Efficacy and Safety of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Plus Chemotherapy in Participants With Metastatic Esophageal Carcinoma (MK-7902-014/E7080-G000-320/LEAP-014)
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the efficacy and safety of pembrolizumab plus lenvatinib plus chemotherapy compared with pembrolizumab plus chemotherapy as first-line intervention in participants with metastatic esophageal carcinoma
The primary hypotheses are that pembrolizumab plus lenvatinib plus chemotherapy is superior to pembrolizumab plus chemotherapy with respect to overall survival (OS) and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
There will be 2 parts to the study: the cisplatin and 5-fluorouracil (5-FU) (FP) and paclitaxel and cisplatin (TP) Safety Run-in (Part 1) and the Main Study (Part 2). In Part 1 (FP and TP Safety Run-in), participants will be treated with pembrolizumab plus lenvatinib plus FP or TP. Dose-limiting toxicities, safety, and tolerability will be assessed.
In Part 2 (Main Study), participants (not including those participating in Part 1) will be treated with pembrolizumab plus lenvatinib plus chemotherapy or pembrolizumab plus chemotherapy. Efficacy, safety, and tolerability will be assessed.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pembrolizumab + Lenvatinib + Chemotherapy Participants receive pembrolizumab intravenously (IV) plus lenvatinib orally in combination with FP or TP in Part 1, or in combination with investigator's choice of chemotherapy with FP IV or TP IV or oxaliplatin, 5-FU and leucovorin (mFOLFOX6) IV in Part 2. Induction consists of pembrolizumab 400 mg once every 6-weeks (Q6W) for up to ~12 weeks plus lenvatinib 8 mg once daily (QD) for up to ~12 weeks plus chemotherapy with FP (cisplatin 80 mg/m^2 and 5-FU 4000 mg/m^2) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2) once every 3 weeks (Q3W) for up to ~12 weeks or mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2, and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] once every 2 weeks [Q2W] for up to ~12 weeks). This is followed by consolidation with pembrolizumab 400 mg Q6W for up to 16 cycles (each cycle = 6 weeks; total pembrolizumab treatment duration is ~2 years) plus lenvatinib 20 mg QD until progressive disease or discontinuation. |
Drug: Pembrolizumab
400 mg once every 6-week-cycle, via IV infusion.
Other Names:
Drug: Lenvatinib
8 mg QD (induction) or 20 mg QD (consolidation) via oral capsule.
Other Names:
Drug: Cisplatin
80 mg/m^2 Q3W via IV infusion, as part of investigator's choice FP chemotherapy or 75 mg/m^2 Q3W via infusion, as part of investigator's choice TP chemotherapy.
Other Names:
Drug: 5-FU
4000 mg/m^2 Q3W via IV infusion, as part of investigator's choice FP chemotherapy or 400 mg/m^2 Q2W via bolus IV infusion followed by 2400 mg/m^2 Q2W via continuous IV infusion, as part of investigator's choice mFOLFOX6 chemotherapy.
Other Names:
Drug: Oxaliplatin
85 mg/m^2 Q2W via IV infusion, as part of investigator's choice mFOLFOX6 chemotherapy.
Other Names:
Drug: Leucovorin
400 mg/m^2 Q2W as part of investigator's choice mFOLFOX6 chemotherapy.
Other Names:
Drug: Levoleucovorin
200 mg/m^2 Q2W as part of investigator's choice mFOLFOX6 chemotherapy.
Other Names:
Drug: Paclitaxel
175 mg/m^2 Q3W via IV infusion, as part of investigator's choice TP chemotherapy.
