of Pembrolizumab (MK-3475) in Combination With Adjuvant Chemotherapy With or Without Radiotherapy in Participants With Newly Diagnosed Endometrial Cancer After Surgery With Curative Intent (MK-3475-B21 / KEYNOTE-B21 / ENGOT-en11 / GOG-3053)

Sponsor

Merck Sharp & Dohme LLC (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04634877

Collaborator

European Network for Gynaecological Oncological Trial Groups (Other), Gynecologic Oncology Group (Other)

990

Enrollment

230

Locations

Arms

53.2

Anticipated Duration (Months)

4.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to compare pembrolizumab + adjuvant chemotherapy with placebo + adjuvant chemotherapy, with or without radiotherapy, with respect to disease-free survival (DFS) as assessed radiographically by the investigator or by histopathologic confirmation of suspected disease recurrence, and with respect to overall survival (OS). The primary hypotheses are that pembrolizumab + adjuvant chemotherapy is superior to placebo + adjuvant chemotherapy, with or without radiotherapy, with respect to DFS as assessed radiographically by the investigator or by histopathologic confirmation of suspected disease recurrence, and with respect to OS.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Neoplasms	Biological: Pembrolizumab Drug: Carboplatin Drug: Paclitaxel Drug: Placebo for pembrolizumab Drug: Docetaxel Drug: Cisplatin Radiation: External Beam Radiotherapy (EBRT) Drug: Cisplatin (as radiosensitizer) Radiation: Brachytherapy	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

990 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 3, Randomized, Double-Blind Study of Pembrolizumab Versus Placebo in Combination With Adjuvant Chemotherapy With or Without Radiotherapy for the Treatment of Newly Diagnosed High-Risk Endometrial Cancer After Surgery With Curative Intent (KEYNOTE-B21 / ENGOT-en11 / GOG-3053)

Actual Study Start Date :

Jan 10, 2021

Anticipated Primary Completion Date :

Jun 18, 2025

Anticipated Study Completion Date :

Jun 18, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pembrolizumab + Chemotherapy Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for 6 cycles followed by pembrolizumab 400 mg IV on Day 1 of each 6-week cycle (Q6W) for an additional 6 cycles. During the Q3W dosing period of pembrolizumab, participants receive concurrent standard of care (SoC) chemotherapy for 4 or 6 cycles. Participants optionally receive radiotherapy starting within 6 weeks of completion of SoC chemotherapy. The SoC chemotherapy regimen includes carboplatin AUC 5 or 6 IV Q3W plus paclitaxel 175 mg/m^2 IV Q3W. In the event of severe hypersensitivity to, or an AE requiring discontinuation of, carboplatin or paclitaxel, cisplatin or docetaxel may be substituted after investigator consults with sponsor. The SoC radiotherapy regimen may include, at the discretion of the investigator, external beam radiotherapy (EBRT) ≥4500 cGY with variable dose frequency, with or without cisplatin 50 mg/m^2 IV on days 1 and 29 of EBRT, and/or brachytherapy radiation.	Biological: Pembrolizumab IV infusion Other Names: KEYTRUDA® MK-3475 Drug: Carboplatin IV infusion Drug: Paclitaxel IV infusion Drug: Docetaxel IV infusion docetaxel 75 mg/m^2 Q3W or 25 mg/m2 QW may be given in place of paclitaxel following sponsor consultation if a participant experiences severe hypersensitivity to paclitaxel or an adverse event requiring discontinuation of paclitaxel. Drug: Cisplatin Cisplatin 75 mg/m^2 IV infusion Q3W may be given in place of carboplatin following sponsor consultation if a participant experiences severe hypersensitivity to carboplatin or an adverse event requiring discontinuation of carboplatin. Other Names: Platinol® Platinol®-AQ Radiation: External Beam Radiotherapy (EBRT) ≥4500 cGY given according to local practice, at the discretion of the investigator Drug: Cisplatin (as radiosensitizer) If a participant receives external beam radiotherapy (EBRT), then cisplatin 50 mg/m^2 IV infusion may be administered as a radiosensitizer at the discretion of the investigator, on days 1 and 29 Other Names: Platinol® Platinol®-AQ Radiation: Brachytherapy Given according to local practice, at the discretion of the investigator Other Names: Internal radiation therapy
Placebo Comparator: Placebo + Chemotherapy Participants receive placebo to pembrolizumab intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for 6 cycles followed by placebo IV on Day 1 of each 6-week cycle (Q6W) for an additional 6 cycles. During the Q3W dosing period of placebo, participants receive concurrent standard of care (SoC) chemotherapy for 4 or 6 cycles. Participants optionally receive radiotherapy starting within 6 weeks of completion of SoC chemotherapy. The SoC chemotherapy regimen includes carboplatin AUC 5 or 6 IV Q3W plus paclitaxel 175 mg/m^2 IV Q3W. In the event of severe hypersensitivity to, or an AE requiring discontinuation of, carboplatin or paclitaxel, cisplatin or docetaxel may be substituted after investigator consults with sponsor. The SoC radiotherapy regimen may include, at the discretion of the investigator, external beam radiotherapy (EBRT) ≥4500 cGY with variable dose frequency, with or without cisplatin 50 mg/m^2 IV on days 1 and 29 of EBRT, and/or brachytherapy radiation.	Drug: Carboplatin IV infusion Drug: Paclitaxel IV infusion Drug: Placebo for pembrolizumab IV infusion Drug: Docetaxel IV infusion docetaxel 75 mg/m^2 Q3W or 25 mg/m2 QW may be given in place of paclitaxel following sponsor consultation if a participant experiences severe hypersensitivity to paclitaxel or an adverse event requiring discontinuation of paclitaxel. Drug: Cisplatin Cisplatin 75 mg/m^2 IV infusion Q3W may be given in place of carboplatin following sponsor consultation if a participant experiences severe hypersensitivity to carboplatin or an adverse event requiring discontinuation of carboplatin. Other Names: Platinol® Platinol®-AQ Radiation: External Beam Radiotherapy (EBRT) ≥4500 cGY given according to local practice, at the discretion of the investigator Drug: Cisplatin (as radiosensitizer) If a participant receives external beam radiotherapy (EBRT), then cisplatin 50 mg/m^2 IV infusion may be administered as a radiosensitizer at the discretion of the investigator, on days 1 and 29 Other Names: Platinol® Platinol®-AQ Radiation: Brachytherapy Given according to local practice, at the discretion of the investigator Other Names: Internal radiation therapy

