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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT03189719
Registration number
NCT03189719
Ethics application status
Date submitted
14/06/2017
Date registered
16/06/2017
Date last updated
2/05/2024
Titles & IDs
Public title
First-line Esophageal Carcinoma Study With Pembrolizumab Plus Chemo vs. Chemo (MK-3475-590/KEYNOTE-590)
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Scientific title
A Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial of Pembrolizumab (MK-3475) in Combination With Cisplatin and 5-Fluorouracil Versus Placebo in Combination With Cisplatin and 5-Fluorouracil as First-Line Treatment in Subjects With Advanced/Metastatic Esophageal Carcinoma (KEYNOTE-590)
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Secondary ID [1]
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173739
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Secondary ID [2]
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3475-590
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Esophageal Neoplasms
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Condition category
Condition code
Cancer
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Oesophageal (gullet)
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Other interventions - Pembrolizumab
Treatment: Drugs - Placebo
Treatment: Drugs - Cisplatin
Treatment: Drugs - 5-FU
Experimental: Pembrolizumab + SOC - Participants receive pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) plus standard of care (SOC) chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments will be administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Placebo Comparator: Placebo + SOC - Participants receive placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments will be administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Other interventions: Pembrolizumab
200 mg administered IV Q3W on Day 1 of each 3-week cycle, up to 35 administrations.
Treatment: Drugs: Placebo
Placebo to pembrolizumab (saline) administered IV Q3W on Day 1 of each 3-week cycle, up to 35 administrations.
Treatment: Drugs: Cisplatin
80 mg/m^2 administered IV Q3W on Day 1 of each 3-week cycle. Duration of cisplatin treatment will be capped at 6 doses.
Treatment: Drugs: 5-FU
800 mg/m^2/day (4000 mg/m^2 total per cycle) administered as continuous IV infusion on Days 1 to 5 (120 hours) of each 3-week cycle, or per local standard for 5-FU administration, up to 35 administrations.
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Intervention code [1]
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Other interventions
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Intervention code [2]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Overall Survival (OS) in Participants With Esophageal Squamous Cell Carcinoma (ESCC) Whose Tumors Are Programmed Cell Death-Ligand 1 (PD-L1) Biomarker-Positive (Combined Positive Score [CPS] =10)
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Assessment method [1]
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Overall survival was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS is reported here for all participants of the Intent-To-Treat (ITT) population (all randomized) who had ESCC and who were PD-L1 CPS =10.
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Timepoint [1]
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Up to approximately 34 months
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Primary outcome [2]
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OS in Participants With ESCC
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Assessment method [2]
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Overall survival was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS is reported here for all participants of the ITT population (all randomized) who had ESCC.
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Timepoint [2]
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Up to approximately 34 months
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Primary outcome [3]
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OS in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS =10)
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Assessment method [3]
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Overall survival was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS is reported here for all participants of the ITT population (all randomized) who were PD-L1 CPS =10.
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Timepoint [3]
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Up to approximately 34 months
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Primary outcome [4]
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OS in All Participants
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Assessment method [4]
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Overall survival was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS is reported here for all participants of the ITT population (all randomized).
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Timepoint [4]
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Up to approximately 34 months
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Primary outcome [5]
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Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) As Assessed By Investigator in Participants With ESCC
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Assessment method [5]
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PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, PFS is reported here for all participants of the ITT population (all randomized) who had ESCC.
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Timepoint [5]
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0
Up to approximately 34 months
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Primary outcome [6]
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PFS Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS =10)
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Assessment method [6]
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PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, PFS is reported here for all participants of the ITT population (all randomized) who were PD-L1 CPS =10.
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Timepoint [6]
0
0
Up to approximately 34 months
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Primary outcome [7]
0
0
PFS Per RECIST 1.1 As Assessed By Investigator in All Participants
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Assessment method [7]
0
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PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, PFS is reported here for all participants of the ITT population (all randomized) who were PD-L1 CPS =10.
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Timepoint [7]
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Up to approximately 34 months
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Secondary outcome [1]
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Objective Response Rate (ORR) Per RECIST 1.1 As Assessed By Investigator in All Participants
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Assessment method [1]
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ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: =30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for all participants of the ITT population (all randomized).