Other Names:
|
| Active Comparator: Pembrolizumab + Chemotherapy Participants receive pembrolizumab 400 mg IV Q6W for up to 18 cycles (each cycle = 6 weeks; total pembrolizumab treatment duration is ~2 years) in combination with investigator's choice of chemotherapy with FP (cisplatin 80 mg/m^2 IV Q3W for up to 6 administrations [up to ~18 weeks] and 5-FU 4000 mg/m^2 IV Q3W for up to 35 administrations [up to ~2 years]) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2 Q3W for up 6 administrations [up to ~18 weeks]) or in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2, and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] IV Q2W for up to 12 administrations [up to ~24 weeks, based on local guidance]), during Part 2. |
Drug: Pembrolizumab
400 mg once every 6-week-cycle, via IV infusion.
Other Names:
Drug: Cisplatin
80 mg/m^2 Q3W via IV infusion, as part of investigator's choice FP chemotherapy or 75 mg/m^2 Q3W via infusion, as part of investigator's choice TP chemotherapy.
Other Names:
Drug: 5-FU
4000 mg/m^2 Q3W via IV infusion, as part of investigator's choice FP chemotherapy or 400 mg/m^2 Q2W via bolus IV infusion followed by 2400 mg/m^2 Q2W via continuous IV infusion, as part of investigator's choice mFOLFOX6 chemotherapy.
Other Names:
Drug: Oxaliplatin
85 mg/m^2 Q2W via IV infusion, as part of investigator's choice mFOLFOX6 chemotherapy.
Other Names:
Drug: Leucovorin
400 mg/m^2 Q2W as part of investigator's choice mFOLFOX6 chemotherapy.
Other Names:
Drug: Levoleucovorin
200 mg/m^2 Q2W as part of investigator's choice mFOLFOX6 chemotherapy.
Other Names:
Drug: Paclitaxel
175 mg/m^2 Q3W via IV infusion, as part of investigator's choice TP chemotherapy.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Part 1 (FP and TP Safety Run-in): Number of Participants With Dose Limiting Toxicities (DLTs) [Up to ~21 days]
Hematologic DLTs are defined as Grade 4 neutropenia lasting for ≥7 days, Grade 3 or Grade 4 febrile neutropenia, Grade 3 thrombocytopenia with bleeding, Grade 4 thrombocytopenia, or Grade 4 anemia. Other nonhematologic toxicities considered a DLT include any other Grade 4 or Grade 5 toxicity, Grade 3 toxicities lasting >3 days (excluding nausea, vomiting, and diarrhea controlled by medical intervention within 72 hours, and Grade 3 rash in the absence of desquamation with no mucosal involvement), Grade 3 hypertension not able to be controlled by medication, ≥Grade 3 gastrointestinal perforation, ≥Grade 3 wound dehiscence requiring medical or surgical intervention, any grade thromboembolic event or any Grade 3 nonhematologic laboratory value requiring medical intervention or hospitalization. The number of participants in Part 1 with DLTs will be presented.
- Part 1 (FP and TP Safety Run-in): Number of Participants With Adverse Events (AEs) [Up to ~51 months]
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants in Part 1 with AEs will be presented.
- Part 1 (FP and TP Safety Run-in): Number of Participants who Discontinued Study Treatment Due to an AE [Up to ~51 months]
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants in Part 1 who discontinue study treatment due to an AE will be presented.
- Part 2 (Main Study): Overall Survival (OS) in all Participants [Up to ~49 months]
OS is defined as the time from randomization to death due to any cause. OS in Part 2 for all randomized participants will be presented.
- Part 2 (Main Study): Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in all Participants [Up to ~41 months]
PFS is defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 has been adjusted to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. PFS in Part 2 for all randomized participants will be presented.
Secondary Outcome Measures
- Part 2 (Main Study): Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR in all Participants [Up to ~34 months]
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions), per RECIST 1.1 adjusted to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, as assessed by BICR. ORR in Part 2 for all randomized participants will be presented.
- Part 2 (Main Study): Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR in all Participants [Up to ~34 months]
For participants who demonstrate a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), per RECIST 1.1 by BICR, DOR is defined as the time from first documented evidence of CR or PR until PD or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 has been adjusted to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. DOR in Part 2 for all randomized participants will be presented.