Arm

Intervention/Treatment

Experimental: Pembrolizumab + Chemotherapy

Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for 6 cycles followed by pembrolizumab 400 mg IV on Day 1 of each 6-week cycle (Q6W) for an additional 6 cycles. During the Q3W dosing period of pembrolizumab, participants receive concurrent standard of care (SoC) chemotherapy for 4 or 6 cycles. Participants optionally receive radiotherapy starting within 6 weeks of completion of SoC chemotherapy. The SoC chemotherapy regimen includes carboplatin AUC 5 or 6 IV Q3W plus paclitaxel 175 mg/m^2 IV Q3W. In the event of severe hypersensitivity to, or an AE requiring discontinuation of, carboplatin or paclitaxel, cisplatin or docetaxel may be substituted after investigator consults with sponsor. The SoC radiotherapy regimen may include, at the discretion of the investigator, external beam radiotherapy (EBRT) ≥4500 cGY with variable dose frequency, with or without cisplatin 50 mg/m^2 IV on days 1 and 29 of EBRT, and/or brachytherapy radiation.

Biological: Pembrolizumab

IV infusion

Other Names:

KEYTRUDA®

MK-3475

Drug: Carboplatin

IV infusion

Drug: Paclitaxel

IV infusion

Drug: Docetaxel

IV infusion docetaxel 75 mg/m^2 Q3W or 25 mg/m2 QW may be given in place of paclitaxel following sponsor consultation if a participant experiences severe hypersensitivity to paclitaxel or an adverse event requiring discontinuation of paclitaxel.

Drug: Cisplatin

Cisplatin 75 mg/m^2 IV infusion Q3W may be given in place of carboplatin following sponsor consultation if a participant experiences severe hypersensitivity to carboplatin or an adverse event requiring discontinuation of carboplatin.

Other Names:

Platinol®

Platinol®-AQ

Radiation: External Beam Radiotherapy (EBRT)

≥4500 cGY given according to local practice, at the discretion of the investigator

Drug: Cisplatin (as radiosensitizer)

If a participant receives external beam radiotherapy (EBRT), then cisplatin 50 mg/m^2 IV infusion may be administered as a radiosensitizer at the discretion of the investigator, on days 1 and 29

Other Names:

Platinol®

Platinol®-AQ

Radiation: Brachytherapy

Given according to local practice, at the discretion of the investigator

Other Names:

Internal radiation therapy

Placebo Comparator: Placebo + Chemotherapy

Participants receive placebo to pembrolizumab intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for 6 cycles followed by placebo IV on Day 1 of each 6-week cycle (Q6W) for an additional 6 cycles. During the Q3W dosing period of placebo, participants receive concurrent standard of care (SoC) chemotherapy for 4 or 6 cycles. Participants optionally receive radiotherapy starting within 6 weeks of completion of SoC chemotherapy. The SoC chemotherapy regimen includes carboplatin AUC 5 or 6 IV Q3W plus paclitaxel 175 mg/m^2 IV Q3W. In the event of severe hypersensitivity to, or an AE requiring discontinuation of, carboplatin or paclitaxel, cisplatin or docetaxel may be substituted after investigator consults with sponsor. The SoC radiotherapy regimen may include, at the discretion of the investigator, external beam radiotherapy (EBRT) ≥4500 cGY with variable dose frequency, with or without cisplatin 50 mg/m^2 IV on days 1 and 29 of EBRT, and/or brachytherapy radiation.

Drug: Carboplatin

IV infusion

Drug: Paclitaxel

IV infusion

Drug: Placebo for pembrolizumab

IV infusion

Drug: Docetaxel

Drug: Cisplatin

Other Names:

Platinol®

Platinol®-AQ

Radiation: External Beam Radiotherapy (EBRT)

≥4500 cGY given according to local practice, at the discretion of the investigator

Drug: Cisplatin (as radiosensitizer)

If a participant receives external beam radiotherapy (EBRT), then cisplatin 50 mg/m^2 IV infusion may be administered as a radiosensitizer at the discretion of the investigator, on days 1 and 29

Other Names:

Platinol®

Platinol®-AQ

Radiation: Brachytherapy

Given according to local practice, at the discretion of the investigator

Other Names:

Internal radiation therapy

Outcome Measures

Primary Outcome Measures

Disease-Free Survival (DFS) as Assessed Radiographically by Investigator or by Histopathologic Confirmation of Suspected Disease Recurrence [Up to approximately 42 months]
DFS is defined as the time from randomization to the first documented local recurrence, distant metastasis, secondary systemic malignancy, or death due to any cause, whichever occurs first. The DFS as assessed radiographically by investigator or by histopathologic confirmation of suspected disease recurrence, will be presented.
Overall Survival (OS) [Up to approximately 54 months]
OS is defined as the time from randomization to death due to any cause.