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Timepoint [1]
0
0
Up to approximately 34 months
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Secondary outcome [2]
0
0
ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS =10)
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Assessment method [2]
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0
ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: =30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for all participants of the ITT population (all randomized) who had ESCC and who were PD-L1 CPS =10.
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Timepoint [2]
0
0
Up to approximately 34 months
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Secondary outcome [3]
0
0
ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC
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Assessment method [3]
0
0
ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: =30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for all participants of the ITT population (all randomized) who had ESCC.
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Timepoint [3]
0
0
Up to approximately 34 months
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Secondary outcome [4]
0
0
ORR Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS =10)
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Assessment method [4]
0
0
ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: =30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for all participants of the ITT population (all randomized) who were PD-L1 CPS =10.
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Timepoint [4]
0
0
Up to approximately 34 months
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Secondary outcome [5]
0
0
Duration of Response (DOR) Per RECIST 1.1 As Assessed By Investigator in All Participants
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Assessment method [5]
0
0
For participants who demonstrated 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 as assessed by the investigator, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death due to any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was 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 had to demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR is reported here for all participants of the ITT population (all randomized) who had CR or PR.
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Timepoint [5]
0
0
Up to approximately 34 months
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Secondary outcome [6]
0
0
DOR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS =10)
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Assessment method [6]
0
0
For participants who demonstrated 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 as assessed by the investigator, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death due to any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was 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 had to demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR is reported here for all participants of the ITT population (all randomized) who had CR or PR, and who had ESCC and were PD-L1 CPS =10.
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Timepoint [6]
0
0
Up to approximately 34 months
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Secondary outcome [7]
0
0
DOR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC
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Assessment method [7]
0
0
For participants who demonstrated 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 as assessed by the investigator, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death due to any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was 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 had to demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR is reported here for all participants of the ITT population (all randomized) who had CR or PR, and who had ESCC.
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Timepoint [7]
0
0
Up to approximately 34 months
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Secondary outcome [8]
0
0
DOR Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS =10)
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Assessment method [8]
0
0
For participants who demonstrated 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 as assessed by the investigator, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death due to any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was 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 had to demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR is reported here for all participants of the ITT population (all randomized) who had CR or PR, and were PD-L1 CPS =10.
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Timepoint [8]
0
0
Up to approximately 34 months
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Secondary outcome [9]
0
0
Number of Participants With an Adverse Event (AE)
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Assessment method [9]
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An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that experienced at least one AE was reported for each treatment arm.
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Timepoint [9]
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Up to approximately 28 months
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Secondary outcome [10]
0
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Number of Participants Discontinuing Study Treatment Due to an AE
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Assessment method [10]
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0
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that discontinued any study drug due to an AE was reported for each treatment arm.
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Timepoint [10]
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Up to approximately 27 months
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Secondary outcome [11]
0
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Change From Baseline To Week 18 in the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) Combined Score in All Participants
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Assessment method [11]
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The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the Quality of Life (QoL) question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was reported by treatment arm as a pre-specified secondary analysis for all participants.
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Timepoint [11]
0
0
Baseline, Week 18
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Secondary outcome [12]
0
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Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS =10)
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Assessment method [12]
0
0
The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the Quality of Life (QoL) question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was reported by treatment arm as a pre-specified secondary analysis for all participants who had ESCC and who were PD-L1 CPS =10.
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Timepoint [12]
0
0
Baseline, Week 18
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Secondary outcome [13]
0
0
Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants With ESCC
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Assessment method [13]
0
0
The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the Quality of Life (QoL) question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was reported by treatment arm as a pre-specified secondary analysis for all participants who had ESCC.
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Timepoint [13]
0
0
Baseline, Week 18
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Secondary outcome [14]
0
0
Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS =10)
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Assessment method [14]
0
0
The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the Quality of Life (QoL) question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was reported by treatment arm as a pre-specified secondary analysis for all participants who were PD-L1 CPS =10.