- Part 2 (Main Study): OS in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10 [Up to ~49 months]
OS is defined as the time from randomization to death due to any cause. OS in Part 2 for randomized participants with PD-L1 CPS ≥10 will be presented.
- Part 2 (Main Study): PFS per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10 [Up to ~41 months]
PFS is defined as the time from randomization to the first documented PD per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 has been adjusted to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. PFS in Part 2 for randomized participants with PD-L1 CPS ≥10 will be presented.
- Part 2 (Main Study): ORR per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10 [Up to ~34 months]
ORR is defined as the percentage of participants with CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), per RECIST 1.1 adjusted to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, as assessed by BICR. ORR in Part 2 for randomized participants with PD-L1 CPS ≥10 will be presented.
- Part 2 (Main Study): DOR per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10 [Up to ~34 months]
For participants who demonstrate a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), per RECIST 1.1 by BICR, DOR is defined as the time from first documented evidence of CR or PR until PD or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 has been adjusted to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. DOR in Part 2 for randomized participants with PD-L1 CPS ≥10 will be presented.
- Part 2 (Main Study): Number of Participants With AEs [Up to ~49 months]
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants in Part 2 with AEs will be presented.
- Part 2 (Main Study): Number of Participants who Discontinued Study Treatment Due to an AE [Up to ~49 months]
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants in Part 2 who discontinue study treatment due to an AE will be presented.
- Part 2 (Main Study): Change From Baseline in Health-related Quality of life (HRQoL) Score Using European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) [Baseline and ~24 months]
The EORTC QLQ-C30 is a questionnaire to assess the overall HRQoL. Participant responses to the question " How would you rate your overall quality of life (QoL) during the past week?" are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall QoL. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in HRQoL EORTC QLQ-C30 score in participants in Part 2 will be presented.
- Part 2 (Main Study): Change From Baseline in HRQoL Score Using EORTC Quality of Life Questionnaire-Oesophageal Module (QLQ-OES18) [Baseline and ~24 months]
The EORTC QLQ-OES18 is a disease-specific questionnaire to assess measurements specific to esophageal cancer. It contains 18 items and is based on four subscales-dysphagia, eating, reflux and pain. All items are scored using a four-point scale that offers these response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. A higher score indicates worse level of symptoms. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in HRQoL QLQ-OES18 score in participants in Part 2 will be presented.
- Part 2 (Main Study): Time to Deterioration (TTD) in HRQoL Score Using EORTC QLQ-C30 [Up to ~ 24 months]
TTD is defined as the time from baseline to the first onset of a ≥10-point change from baseline in the HRQoL EORTC QLQ-C30 score. The EORTC QLQ-C30 is a questionnaire to assess the overall HRQoL. Participant responses to the question " How would you rate your overall QoL during the past week?" are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall QoL. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A longer TTD indicates a better outcome. The TTD in HRQoL EORTC QLQ-C30 score in participants in Part 2 will be presented.