Secondary Outcome Measures

Disease-Free Survival (DFS) as Assessed Radiographically by Blinded Independent Central Review (BICR) or by Histopathologic Confirmation of Suspected Disease Recurrence [Up to approximately 42 months]
DFS is defined as the time from randomization to the first documented local recurrence, distant metastasis, secondary systemic malignancy, or death due to any cause, whichever occurs first. The DFS as assessed radiographically by BICR or by histopathologic confirmation of suspected disease recurrence, will be presented.
Disease-Free Survival (DFS) as Assessed Radiographically by Investigator or by Histopathologic Confirmation of Suspected Disease Recurrence by Combined Positivity Score (CPS)-Determined Programmed Cell Death 1 Ligand 1 (PD-L1) Status [Up to approximately 42 months]
DFS is defined as the time from randomization to the first documented local recurrence, distant metastasis, secondary systemic malignancy, or death due to any cause, whichever occurs first. The DFS as assessed radiographically by investigator or by histopathologic confirmation of suspected disease recurrence by CPS-determined PD-L1 status will be presented.
Overall Survival (OS) as Assessed Radiographically by Investigator or by Histopathologic Confirmation of Suspected Disease Recurrence by Combined Positivity Score (CPS)-Determined Programmed Cell Death 1 Ligand 1 (PD-L1) Status [Up to approximately 54 months]
OS is defined as the time from randomization to death due to any cause. The OS as assessed radiographically by investigator or by histopathologic confirmation of suspected disease recurrence by CPS-determined PD-L1 status will be presented.
Disease-Free Survival (DFS) as Assessed Radiographically by Investigator or by Histopathologic Confirmation of Suspected Disease Recurrence by Tumor Mutation Burden (TMB) Status [Up to approximately 42 months]
DFS is defined as the time from randomization to the first documented local recurrence, distant metastasis, secondary systemic malignancy, or death due to any cause, whichever occurs first. The DFS as assessed radiographically by investigator or by histopathologic confirmation of suspected disease recurrence by tumor mutation burden (TMB) status, will be presented.
Overall Survival (OS) as Assessed Radiographically by Investigator or by Histopathologic Confirmation of Suspected Disease Recurrence by Tumor Mutation Burden (TMB) Status [Up to approximately 54 months]
OS is defined as the time from randomization to death due to any cause. The OS as assessed radiographically by investigator or by histopathologic confirmation of suspected disease recurrence by tumor mutation burden (TMB) status will be presented.
Number of Participants Who Experience One or More Adverse Events (AEs) [Up to approximately 54 months]
An AE is any untoward medical occurrence in a 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 will be presented.
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) [Up to approximately 52 weeks]
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be presented.
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status/Quality of Life (QoL) Score [Baseline and up to approximately 54 months]
The EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer participants. Participant responses to questions 29 ("How would you rate your overall health during the past week?") and 30 ("How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). A higher score indicates a better overall health/quality of life status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined scores will be presented.
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Physical Function Score [Baseline and up to approximately 54 months]
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=not at all to 4=very much). A higher score indicates a better quality of life. The change from baseline in physical function (EORTC QLQ-C30 Items 1-5) score will be presented.
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Symptom Specific Scale for Endometrial Cancer (EORTC QLQ-EN24) Score [Baseline and up to approximately 54 months]
The EORTC-QLQ-EN24 is a 24-item questionnaire developed to be used in conjunction with the EORTC-QLQ-C30 to assess the quality of life of endometrial cancer patients. Participant responses are scored on a 4-point scale (1=not at all to 4=very much). A higher score indicates a better quality of life. The change from baseline in EORTC QLQ-E24 score will be presented.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Has a histologically confirmed new diagnosis of Endometrial Carcinoma or

Carcinosarcoma (Mixed Mullerian Tumor) and:

Has undergone curative intent surgery that included hysterectomy and bilateral salpingo-oophorectomy; and
Is at high risk for recurrence following treatment with curative intent surgery, ie: Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) 2009 surgical stage I/II with myometrial invasion of non-endometrioid histology; FIGO 2009 surgical stage I/II with myometrial invasion of any histology with known aberrant p53 expression or p53 mutation; or FIGO (2009) surgical stage III or IVA of any histology.
Is disease-free with no evidence of loco-regional disease or distant metastasis post operatively and on imaging.
Has not received any radiation or systemic therapy, including immunotherapy, hormonal therapy, or hyperthermic intraperitoneal chemotherapy (HIPEC), in any setting including the neoadjuvant setting for endometrial cancer (EC).
Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before randomization.
Submission of a tumor tissue sample from current diagnosis of Endometrial Carcinoma or Carcinosarcoma for prospective determination of histology and mismatch repair (MMR) status by central vendor is required for all participants.
Has adequate organ function within 7 days of randomization.

