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Pembrolizumab (MK-3475) Plus Gemcitabine/Cisplatin Versus Placebo Plus Gemcitabine/Cisplatin for First-Line Advanced and/or Unresectable Biliary Tract Carcinoma (BTC) (MK-3475-966/KEYNOTE-966)-China Extension Study

Primary Purpose

Biliary Tract Carcinoma

Status
Active
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Pembrolizumab
Gemcitabine
Cisplatin
Placebo
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Biliary Tract Carcinoma focused on measuring Programmed cell death 1 (PD-1), Pembrolizumab, Cholangiocarcinoma, Gallbladder cancer, Checkpoint inhibitor, Immunotherapy, Biliary, Keytruda, Bile Duct Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

  • Has histologically confirmed diagnosis of advanced (metastatic) and/or unresectable (locally advanced) biliary tract cancer (intra-or extrahepatic cholangiocarcinoma or gallbladder cancer)
  • Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1), as determined by the site investigator
  • Participants with a history of hepatitis B or hepatitis C can be enrolled if they meet study criteria
  • Is able to provide archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion
  • Has a life expectancy of greater than 3 months
  • Has adequate organ function

Exclusion Criteria

  • Has had previous systemic therapy for advanced (metastatic) or unresectable (locally advanced) biliary tract cancer (intra-or extra hepatic cholangiocarcinoma or gallbladder cancer)
  • Has ampullary cancer
  • Has small cell cancer, neuroendocrine tumors, lymphoma, sarcoma, mixed tumor histology and/or mucinous cystic neoplasms
  • Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti- programmed cell death ligand 1 or 2 (anti-PD-L1, anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
  • Has a known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis, as assessed by local site investigator
  • Has had an allogenic tissue/solid organ transplant

Sites / Locations

  • Anhui Provincial Hospital ( Site 0140)
  • Beijing Cancer Hospital ( Site 0138)
  • Peking Union Medical College Hospital ( Site 0150)
  • First Affiliated Hospital of The Third Military Medical University ( Site 0130)
  • Fujian Provincial Cancer Hospital ( Site 0154)
  • 900 Hospital of the Joint ( Site 0137)
  • Guangdong Provincial People s Hospital ( Site 0161)
  • Harbin Medical University Cancer Hospital ( Site 0133)
  • Hunan Provincial People Hospital ( Site 0142)
  • Hunan Cancer Hospital ( Site 0132)
  • The Third Xiangya Hospital of Central South University ( Site 0157)
  • The 81st Hospital of PLA ( Site 0128)
  • The First Hospital of Jilin University ( Site 0131)
  • Zhongshan Hospital Fudan University ( Site 0129)
  • Renji Hospital Shanghai Jiaotong University School of Medicine ( Site 0158)
  • Fudan University Shanghai Cancer Center ( Site 0160)
  • Tangdu Hospital ( Site 0146)
  • The First Affiliated Hospital of Xi an Jiaotong University ( Site 0145)
  • West China Hospital of Sichuan University ( Site 0147)
  • Tianjin Medical University Cancer Institute & Hospital ( Site 0155)
  • The First Affiliated Hospital Zhejiang University ( Site 0136)
  • Zhejiang Cancer Hospital ( Site 0134)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm A (Pembrolizumab+Gemcitabine+Cisplatin)

Arm B (Placebo+Gemcitabine+Cisplatin)

Arm Description

Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.

Placebo to Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.

Outcomes

Primary Outcome Measures

Overall Survival (OS)
Overall survival is defined as the time from randomization to death due to any cause.

Secondary Outcome Measures

Progression-free Survival (PFS) per RECIST 1.1 as Assessed by BICR
Progression-free survival is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first.
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
ORR is defined as the percentage of participants who have a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: a ≥30% decrease in the sum of diameters [SOD] of target lesions) as assessed by BICR per RECIST 1.1, which is adjusted for this study to allow a maximum of 10 target lesions in total and 5 per organ.
Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR
For participants who demonstrate a confirmed CR or PR, DOR is the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.
Number of Participants Who Experience One or More Adverse Events (AE)
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Full Information