- Part 2 (Main Study): TTD in HRQoL Score Using EORTC QLQ-OES18 [Up to ~ 24 months]
TTD is defined as the time from baseline to the first onset of a ≥10-point change from baseline in the HRQoL EORTC QLQ-OES18 score. The EORTC QLQ-OES18 is a disease-specific questionnaire to assess measurements specific to esophageal cancer. It contains 18 items and is based on four subscales-dysphagia, eating, reflux and pain. All items are scored using a four-point scale that offers these response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. A higher score indicates worse level of symptoms. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A longer TTD indicates a better outcome. The TTD in HRQoL QLQ-OES18 score in participants in Part 2 will be presented.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Has a histologically or cytologically confirmed diagnosis of metastatic squamous cell carcinoma of the esophagus
-
Male participants are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 7 days after the last dose of lenvatinib or 90 days after the last dose of chemotherapy, whichever comes last; 7 days after lenvatinib is stopped, if the participant is on pembrolizumab only and is greater than 90 days post chemotherapy, no male contraception is needed
-
Female participant is not pregnant or breastfeeding and is not a woman of childbearing potential (WOCBP) or is a WOCBP using a contraceptive method that is highly effective or is abstinent from heterosexual intercourse as their preferred and usual lifestyle during the intervention period and for at least 120 days after the last dose of pembrolizumab, 30 days after the last dose of lenvatinib, or 180 days after the last dose of chemotherapy, whichever occurs last, and agrees not to donate eggs during this period
-
Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP≤150/90 millimeters of mercury (mm Hg) with no change in antihypertensive medications within 1 week prior to randomization
-
Has adequate organ function
Exclusion Criteria:
-
Has had previous therapy for locally advanced unresectable or metastatic esophageal cancer
-
Has locally advanced esophageal carcinoma
-
Has metastatic adenocarcinoma of the esophagus
-
Has direct invasion into adjacent organs such as the aorta or trachea
-
Has radiographic evidence of encasement of a major blood vessel, or of intratumoral cavitation
-
Has perforation risks or significant gastrointestinal (GI) bleeding
-
Has had clinically significant hemoptysis within 3 weeks prior to the first dose of study drug or tumor bleeding within 2 weeks prior to the first dose of study intervention
-
Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention
-
Has GI obstruction, poor oral intake, difficulty in taking oral medication, or existing esophageal stent
-
Has had major surgery, open biopsy, or significant traumatic injury within 3 weeks prior to first dose of study interventions
-
Has received prior radiotherapy within 2 weeks of start of study intervention or have had a history of radiation pneumonitis
-
Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention; administration of killed vaccines is allowed
-
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any form of immunosuppressive therapy within 7 days prior to the first dose of study intervention, or has a history of organ transplant, including allogeneic stem cell transplant
-
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
-
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
-