Exclusion Criteria:

Has recurrent endometrial carcinoma or carcinosarcoma.
Has uterine mesenchymal tumor such as an endometrial stromal sarcoma, leiomyosarcoma, or other types of pure sarcomas. Adenosarcomas are also not allowed.
Has FIGO (2009) Surgical Stage I/II EC of endometrioid histology without a known aberrant p53 expression or p53 mutation.
Is known to have a deoxyribonucleic acid (DNA) polymerase epsilon catalytic subunit A (POLE) mutation.
Has FIGO Stage IVB disease of any histology even if there is no evidence of disease after surgery.
Has residual tumor whether measurable or non-measurable after surgery.
Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years.
Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in situ cancers.
Has received prior therapy with an anti-programmed cell death receptor 1 (PD-1), anti-programmed cell death receptor ligand 1 (PD-L1), or anti-programmed cell death receptor ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137).
Has received a live vaccine within 30 days before the first dose of study intervention.
Note: killed vaccines are allowed.
Has a known intolerance to study intervention (or any of the excipients).
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
Has any contraindication to the use of carboplatin or paclitaxel.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention.
Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, 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 history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
Has an active infection requiring systemic therapy.
Has a known history of HIV infection.
Has a known history of Hepatitis B or known active Hepatitis C virus infection.
Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
Has had an allogenic tissue/solid organ transplant.
Has not recovered adequately from surgery and/or any complications from the surgery.
Is breastfeeding.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama - Birmingham ( Site 3061)	Birmingham	Alabama	United States	35249
2	University of South Alabama, Mitchell Cancer Institute ( Site 3058)	Mobile	Alabama	United States	36604
3	HonorHealth Research Institute - Biltmore ( Site 3043)	Phoenix	Arizona	United States	85016
4	Arizona Oncology Associates PC- HOPE ( Site 3049)	Tucson	Arizona	United States	85711
5	UCSD Moores Cancer Center ( Site 3053)	La Jolla	California	United States	92093-0698
6	University Of Colorado ( Site 3051)	Aurora	Colorado	United States	80045
7	Smilow Cancer Hospital at Yale New Haven ( Site 3070)	New Haven	Connecticut	United States	06511
8	Mount Sinai Cancer Center ( Site 3081)	Miami Beach	Florida	United States	33140
9	Northside Hospital ( Site 3036)	Atlanta	Georgia	United States	30342
10	Northwestern Memorial Hospital ( Site 3044)	Chicago	Illinois	United States	60611
11	Parkview Cancer Institute ( Site 3067)	Fort Wayne	Indiana	United States	46845
12	Indiana University Melvin and Bren Simon Cancer Center ( Site 3071)	Indianapolis	Indiana	United States	46202
13	University of Iowa Hospital and Clinics ( Site 3046)	Iowa City	Iowa	United States	52242
14	Norton Cancer Institute - St. Matthews ( Site 3056)	Louisville	Kentucky	United States	40207
15	WK Physicians Network/Gynecologic Oncology Associates ( Site 3047)	Shreveport	Louisiana	United States	71103
16	University of Massachusetts Medical School ( Site 3037)	Worcester	Massachusetts	United States	01655
17	Montefiore Medical Center ( Site 3065)	Bronx	New York	United States	10461
18	Perlmutter Cancer Center at NYU Langone Hospital - Long Island ( Site 3076)	Mineola	New York	United States	11501
19	Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 3042)	New York	New York	United States	10016
20	Duke Cancer Center ( Site 3072)	Durham	North Carolina	United States	27710
21	Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 3080)	Fargo	North Dakota	United States	58102
22	OSU Wexner Medical Center ( Site 3066)	Hilliard	Ohio	United States	43026
23	Legacy Good Samaritan Medical Center ( Site 3033)	Portland	Oregon	United States	97210
24	Sidney Kimmel Cancer Center - Jefferson Health ( Site 3078)	Philadelphia	Pennsylvania	United States	19107
25	AHN West Penn Hospital ( Site 3060)	Pittsburgh	Pennsylvania	United States	15224
26	Abington Hospital - Asplundh Cancer Center ( Site 3073)	Willow Grove	Pennsylvania	United States	19090
27	Sanford Gynecology Oncology ( Site 3045)	Sioux Falls	South Dakota	United States	57104