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Timepoint [14]
0
0
Baseline, Week 18
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Secondary outcome [15]
0
0
Change From Baseline in the EORTC Quality Of Life Questionnaire Oesophageal Module (QLQ-OES18) Subscale Scores in All Participants
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Assessment method [15]
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0
The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. For the purposes of this study, the Dysphagia subscale (three items), Pain subscale (three items), and Reflux subscale (two items) were evaluated. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores represent a higher ("worse") level of symptoms. Per protocol, change from baseline to Week 18 in the Dysphagia, Pain, and Reflux subscales was reported for all participants in each treatment arm. Negative changes from baseline indicate a decrease in symptom severity.
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Timepoint [15]
0
0
Baseline, Week 18
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Secondary outcome [16]
0
0
Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS =10)
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Assessment method [16]
0
0
The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. For the purposes of this study, the Dysphagia subscale (three items), Pain subscale (three items), and Reflux subscale (two items) were evaluated. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores representing a higher ("worse") level of symptoms. Change from baseline to Week 18 in the Dysphagia, Pain, and Reflux subscales was reported for participants with ESCC who were PD-L1 CPS=10 in each treatment arm. Negative changes from baseline indicate a decrease in symptom severity.
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Timepoint [16]
0
0
Baseline, Week 18
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Secondary outcome [17]
0
0
Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC
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Assessment method [17]
0
0
The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. For the purposes of this study, the Dysphagia subscale (three items), Pain subscale (three items), and Reflux subscale (two items) were evaluated. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores representing a higher ("worse") level of symptoms. Change from baseline to Week 18 in the Dysphagia, Pain, and Reflux subscales was reported for participants with ESCC in each treatment arm. Negative changes from baseline indicate a decrease in symptom severity.
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Timepoint [17]
0
0
Baseline, Week 18
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Secondary outcome [18]
0
0
Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS =10)
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Assessment method [18]
0
0
The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. For the purposes of this study, the Dysphagia subscale (three items), Pain subscale (three items), and Reflux subscale (two items) were evaluated. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores representing a higher ("worse") level of symptoms. Change from baseline to Week 18 in the Dysphagia, Pain, and Reflux subscales was reported for participants who were PD-L1 CPS=10 in each treatment arm. Negative changes from baseline indicate a decrease in symptom severity.
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Timepoint [18]
0
0
Baseline, Week 18
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Eligibility
Key inclusion criteria
- Has histologically- or cytologically-confirmed diagnosis of locally advanced
unresectable or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus
or advanced/metastatic Siewert type 1 adenocarcinoma of the esophagogastric junction
(EGJ)
- Has measurable disease per RECIST 1.1 as determined by the local site
investigator/radiology assessment
- Eastern Cooperative Group (ECOG) performance status of 0 to 1
- Can provide either a newly obtained or archival tissue sample for PD-L1 by
immunohistochemistry analysis
- Female participants of childbearing potential must have a negative urine or serum
pregnancy test within 72 hours prior to randomization and be willing to use an
adequate method of contraception (e.g. abstinence, intrauterine device, diaphragm with
spermicide, etc.) for the course of the study through 120 days after the last dose of
study treatment and up to 180 days after last dose of cisplatin
- Male participants of childbearing potential must agree to use an adequate method of
contraception (e.g. abstinence, vasectomy, male condom, etc.) starting with the first
dose of study treatment through 120 days after the last dose of study treatment and up
to 180 days after last dose of cisplatin, and refrain from donating sperm during this
period
- Has adequate organ function
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- Has locally advanced esophageal carcinoma that is resectable or potentially curable
with radiation therapy (as determined by local investigator)
- Has had previous therapy for advanced/metastatic adenocarcinoma or squamous cell
cancer of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the
EGJ
- Has had major surgery, open biopsy, or significant traumatic injury within 28 days
prior to randomization, or anticipation of the need for major surgery during the
course of study treatment
- Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include early-stage cancers (carcinoma in situ or Stage 1) treated with
curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the
skin, in situ cervical cancer, in situ breast cancer that has undergone potentially
curative therapy, and in situ or intramucosal pharyngeal cancer
- Has known active central nervous system metastases and/or carcinomatous meningitis.