Has an active autoimmune disease that has required systemic treatment in past 2 years; replacement therapy is not considered a form of systemic treatment and is allowed
-
Has a history of non-infectious pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease
-
Has poorly controlled diarrhea
-
Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
-
Has peripheral neuropathy ≥Grade 2
-
Has a known history of human immunodeficiency virus (HIV) infection
-
Has a known history of Hepatitis B or know active Hepatitis C virus infection
-
Has a weight loss of >20% within the last 3 months
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | City of Hope ( Site 0102) | Duarte | California | United States | 91010 |
| 2 | James Graham Brown Cancer Center ( Site 0117) | Louisville | Kentucky | United States | 40202 |
| 3 | Norton Cancer Institute ( Site 0116) | Louisville | Kentucky | United States | 40217 |
| 4 | Johns Hopkins Bayview Medical Center ( Site 0152) | Baltimore | Maryland | United States | 21224 |
| 5 | UMASS Memorial Medical Center ( Site 0120) | Worcester | Massachusetts | United States | 01655 |
| 6 | Weill Cornell Medical College ( Site 0133) | New York | New York | United States | 10065 |
| 7 | Seattle Cancer Care Alliance ( Site 0145) | Seattle | Washington | United States | 98109 |
| 8 | Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 0203) | Berazategui | Buenos Aires | Argentina | B1884BBF |
| 9 | IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 0202) | Caba | Buenos Aires | Argentina | C1012AAR |
| 10 | Instituto de Investigaciones Clinicas Mar del Plata ( Site 0205) | Mar del Plata | Buenos Aires | Argentina | B7600FZO |
| 11 | Sanatorio Parque ( Site 0206) | Rosario | Santa Fe | Argentina | S2000DSV |
| 12 | Fundacion Favaloro ( Site 0201) | Buenos Aires | Argentina | C1093AAS | |
| 13 | Instituto San Marcos ( Site 0213) | San Juan | Argentina | J5400EBB | |
| 14 | James Lind Centro de Investigación del Cáncer ( Site 0412) | Temuco | Araucania | Chile | 4780000 |
| 15 | Centro de Investigacion y desarrollo Oncologico SpA - CIDO SpA ( Site 0401) | Temuco | Araucania | Chile | 4810218 |
| 16 | Fundacion Arturo Lopez Perez FALP ( Site 0403) | Santiago | Region M. De Santiago | Chile | 7500836 |
| 17 | Oncovida ( Site 0413) | Santiago | Region M. De Santiago | Chile | 7510032 |
| 18 | Clínica San Carlos de Apoquindo Red Salud UC Christus ( Site 0407) | Santiago | Region M. De Santiago | Chile | 7550000 |
| 19 | Bradford Hill Centro de Investigaciones Clinicas ( Site 0404) | Santiago | Region M. De Santiago | Chile | 8420383 |
| 20 | The Second Affiliated Hospital of Anhui Medical University ( Site 8026) | Hefei | Anhui | China | 230031 |
| 21 | Beijing Cancer Hospital ( Site 8001) | Beijing | Beijing | China | 100142 |
| 22 | Fujian Provincial Cancer Hospital ( Site 8029) | Fuzhou | Fujian | China | 350014 |
| 23 | Zhongshan Hospital Affiliated to Xiamen University ( Site 8055) | Xiamen | Fujian | China | 361004 |
| 24 | The First Affiliated Hospital.Sun Yat-sen University ( Site 8047) | Guangzhou | Guangdong | China | 510080 |
| 25 | Southern Medical University Nanfang Hospital ( Site 8031) | Guangzhou | Guangdong | China | 510515 |
| 26 | The Third Xiangya Hospital of Central South University ( Site 8046) | Changsha | Hainan | China | 410013 |
| 27 | The First Affiliated Hospital of Hainan Medical University ( Site 8042) | Haikou | Hainan | China | 570102 |
| 28 | Affiliated Hospital of Chengde Medical Univeristy ( Site 8053) | Chengde | Hebei | China | 067055 |