28	UT Southwestern Medical Center ( Site 3063)	Dallas	Texas	United States	75390
29	VCU Massey Cancer Center ( Site 3068)	Richmond	Virginia	United States	23298
30	Centro de Oncología e Investigación de Buenos Aires ( Site 1005)	Berazategui	Buenos Aires	Argentina	B1884BBF
31	IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 1006)	Caba	Buenos Aires	Argentina	C1012AAR
32	Instituto de Investigaciones Clinicas Mar del Plata ( Site 1003)	Mar del Plata	Buenos Aires	Argentina	B7600FZO
33	Hospital Britanico de Buenos Aires ( Site 1002)	Buenos Aires	Caba	Argentina	C1280AEB
34	Instituto de Oncologia de Rosario ( Site 1004)	Rosario	Santa Fe	Argentina	S2000KZE
35	IDIM - Instituto de Diagnóstico e Investigaciones Metabólicas ( Site 1010)	Buenos Aires		Argentina	C1012AAR
36	Hospital Aleman ( Site 1001)	Buenos Aires		Argentina	C1118AAT
37	CEMIC ( Site 1009)	Buenos Aires		Argentina	C1431FWO
38	Centro Oncologico Riojano Integral ( Site 1007)	La Rioja		Argentina	F5300COE
39	Medizinische Universitat Graz ( Site 2004)	Graz	Steiermark	Austria	8036
40	Medizinische Universitaet Innsbruck ( Site 2001)	Innsbruck	Tirol	Austria	6020
41	Saint-Luc UCL ( Site 2042)	Bruxelles	Bruxelles-Capitale, Region De	Belgium	1200
42	C.I.U. Hopital Ambroise Pare ( Site 2039)	Mons	Hainaut	Belgium	7000
43	CHR Verviers ( Site 2035)	Verviers	Liege	Belgium	4800
44	OLV Ziekenhuis ( Site 2038)	Aalst	Oost-Vlaanderen	Belgium	9300
45	AZ Maria Middelares Gent ( Site 2032)	Gent	Oost-Vlaanderen	Belgium	9000
46	Universitair Ziekenhuis Gent ( Site 2037)	Gent	Oost-Vlaanderen	Belgium	9000
47	AZ Nikolaas ( Site 2031)	Sint-Niklaas	Oost-Vlaanderen	Belgium	9100
48	UZ Leuven ( Site 2040)	Leuven	Vlaams-Brabant	Belgium	3000
49	AZ Groeninge ( Site 2036)	Kortrijk	West-Vlaanderen	Belgium	8500
50	CHC - Groupe Sante ( Site 2041)	Liege		Belgium	4000
51	CHU Liege Sart-Tilman ( Site 2044)	Liege		Belgium	4000
52	Tom Baker Cancer Centre ( Site 3007)	Calgary	Alberta	Canada	T2N 4N2
53	Kingston Health Sciences Centre ( Site 3003)	Kingston	Ontario	Canada	K7L 2V7
54	Centre Hospitalier de l Universite de Montreal - CHUM ( Site 3006)	Montreal	Quebec	Canada	H2X 0C1
55	McGill University Health Centre ( Site 3005)	Montreal	Quebec	Canada	H4A 3J1
56	Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 3	Quebec City	Quebec	Canada	G1J 1Z4
57	Centro Investigación del Cáncer James Lind ( Site 1061)	Temuco	Araucania	Chile	4780000
58	Fundacion Arturo Lopez Perez FALP ( Site 1062)	Santiago	Region M. De Santiago	Chile	7500921
59	Centro de Cancer Nuestra Senora de la Esperanza ( Site 1063)	Santiago	Region M. De Santiago	Chile	8330032
60	Bradfordhill-Clinical Area ( Site 1070)	Santiago	Region M. De Santiago	Chile	8420383
61	Oncocentro ( Site 1065)	Vina del Mar	Valparaiso	Chile
62	Anhui Provincial Hospital-Obstetrics and Gynecology ( Site 4034)	Hefei	Anhui	China	230001
63	Beijing Cancer Hospital ( Site 4048)	Beijing	Beijing	China	100036
64	Peking Union Medical College Hospital ( Site 4036)	Beijing	Beijing	China	100730
65	Chongqing Cancer Hospital ( Site 4040)	Chongqing	Chongqing	China	400030
66	The First Affiliated Hospital of Xiamen University ( Site 4060)	Xiamen	Fujian	China	361003
67	The First Affiliated Hospital ( Site 4043)	Guangzhou	Guangdong	China	510080
68	Guangxi Medical University Affiliated Tumor Hospital ( Site 4049)	Nanning	Guangxi	China	530021
69	Harbin Medical University Cancer Hospital ( Site 4033)	Harbin	Heilongjiang	China	150081
70	Hubei Cancer Hospital ( Site 4059)	Wuhan	Hubei	China	430079
71	Xiangya Hospital Central-South University ( Site 4035)	Changsha	Hunan	China	410008
72	Hunan Cancer Hospital ( Site 4050)	Changsha	Hunan	China	410013
73	Nanjing Drum Tower Hospital ( Site 4037)	Nanjing	Jiangsu	China	210008
74	Jiangxi Maternal and Child Health Hospital ( Site 4051)	Nanchang	Jiangxi	China	530021
75	The First Bethune Hospital of Jilin University ( Site 4057)	Changchun	Jilin	China	130021
76	The First Affiliated Hospital of Xi an Jiaotong University ( Site 4045)	XI An	Shaanxi	China	710061
77	Obstetrics and Gynecology Hosp. Fudan University ( Site 4041)	Shanghai	Shanghai	China	200090
78	Shanghai Renji Hospital Affiliated to Jiao Tong University ( Site 4053)	Shanghai	Shanghai	China	200127
79	Shanghai First Maternity and Infant Hospital-Gynecology department ( Site 4001)	Shanghai	Shanghai	China	201204
80	Sichuan Cancer Hospital ( Site 4039)	Chengdu	Sichuan	China	610041
81	Tianjin Medical University Cancer Institute & Hospital ( Site 4054)	Tianjin	Tianjin	China	300060