- Has an active autoimmune disease that has required systemic treatment in past 2 years
- 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 to the first dose of study treatment, or
has a history of organ transplant, including allogeneic stem cell transplant
- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis, or has an active infection requiring systemic therapy
- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of study medication and up to 180 days after last dose of
cisplatin
- Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1),
anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory
T-cell receptor or has previously participated in a pembrolizumab (MK-3475) clinical
trial
- Has severe hypersensitivity (= Grade 3) to any study treatment (pembrolizumab,
cisplatin, or 5-FU) and/or any of its excipients
- Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis) or human
immunodeficiency virus (HIV) infection
- Has known history of or is positive for hepatitis B or hepatitis C
- Has received a live vaccine within 30 days prior to the first dose of study treatment
- Has had radiotherapy within 14 days of randomization. Participants who received
radiotherapy >14 days prior to randomization must have completely recovered from any
radiotherapy-related AEs/toxicities
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
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Query!
Query!
Query!
Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
25/07/2017
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
10/07/2023
Query!
Sample size
Target
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Accrual to date
Query!
Final
749
Query!
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Query!
Recruitment hospital [1]
0
0
Blacktown Hospital ( Site 2000) - Blacktown
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Recruitment hospital [2]
0
0
Liverpool Hospital. ( Site 2001) - Liverpool
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Recruitment hospital [3]
0
0
Princess Alexandra Hospital ( Site 2005) - Woolloongabba
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Recruitment hospital [4]
0
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Eastern Health ( Site 2002) - Box Hill
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Recruitment hospital [5]
0
0
Peter MacCallum Cancer Centre ( Site 2003) - Melbourne
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Recruitment postcode(s) [1]
0
0
2148 - Blacktown
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Recruitment postcode(s) [2]
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0
2170 - Liverpool
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Recruitment postcode(s) [3]
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0
4102 - Woolloongabba
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Recruitment postcode(s) [4]
0
0
3128 - Box Hill
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Recruitment postcode(s) [5]
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3000 - Melbourne
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Recruitment outside Australia
Country [1]
0
0
United States of America
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California
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United States of America
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Illinois
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Kansas
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Maryland
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United States of America
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Massachusetts
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Michigan
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Missouri
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Tennessee
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Argentina
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Rio Negro
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Argentina
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Buenos Aires
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Argentina
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Cordoba
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Brazil
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Minas Gerais
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Brazil
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Pernambuco
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Brazil
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Rio Grande Do Sul
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Brazil
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RJ
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Brazil
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RS
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Brazil
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Sao Paulo
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Brazil
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SP
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Brazil
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Porto Alegre
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Alberta
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Canada
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Manitoba
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Canada
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Ontario
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Canada
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Quebec
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Chile
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Concepcion
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Chile
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Santiago
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Chile
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Temuco
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China
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Anhui
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China
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Beijing
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China
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Fujian
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China
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Guangdong
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China
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Heilongjiang
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China
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Hubei
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China
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Hunan
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China
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Jiangsu
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China
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Jilin
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China
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Shannxi
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China
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Zhejiang
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China
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Fuzhou
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China
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Shanghai
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China
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Zhengzhou
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Colombia
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Antioquia
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Colombia
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Cordoba
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Costa Rica
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San Jose
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Denmark
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Copenhagen
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Denmark
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Odense
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France
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State/province [49]
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Cedex 8
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France
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Brest
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France
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Caen
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France
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Lille
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France
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Montpellier
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France
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Nantes Cedex 1
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France
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Paris
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France
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Saint Etienne
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0
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Germany
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Dresden
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Germany
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Hamburg
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Germany
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Leipzig
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Germany
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Ludwigsburg
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Germany
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Mannheim
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Germany
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Moenchengladbach
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Germany
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State/province [63]
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Munchen
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Guatemala
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Guatemala
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Guatemala
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State/province [65]
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Quetzaltenango
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0
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Hong Kong
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State/province [66]
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Hong Kong
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0
0
Japan
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State/province [67]
0
0
Aichi
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Country [68]
0
0
Japan
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State/province [68]
0
0
Chiba
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Country [69]
0
0
Japan
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State/province [69]
0
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Ehime
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Country [70]
0
0
Japan
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State/province [70]
0
0
Hokkaido
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0
0
Japan
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State/province [71]