| 29 | Harbin Medical University Cancer Hospital ( Site 8009) | Harbin | Heilongjiang | China | |
| 30 | Anyang Cancer Hospital ( Site 8006) | Anyang | Henan | China | 455000 |
| 31 | The First Affiliated Hospital of Xinxiang Medical University ( Site 8018) | Xinxiang | Henan | China | 453100 |
| 32 | Affiliated hospital of Jiangnan university ( Site 8049) | Wuxi | Jiangsu | China | 214122 |
| 33 | The Affiliated Hospital of Xuzhou Medical University ( Site 8015) | Xuzhou | Jiangsu | China | 221000 |
| 34 | Jilin Cancer Hospital ( Site 8016) | Changchun | Jilin | China | 130012 |
| 35 | Jinan Central Hospital ( Site 8052) | Jinan | Shandong | China | 250013 |
| 36 | Affiliated Hospital of Jining Medical University ( Site 8017) | Jining | Shandong | China | 272000 |
| 37 | Linyi Cancer Hospital- Medical Oncology Department ( Site 8051) | Linyi | Shandong | China | 276000 |
| 38 | Shanxi Provincial Cancer Hospital ( Site 8019) | Taiyuan | Shanxi | China | 030013 |
| 39 | West China Hospital of Sichuan University ( Site 8048) | Chengdu | Sichuan | China | 610041 |
| 40 | Tianjin Medical University Cancer Institute & Hospital ( Site 8035) | Tianjin | Tianjin | China | 300060 |
| 41 | Cancer Hospital Affiliated to Xinjiang Medical University ( Site 8041) | Urumqi | Xinjiang | China | 830000 |
| 42 | Sir Run Run Shaw Hospital ( Site 8021) | Hangzhou | Zhejiang | China | 310016 |
| 43 | CIMCA Centro de Investigacion y Manejo del Cancer ( Site 0902) | San Jose | Costa Rica | 10103 | |
| 44 | Onco Tech S A ( Site 0901) | San Jose | Costa Rica | 10103 | |
| 45 | Rigshospitalet ( Site 2102) | Copenhagen | Hovedstaden | Denmark | 2100 |
| 46 | Odense University Hospital ( Site 2101) | Odense | Syddanmark | Denmark | 5000 |
| 47 | Institut De Cancerologie De Lorraine ( Site 1010) | Vandoeuvre les Nancy | Ain | France | 54519 |
| 48 | Centre Hospitalier Régional Universitaire de Brest - Hôpital-Institut de cancérologie et hématologi | Brest | Bretagne | France | 29200 |
| 49 | Centre Georges Francois Leclerc ( Site 1008) | Dijon | Cote-d Or | France | 21000 |
| 50 | CHU Bordeaux Haut-Leveque ( Site 1012) | Pessac | Gironde | France | 33604 |
| 51 | Institut du Cancer de Montpellier ( Site 1002) | Montpellier | Herault | France | 34298 |
| 52 | CHRU de Tours - Hopital Bretonneau ( Site 1018) | Tours | Indre-et-Loire | France | 37044 |
| 53 | Institut De Cancerologie De L Ouest ( Site 1003) | Saint Herblain | Loire-Atlantique | France | 44805 |
| 54 | Hôpital Claude Huriez ( Site 1030) | Lille | Nord | France | 59000 |
| 55 | Hopital Henri Mondor ( Site 1007) | Creteil | Val-de-Marne | France | 94010 |
| 56 | Hopital Saint Louis ( Site 1029) | Paris | France | 75010 | |
| 57 | Centro Regional de Sub Especialidades Medicas SA ( Site 0604) | Guatemala | Quetzaltenango | Guatemala | 09001 |
| 58 | Oncomedica ( Site 0602) | Guatemala | Guatemala | 01010 | |
| 59 | Soluciones Gastrointestinales S.A. ( Site 0607) | Guatemala | Guatemala | 01010 | |
| 60 | Medi-K Cayala ( Site 0601) | Guatemala | Guatemala | 01016 | |
| 61 | Queen Mary Hospital ( Site 4001) | Hong Kong | Hong Kong | ||
| 62 | Queen Elizabeth Hospital. ( Site 4004) | Kowloon | Hong Kong | ||
| 63 | Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 1203) | Szolnok | Jasz-Nagykun-Szolnok | Hungary | 5000 |
| 64 | Orszagos Onkologiai Intezet ( Site 1207) | Budapest | Hungary | 1122 | |
| 65 | Humanitas Research Hospital ( Site 1309) | Rozzano | Lombardia | Italy | 20089 |