82	Yunnan Province Cancer Hospital-Gynecology Department ( Site 4055)	Kunming	Yunnan	China	650106
83	The First Affiliated Hospital, Zhejiang University-Gynecology ( Site 4002)	Hangzhou	Zhejiang	China	310003
84	Women s Hospital School of Medicine Zhejiang University ( Site 4032)	Hangzhou	Zhejiang	China	310006
85	The First Affiliated Hospital of Wenzhou Medical University ( Site 4056)	Wenzhou	Zhejiang	China	325000
86	Clínica Vida Fundación - Sede Poblado ( Site 1096)	Medellin	Antioquia	Colombia	050030
87	Instituto Nacional de Cancerología E.S.E ( Site 1094)	Bogota	Distrito Capital De Bogota	Colombia	111511
88	Instituto Cancerologico de Narino Ltda ( Site 1092)	San Juan De Pasto	Narino	Colombia	520002
89	Fundacion Valle del Lili ( Site 1093)	Cali	Valle Del Cauca	Colombia	760032
90	Fakultní nemocnice Brno Bohunice-Gynekologicko-porodnicka klinika ( Site 2394)	Brno	Brno-mesto	Czechia	62500
91	Fakultni nemocnice Kralovske Vinohrady ( Site 2393)	Praha	Praha 10	Czechia	100 34
92	Vseobecna fakultni nemocnice v Praze ( Site 2391)	Praha	Praha 2	Czechia	120 00
93	Fakultni nemocnice Olomouc ( Site 2392)	Olomouc		Czechia	775 20
94	Rigshospitalet University Hospital ( Site 2515)	Copehagen	Hovedstaden	Denmark	2100
95	Herlev Hospital ( Site 2514)	Herlev	Hovedstaden	Denmark	2730
96	Aalborg Universitetshospital ( Site 2511)	Aalborg	Nordjylland	Denmark	9100
97	Roskilde Sygehus ( Site 2513)	Roskilde	Sjaelland	Denmark	4000
98	Odense Universitetshospital ( Site 2512)	Odense	Syddanmark	Denmark	5000
99	Tampere University Hospital ( Site 2541)	Tampere	Pirkanmaa	Finland	33520
100	Kuopio University Hospital ( Site 2543)	Kuopio	Pohjois-Savo	Finland	70029
101	Turku University Hospital ( Site 2542)	Turku	Varsinais-Suomi	Finland	20760
102	Institut De Cancerologie De Lorraine ( Site 2072)	Vandoeuvre les Nancy	Ain	France	54519
103	Centre Antoine Lacassagne ( Site 2073)	Nice	Alpes-Maritimes	France	06189
104	Centre Francois Baclesse ( Site 2062)	Caen	Calvados	France	14076
105	Hôpital Privé Des Côtes d'Armor ( Site 2063)	Plérin	Cotes-d Armor	France	22190
106	CHU Besancon - Hopital Jean Minjoz ( Site 2068)	Besancon	Doubs	France	25000
107	Institut Bergonie ( Site 2067)	Bordeaux	Gironde	France	33076
108	Institut Universitaire du Cancer Toulouse - Oncopole ( Site 2065)	Toulouse	Haute-Garonne	France	31059
109	Institut Regional du Cancer de Montpellier - ICM ( Site 2069)	Montpellier	Herault	France	34298
110	Hopital Cochin ( Site 2070)	Paris	Ile-de-France	France	75014
111	Gustave Roussy ( Site 2071)	Villejuif	Ile-de-France	France	94800
112	Hopital prive du Confluent ( Site 2061)	Nantes	Loire-Atlantique	France	44277
113	Centre Hospitalier Lyon Sud ( Site 2064)	Pierre Benite	Rhone	France	69310
114	Klinikum Ludwigsburg ( Site 2111)	Ludwigsburg	Baden-Wurttemberg	Germany	71640
115	Universitaetsklinikum Tuebingen ( Site 2113)	Tübingen	Baden-Wurttemberg	Germany	72076
116	Medizinische Hochschule Hannover-Department of Obstetrics and Gynecology ( Site 2109)	Hannover	Niedersachsen	Germany	30625
117	Universitätsklinikum Bonn-Gynaecological oncology ( Site 2103)	Bonn	Nordrhein-Westfalen	Germany	53127
118	Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung ( Site 2105)	Essen	Nordrhein-Westfalen	Germany	45136
119	Universitaetsklinikum Carl Gustav Carus Dresden-Klinik und Poliklinik für Frauenheilkunde und Gebur	Dresden	Sachsen	Germany	01307
120	Universitätsklinikum Schleswig-Holstein ( Site 2101)	Lübeck	Schleswig-Holstein	Germany	23538
121	General Hospital of Patras. St Andrews ( Site 2421)	Patras	Achaia	Greece	263 32
122	Geniko Panepistimako Nosokomeio ARETEIO ( Site 2423)	Athens	Attiki	Greece	115 28
123	Perifereiako Geniko Nosokomeio ALEXANDRA ( Site 2425)	Athens	Attiki	Greece	115 28
124	Athens University Hospital ATTIKON ( Site 2424)	Chaidari	Attiki	Greece	124 62
125	Hospital Hygeia ( Site 2426)	Marousi	Attiki	Greece	151 23
126	Euromedica General Clinic of Thessaloniki ( Site 2422)	Thessaloniki		Greece	546 45
127	Rambam Medical Center ( Site 2307)	Haifa		Israel	3109601
128	Edith Wolfson Medical Center ( Site 2306)	Holon		Israel	5822012
129	Hadassah Medical Center. Ein Kerem ( Site 2303)	Jerusalem		Israel	9112001
130	Rabin Medical Center ( Site 2305)	Petah Tikva		Israel	4941492
131	Chaim Sheba Medical Center ( Site 2301)	Ramat Gan		Israel	5262000
132	Istittuto Nazionale dei Tumori Regina Elena IRCCS - IFO ( Site 2121)	Roma	Abruzzo	Italy	00144
133	Fondazione Policlinico Universitario Agostino Gemelli ( Site 2124)	Roma	Lazio	Italy	00168