0
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Hyogo
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0
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Japan
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Ibaraki
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0
0
Japan
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State/province [73]
0
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Kagawa
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0
0
Japan
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State/province [74]
0
0
Kanagawa
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0
0
Japan
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State/province [75]
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Oita
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0
0
Japan
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Osaka
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0
0
Japan
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State/province [77]
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Saitama
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0
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Japan
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State/province [78]
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0
Shizuoka
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Country [79]
0
0
Japan
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State/province [79]
0
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Tokyo
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Country [80]
0
0
Japan
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State/province [80]
0
0
Fukuoka
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0
0
Japan
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State/province [81]
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Gifu
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0
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Japan
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State/province [82]
0
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Kumamoto
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Country [83]
0
0
Japan
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State/province [83]
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Niigata
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Country [84]
0
0
Korea, Republic of
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State/province [84]
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Gyeonggi-do
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Country [85]
0
0
Korea, Republic of
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State/province [85]
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Jeollanam Do
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Korea, Republic of
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State/province [86]
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Seoul
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Country [87]
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Malaysia
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State/province [87]
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Selangor
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Country [88]
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Malaysia
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Kuala Lumpur
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Peru
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Arequipa
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Peru
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State/province [90]
0
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Lima
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Country [91]
0
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Romania
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State/province [91]
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Bihor
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Romania
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Cluj
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Country [93]
0
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Romania
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State/province [93]
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Dolj
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0
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Romania
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State/province [94]
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0
Sector 2
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0
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Romania
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Timis
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Romania
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Bucuresti
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Romania
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State/province [97]
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Constanta
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Russian Federation
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Republic Of Bashkortostan
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Russian Federation
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Vsevolzhsk District
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Russian Federation
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Moscow
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Russian Federation
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Saint-Petersburg
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Russian Federation
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St. Petersburg
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Russian Federation
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Tomsk
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South Africa
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Eastern Cape
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South Africa
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Gauteng
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South Africa
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Kwa-Zulu Natal
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South Africa
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Western Cape
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South Africa
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Alberton
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Spain
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Asturias
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Spain
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Barcelona
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Spain
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Cordoba
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Spain
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Madrid
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Spain
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Malaga
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Taiwan
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Kaohsiung
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Taiwan
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New Taipei
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Taiwan
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Taichung
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Taiwan
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Tainan
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Taiwan
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Taipei
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Taiwan
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Taoyuan
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Thailand
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Bangkok
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Thailand
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Songkla
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Turkey
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Adana
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Turkey
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Ankara
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Turkey
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Istanbul
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Turkey
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Izmir
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Turkey
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Malatya
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United Kingdom
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Mid Lothian
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United Kingdom
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Guildford
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United Kingdom
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State/province [129]
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0
Manchester
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Merck Sharp & Dohme LLC
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Address
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Country
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Ethics approval
Ethics application status
Query!
Summary
Brief summary
The purpose of this trial is to evaluate efficacy and safety of pembrolizumab plus standard
of care (SOC) chemotherapy with cisplatin and 5-fluorouracil (5-FU) versus placebo plus SOC
chemotherapy with cisplatin and 5-FU as first-line treatment in participants with locally
advanced or metastatic esophageal carcinoma.
The overall primary efficacy hypotheses are as follows:
1. In participants with esophageal squamous cell carcinoma (ESCC), participants whose
tumors are programmed cell death-ligand 1 (PD-L1)-positive (defined as combined positive
score [CPS] =10), ESCC participants whose tumors are PD-L1 positive (CPS =10), and in
all participants, overall survival (OS) is superior with pembrolizumab plus SOC
chemotherapy compared with placebo plus SOC chemotherapy.
2. In participants with ESCC, participants whose tumors are PD-L1 positive (CPS =10), and
in all participants, progression-free survival (PFS) according to Response Evaluation
Criteria in Solid Tumors (RECIST) 1.1 as assessed by investigator is superior with
pembrolizumab plus SOC chemotherapy compared with placebo plus SOC chemotherapy.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT03189719
Query!
Trial related presentations / publications
Query!
Public notes
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Contacts
Principal investigator
Name
0
0
Medical Director
Query!
Address
0
0
Merck Sharp & Dohme LLC
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Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
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Contact person for public queries
Name
0
0
Query!
Address
0
0
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Country
0
0
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Phone
0
0
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Fax
0
0
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Email
0
0
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT03189719
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