| 66 | Azienda Ospedaliero Universitaria Careggi ( Site 1301) | Firenze | Italy | 50134 | |
| 67 | IRCCS Ospedale San Raffaele di Milano ( Site 1304) | Milano | Italy | 20132 | |
| 68 | Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 1306) | Milano | Italy | 20133 | |
| 69 | A.O. Universitaria di Modena ( Site 1307) | Modena | Italy | 41124 | |
| 70 | A.O.U. Universita degli Studi della Campania-Luigi Vanvitelli ( Site 1305) | Napoli | Italy | 80131 | |
| 71 | Universita Cattolica del Sacro Cuore - Policlinico Gemelli ( Site 1310) | Roma | Italy | 00168 | |
| 72 | A.O.U. Santa Maria della Misericordia di Udine ( Site 1302) | Udine | Italy | 33100 | |
| 73 | National Cancer Center Hospital East ( Site 9002) | Kashiwa | Chiba | Japan | 277-8577 |
| 74 | National Hospital Organization Shikoku Cancer Center ( Site 9019) | Matsuyama | Ehime | Japan | 791-0280 |
| 75 | Hyogo Cancer Center ( Site 9014) | Akashi | Hyogo | Japan | 673-8558 |
| 76 | Ibaraki Prefectural Central Hospital ( Site 9007) | Kasama | Ibaraki | Japan | 309-1793 |
| 77 | Kagawa University Hospital ( Site 9015) | Kita | Kagawa | Japan | 761-0701 |
| 78 | Kanagawa Cancer Center ( Site 9004) | Yokohama | Kanagawa | Japan | 241-8515 |
| 79 | Tohoku University Hospital ( Site 9013) | Sendai-shi | Miyagi | Japan | 980-8574 |
| 80 | Kindai University Hospital- Osakasayama Campus ( Site 9017) | Osaka-sayama | Osaka | Japan | 589-8511 |
| 81 | Osaka Medical and Pharmaceutical University Hospital ( Site 9008) | Takatsuki | Osaka | Japan | 569-8686 |
| 82 | Saitama Cancer Center ( Site 9003) | Kitaadachi-gun | Saitama | Japan | 362-0806 |
| 83 | Shizuoka Cancer Center ( Site 9016) | Nagaizumi | Shizuoka | Japan | 411-8777 |
| 84 | National Hospital Organization Kyushu Cancer Center ( Site 9010) | Fukuoka | Japan | 811-1395 | |
| 85 | Kyoto University Hospital ( Site 9011) | Kyoto | Japan | 606-8507 | |
| 86 | Osaka International Cancer Institute ( Site 9009) | Osaka | Japan | 541-8567 | |
| 87 | Osaka General Medical Center ( Site 9018) | Osaka | Japan | 558-8558 | |
| 88 | National Cancer Center Hospital ( Site 9001) | Tokyo | Japan | 104-0045 | |
| 89 | The Cancer Institute Hospital of JFCR ( Site 9005) | Tokyo | Japan | 135-8550 | |
| 90 | Keio university hospital ( Site 9020) | Tokyo | Japan | 160-8582 | |
| 91 | Seoul National University Bundang Hospital ( Site 5006) | Seongnam-si | Kyonggi-do | Korea, Republic of | 13605 |
| 92 | Asan Medical Center ( Site 5002) | Songpagu | Seoul | Korea, Republic of | 05505 |
| 93 | Severance Hospital ( Site 5003) | Seoul | Korea, Republic of | 03722 | |
| 94 | Samsung Medical Center ( Site 5005) | Seoul | Korea, Republic of | 06351 | |
| 95 | Korea University Guro Hospital ( Site 5001) | Seoul | Korea, Republic of | 08308 | |
| 96 | Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1507) | Ufa | Baskortostan, Respublika | Russian Federation | 450054 |
| 97 | FSBI National Medical Oncology Research Center n.a. N.N. Blokhina ( Site 1510) | Moscow | Moskva | Russian Federation | 115478 |
| 98 | SBHI Leningrad Regional Oncology Dispensary ( Site 1502) | Saint Petersburg | Sankt-Peterburg | Russian Federation | 188663 |
| 99 | Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1503) | Saint Petersburg | Sankt-Peterburg | Russian Federation | 197758 |
| 100 | Academician I.P. Pavlov First St. Petersburg State Medical University ( Site 1519) | Saint-Petersburg | Sankt-Peterburg | Russian Federation | 197022 |