134	Istituto di Candiolo - IRCCS ( Site 2125)	Candiolo	Piemonte	Italy	10060
135	Azienda Ospedaliera Spedali Civili di Brescia ( Site 2135)	Brescia		Italy	25123
136	IRCCS Ospedale San Raffaele ( Site 2130)	Milano		Italy	20132
137	Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 2122)	Milano		Italy	20133
138	Istituto Europeo di Oncologia IRCCS-Divisione di Ginecologia Oncologica ( Site 2132)	Milano		Italy	20141
139	Azienda Ospedaliera Universitaria Federico II ( Site 2123)	Napoli		Italy	80131
140	Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 2127)	Napoli		Italy	80131
141	Istituto Oncologico Veneto IRCCS-Oncologia 2 ( Site 2134)	Padova		Italy	35128
142	Aichi Cancer Center Hospital ( Site 4190)	Nagoya	Aichi	Japan	464-8681
143	National Cancer Center Hospital East ( Site 4197)	Kashiwa	Chiba	Japan	277-8577
144	National Hospital Organization Shikoku Cancer Center ( Site 4181)	Matsuyama	Ehime	Japan	791-0280
145	Ehime University Hospital ( Site 4187)	Toon	Ehime	Japan	791-0295
146	Kurume University Hospital ( Site 4186)	Kurume	Fukuoka	Japan	830-0011
147	Gunma Prefectural Cancer Center ( Site 4183)	Ota	Gunma	Japan	373-8550
148	Hokkaido University Hospital ( Site 4194)	Sapporo	Hokkaido	Japan	060-8648
149	Hyogo Cancer Center ( Site 4195)	Akashi	Hyogo	Japan	673-8558
150	Iwate Medical University Hospital ( Site 4189)	Shiwa-gun	Iwate	Japan	028-3695
151	University of the Ryukyus Hospital ( Site 4184)	Nakagami-gun	Okinawa	Japan	903-0215
152	Saitama Medical University International Medical Center ( Site 4182)	Hidaka	Saitama	Japan	350-1298
153	Shizuoka Cancer Center Hospital and Research Institute ( Site 4192)	Sunto-gun	Shizuoka	Japan	411-8777
154	National Hospital Organization Kyushu Cancer Center ( Site 4193)	Fukuoka		Japan	811-1395
155	Niigata Cancer Center Hospital ( Site 4185)	Niigata		Japan	951-8566
156	Osaka International Cancer Institute ( Site 4188)	Osaka		Japan	5418567
157	The Cancer Institute Hospital of JFCR ( Site 4196)	Tokyo		Japan	135-8550
158	Keio University Hospital ( Site 4191)	Tokyo		Japan	160-8582
159	National Cancer Center ( Site 4065)	Goyang-si	Kyonggi-do	Korea, Republic of	10408
160	Seoul National University Bundang Hospital ( Site 4063)	Seongnam-si	Kyonggi-do	Korea, Republic of	13620
161	Severance Hospital Yonsei University Health System ( Site 4062)	Seoul		Korea, Republic of	03722
162	Asan Medical Center ( Site 4061)	Seoul		Korea, Republic of	05505
163	Samsung Medical Center ( Site 4064)	Seoul		Korea, Republic of	06351
164	Investigacion Onco Farmaceutica S de RL de CV ( Site 1127)	La Paz	Baja California Sur	Mexico	23040
165	Hospital San Lucas Cardiologica del Sureste ( Site 1122)	Tuxtla Gutierrez	Chiapas	Mexico	29090
166	Instituto Nacional de Cancerologia ( Site 1124)	Cdmx	Distrito Federal	Mexico	14080
167	Christus Muguerza Clinica Vidriera ( Site 1125)	Monterrey	Nuevo Leon	Mexico	64570
168	I Can Oncology Center SA de CV ( Site 1126)	Monterrey	Nuevo Leon	Mexico	64710
169	Hospital Angeles Roma ( Site 1123)	Ciudad de Mexico		Mexico	06700
170	Centro Oncologico Internacional. SEDNA ( Site 1121)	Mexico City		Mexico	04700
171	University Hospital of North Norway ( Site 2153)	Tromso	Troms	Norway	9019
172	Soerlandet sykehus HF Kristiansand ( Site 2152)	Kristiansand	Vest-Agder	Norway	4615
173	Oslo Universitetssykehus Radiumhospitalet ( Site 2151)	Oslo		Norway	0310
174	Mazowiecki Szpital Wojewódzki w Siedlcach-Siedleckie Centrum Onkologii ( Site 2487)	Siedlce	Mazowieckie	Poland	08-110
175	Szpital Kliniczny im Ks Anny Mazowieckiej ( Site 2481)	Warszawa	Mazowieckie	Poland	00-315
176	Bialostockie Centrum Onkologii ( Site 2483)	Bialystok	Podlaskie	Poland	15-027
177	Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 2482)	Gliwice	Slaskie	Poland	44-101
178	Swietokrzyskie Centrum Onkologii SPZOZ ( Site 2485)	Kielce	Swietokrzyskie	Poland	25-734
179	SPZOZ MSWIA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie ( Site 2486)	Olsztyn	Warminsko-mazurskie	Poland	10-228
180	Wielkopolskie Centrum Onkologii im.M.Sklodowskiej-Curie ( Site 2484)	Poznan	Wielkopolskie	Poland	61-866
181	Arkhangelsk Clinical Oncological Dispensary ( Site 2637)	Arkhangelsk	Arkhangel Skaya Oblast	Russian Federation	163045
182	Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 2645)	Ufa	Baskortostan, Respublika	Russian Federation	450054
183	Chelyabinsk Regional Clinical Center Oncology and Nuclear Medicine ( Site 2644)	Chelyabinsk	Chelyabinskaya Oblast	Russian Federation	454087
184	Krasnoyarsk Regional Clinical oncology dispensary ( Site 2643)	Krasnoyarsk	Krasnoyarskiy Kray	Russian Federation	660133
185	National Research Ogarev Mordovia State University ( Site 2648)	Saransk	Mordoviya, Respublika	Russian Federation	430032
186	FSBI National Medical Oncology Research Center n.a. N.N. Blokhina ( Site 2634)	Moscow	Moskva	Russian Federation	115478
187	Moscow Research Oncology Institute named after P.A. Hertsen ( Site 2631)	Moscow	Moskva	Russian Federation	125284
188	Nizhegorodsky Regional Oncology Dispensary-chemotherapy department (Branch№1) ( Site 2639)	Nizhniy Novgorod	Nizhegorodskaya Oblast	Russian Federation	603126
189	Samara Regional Clinical Oncology Center-Chemotherapy Dapartment ( Site 2649)	Samara	Samarskaya Oblast	Russian Federation	443031
190	Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 2636)	Saint-Petersburg	Sankt-Peterburg	Russian Federation	197758
191	Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 2646)	Kazan	Tatarstan, Respublika	Russian Federation	420029
192	Tomsk Scientific Research Institute of Oncology-Chemotherapy ( Site 2638)	Tomsk	Tomskaya Oblast	Russian Federation	634028
193	Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 2641)	Yaroslavl	Yaroslavskaya Oblast	Russian Federation	150054
194	Hospital Josep Trueta ( Site 2184)	Girona	Gerona	Spain	17007
195	Clinica Universitaria de Navarra ( Site 2181)	Madrid	Madrid, Comunidad De	Spain	28027
196	Hospital Vall D Hebron ( Site 2182)	Barcelona		Spain	08035
197	Hospital Clinic i Provincial ( Site 2185)	Barcelona		Spain	08036
198	Hospital Universitario Reina Sofia ( Site 2183)	Cordoba		Spain	14004
199	Hospital Clinico San Carlos ( Site 2187)	Madrid		Spain	28040
200	Hospital Universitario La Paz ( Site 2186)	Madrid		Spain	28046
201	Universitetssjukhuset i Linkoping. ( Site 2222)	Linkoping	Ostergotlands Lan	Sweden	581 85
202	Karolinska Universitetssjukhuset Solna ( Site 2220)	Solna	Stockholms Lan	Sweden	171 76
203	Blod-och Tumorsjukdomar ( Site 2221)	Uppsala	Uppsala Lan	Sweden	751 85
204	Changhua Christian Hospital ( Site 4095)	Changhua		Taiwan	50006
205	Taichung Veterans General Hospital ( Site 4094)	Taichung		Taiwan	40705
206	MacKay Memorial Hospital ( Site 4092)	Taipei		Taiwan	10449
207	Taipei Veterans General Hospital ( Site 4093)	Taipei		Taiwan	11217
208	Linkou Chang Gung Memorial Hospital ( Site 4091)	Taoyuan		Taiwan	333
209	Baskent Adana Dr Turgut Noyan Uygulama ve Arastirma Merkezi ( Site 2355)	Adana		Turkey	01250
210	Cukurova Uni. Tip Fakultesi ( Site 2353)	Adana		Turkey	01330
211	Baskent Universitesi Ankara Hastanesi ( Site 2354)	Ankara		Turkey	06490
212	Ankara Universitesi Tıp Fakultesi Hastanesi ( Site 2350)	Ankara		Turkey	06590
213	Medipol Universite Hastanesi ( Site 2352)	Istanbul		Turkey	34214
214	Ege University Medical Faculty ( Site 2351)	Izmir		Turkey	35100
215	Medical Park Izmir Hastanesi ( Site 2356)	Izmir		Turkey	35575
216	Chernihiv Medical Center of Modern Oncology ( Site 2368)	Chernihiv	Chernihivska Oblast	Ukraine	14029
217	Municipal Enterprise "Bukovinian сlinical oncology сenter" ( Site 2366)	Chernivtsi	Chernivetska Oblast	Ukraine	58000
218	SO Grigoriev Institute for Medical Radiology and Oncology of NAMS of Ukraine ( Site 2363)	Kharkiv	Kharkivska Oblast	Ukraine	61024
219	MNE "Khmelnytskyi regional antitumor center" ( Site 2365)	Khmelnitskyi	Khmelnytska Oblast	Ukraine	29009
220	LISOD - Israeli Oncological Hospital MedX-ray International Group, LLC ( Site 2364)	Kiev	Kyivska Oblast	Ukraine	08720
221	Lviv State Regional Oncological Center ( Site 2361)	Lviv	Lvivska Oblast	Ukraine	79031
222	The Municipal Enterprise Volyn Regional Medical Oncology Centre ( Site 2362)	Lutsk	Volynska Oblast	Ukraine	43018
223	Bristol Haematology and Oncology Centre ( Site 2244)	Bristol	Bristol, City Of	United Kingdom	BS2 8ED
224	Castle Hill Hospital-Academic Oncology ( Site 2252)	Cottingham	East Riding Of Yorkshire	United Kingdom	HU165JQ
225	Beatson West of Scotland Cancer Centre ( Site 2247)	Glasgow	Glasgow City	United Kingdom	G12 0YN
226	Leicester Royal Infirmary. Univ. Hosp. of Leicester NHS Trust ( Site 2249)	Leicester	Leicestershire	United Kingdom	LE1 5WW
227	UCLH NHS Foundation Trust ( Site 2242)	London	London, City Of	United Kingdom	NW1 2PG
228	Royal Marsden NHS Foundation Trust ( Site 2248)	London	London, City Of	United Kingdom	SW3 6JJ
229	Royal Marsden Hospital Sutton-Surrey ( Site 2241)	Sutton	Surrey	United Kingdom	SM25PT
230	The Christie Hospital NHS Foundation Trust ( Site 2243)	Manchester		United Kingdom	M20 4BX