| 101 | Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1509) | Kazan | Tatarstan, Respublika | Russian Federation | 420029 |
| 102 | SAIH of Tyumen reg "Multifield clinical medical center "Medical city" ( Site 1520) | Tyumen | Tyumenskaya Oblast | Russian Federation | 625041 |
| 103 | Hospital Universitario General de Asturias ( Site 1601) | Oviedo | Asturias | Spain | 33011 |
| 104 | Hospital Universitario Marques de Valdecilla ( Site 1602) | Santander | Cantabria | Spain | 39008 |
| 105 | Hospital General Universitari Vall d Hebron ( Site 1607) | Barcelona | Spain | 08035 | |
| 106 | Hospital General Universitario Gregorio Maranon ( Site 1604) | Madrid | Spain | 28009 | |
| 107 | Hospital Virgen del Rocio ( Site 1606) | Sevilla | Spain | 41013 | |
| 108 | Chang Gung Med Foundation. Kaohsiung Branch ( Site 6005) | Kaohsiung | Taiwan | 83301 | |
| 109 | China Medical University Hospital ( Site 6003) | Taichung | Taiwan | 40447 | |
| 110 | National Cheng Kung University Hospital ( Site 6004) | Tainan | Taiwan | 704 | |
| 111 | National Taiwan University Hospital ( Site 6001) | Taipei | Taiwan | 10002 | |
| 112 | Taipei Veterans General Hospital ( Site 6006) | Taipei | Taiwan | 11217 | |
| 113 | Medeniyet Universitesi Tip Fakultesi ( Site 1703) | Istambul | Istanbul | Turkey | 34732 |
| 114 | Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1701) | Ankara | Turkey | 06230 | |
| 115 | Memorial Ankara Hastanesi ( Site 1702) | Ankara | Turkey | 06520 | |
| 116 | Ataturk Universitesi Tip Fakultesi Hastanesi ( Site 1712) | Erzurum | Turkey | 25240 | |
| 117 | Istanbul Okmeydanı Egitim ve Arastirma Hastanesi ( Site 1711) | Istanbul | Turkey | 34384 | |
| 118 | Chernihiv Medical Center of Modern Oncology ( Site 1811) | Chernihiv | Chernihivska Oblast | Ukraine | 14029 |
| 119 | MI Kryvyi Rih Oncology Dispensary of Dnipropetrovsk Regional Council ( Site 1804) | Kryviy Rih | Dnipropetrovska Oblast | Ukraine | 50048 |
| 120 | Kharkiv Regional Clinical Oncology Center ( Site 1812) | Kharkiv | Kharkivska Oblast | Ukraine | 61000 |
| 121 | Institute of General and Emergency Surgery n.a Zaitsev NAMS of Ukraine ( Site 1813) | Kharkiv | Kharkivska Oblast | Ukraine | 61103 |
| 122 | Communal nonprofit enterprise "Kherson Regional Oncology Dispensary" of Kherson Regional Council ( | Antonivka Village | Khersonska Oblast | Ukraine | 73000 |
| 123 | National Cancer Institute of the MoH of Ukraine ( Site 1806) | Kyiv | Kyivska Oblast | Ukraine | 03022 |
| 124 | Podillya Regional Center of Oncology ( Site 1809) | Vinnytsia | Vinnytska Oblast | Ukraine | 21029 |
| 125 | Volyn Regional Oncological Dispensary ( Site 1816) | Lutsk | Volynska Oblast | Ukraine | 43018 |
| 126 | Ninewells Hospital and Medical School ( Site 1907) | Dundee | Angus | United Kingdom | DD1 9SY |
| 127 | Cambridge University Hospitals NHSFT ( Site 1908) | Cambridge | Cambridgeshire | United Kingdom | CB2 2QQ |
| 128 | Western General Hospital ( Site 1912) | Edinburgh | Edinburgh, City Of | United Kingdom | EH4 2XU |
| 129 | Nottingham University Hospital NHS Trust ( Site 1910) | Nottingham | England | United Kingdom | ng5 1pb |
| 130 | University College London Hospitals NHS Foundation Trust ( Site 1901) | London | London, City Of | United Kingdom | NW1 2BU |
| 131 | The Christie NHS Foundation Trust ( Site 1909) | Manchester | United Kingdom | M20 4BX |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
- Eisai Inc.
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 7902-014
- MK-7902-014
- LEAP-014
- E7080-G000-320
- jRCT2031210231
- 2020-001911-26