First Posted
June 8, 2021
Last Updated
February 8, 2023
Sponsor
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT04924062
Brief Title
Pembrolizumab (MK-3475) Plus Gemcitabine/Cisplatin Versus Placebo Plus Gemcitabine/Cisplatin for First-Line Advanced and/or Unresectable Biliary Tract Carcinoma (BTC) (MK-3475-966/KEYNOTE-966)-China Extension Study
Official Title
A Phase 3 Randomized, Double Blind Study of Pembrolizumab Plus Gemcitabine/Cisplatin Versus Placebo Plus Gemcitabine/Cisplatin as First-Line Therapy in Participants With Advanced and/or Unresectable Biliary Tract Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 10, 2020 (Actual)
Primary Completion Date
December 15, 2022 (Actual)
Study Completion Date
November 29, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In this China Extension study, pembrolizumab plus gemcitabine/cisplatin will be compared with placebo plus gemcitabine/cisplatin as first-line therapy in Chinese adults with advanced and/or unresectable biliary tract carcinoma. The primary hypothesis is pembrolizumab plus gemcitabine/cisplatin is superior to placebo plus gemcitabine/cisplatin with respect to overall survival (OS).
Detailed Description
The China extension study will include participants previously enrolled in China in the global study for MK-3475-966 (NCT04003636) plus those enrolled during the China extension enrollment period. A total of approximately 158 Chinese participants will be enrolled.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Biliary Tract Carcinoma
Keywords
Programmed cell death 1 (PD-1), Pembrolizumab, Cholangiocarcinoma, Gallbladder cancer, Checkpoint inhibitor, Immunotherapy, Biliary, Keytruda, Bile Duct Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
46 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A (Pembrolizumab+Gemcitabine+Cisplatin)
Arm Type
Experimental
Arm Description
Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.
Arm Title
Arm B (Placebo+Gemcitabine+Cisplatin)
Arm Type
Placebo Comparator
Arm Description
Placebo to Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
MK-3475
Intervention Description
Pembrolizumab by intravenous (IV) infusion
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
Gemzar
Intervention Description
Gemcitabine by IV infusion
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Platinol®, Platinol®-AQ
Intervention Description
Cisplatin by IV infusion
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo to pembrolizumab
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
Overall survival is defined as the time from randomization to death due to any cause.
Time Frame
Up to approximately 38 months
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS) per RECIST 1.1 as Assessed by BICR
Description
Progression-free survival is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first.
Time Frame
Up to approximately 26 months
Title
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Description
ORR is defined as the percentage of participants who have a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: a ≥30% decrease in the sum of diameters [SOD] of target lesions) as assessed by BICR per RECIST 1.1, which is adjusted for this study to allow a maximum of 10 target lesions in total and 5 per organ.
Time Frame
Up to approximately 26 months
Title
Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR
Description
For participants who demonstrate a confirmed CR or PR, DOR is the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.
Time Frame
Up to approximately 38 months
Title
Number of Participants Who Experience One or More Adverse Events (AE)
Description
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time Frame
Up to approximately 38 months
Title
Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)
Description
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time Frame
Up to approximately 38 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Has histologically confirmed diagnosis of advanced (metastatic) and/or unresectable (locally advanced) biliary tract cancer (intra-or extrahepatic cholangiocarcinoma or gallbladder cancer) Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1), as determined by the site investigator Participants with a history of hepatitis B or hepatitis C can be enrolled if they meet study criteria Is able to provide archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion Has a life expectancy of greater than 3 months Has adequate organ function Exclusion Criteria Has had previous systemic therapy for advanced (metastatic) or unresectable (locally advanced) biliary tract cancer (intra-or extra hepatic cholangiocarcinoma or gallbladder cancer) Has ampullary cancer Has small cell cancer, neuroendocrine tumors, lymphoma, sarcoma, mixed tumor histology and/or mucinous cystic neoplasms Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti- programmed cell death ligand 1 or 2 (anti-PD-L1, anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137) Has a known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis, as assessed by local site investigator Has had an allogenic tissue/solid organ transplant
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Anhui Provincial Hospital ( Site 0140)
City
Hefei
State/Province
Anhui
ZIP/Postal Code
230001
Country
China
Facility Name
Beijing Cancer Hospital ( Site 0138)
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100036
Country
China
Facility Name
Peking Union Medical College Hospital ( Site 0150)
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Facility Name
First Affiliated Hospital of The Third Military Medical University ( Site 0130)
City
Chongqing
State/Province
Chongqing
ZIP/Postal Code
400038
Country
China
Facility Name
Fujian Provincial Cancer Hospital ( Site 0154)
City
Fuzhou
State/Province
Fujian
ZIP/Postal Code
350014
Country
China
Facility Name
900 Hospital of the Joint ( Site 0137)
City
Fuzhou
State/Province
Fujian
ZIP/Postal Code
350025
Country
China
Facility Name
Guangdong Provincial People s Hospital ( Site 0161)
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China
Facility Name
Harbin Medical University Cancer Hospital ( Site 0133)
City
Harbin
State/Province
Heilongjiang
ZIP/Postal Code
610000
Country
China
Facility Name
Hunan Provincial People Hospital ( Site 0142)
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410005
Country
China
Facility Name
Hunan Cancer Hospital ( Site 0132)
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410013
Country
China
Facility Name
The Third Xiangya Hospital of Central South University ( Site 0157)
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410013
Country
China
Facility Name
The 81st Hospital of PLA ( Site 0128)
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210031
Country
China
Facility Name
The First Hospital of Jilin University ( Site 0131)
City
Chanchun
State/Province
Jilin
ZIP/Postal Code
130021
Country
China
Facility Name
Zhongshan Hospital Fudan University ( Site 0129)
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Name
Renji Hospital Shanghai Jiaotong University School of Medicine ( Site 0158)
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200127
Country
China
Facility Name
Fudan University Shanghai Cancer Center ( Site 0160)
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
201315
Country
China
Facility Name
Tangdu Hospital ( Site 0146)
City
XI An
State/Province
Shanxi
ZIP/Postal Code
710038
Country
China
Facility Name
The First Affiliated Hospital of Xi an Jiaotong University ( Site 0145)
City
XI An
State/Province
Shanxi
ZIP/Postal Code
710048
Country
China
Facility Name
West China Hospital of Sichuan University ( Site 0147)
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Facility Name
Tianjin Medical University Cancer Institute & Hospital ( Site 0155)
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300060
Country
China
Facility Name
The First Affiliated Hospital Zhejiang University ( Site 0136)
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Facility Name
Zhejiang Cancer Hospital ( Site 0134)
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310022
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Links:
URL
http://merckoncologyclinicaltrials.com
Description
Merck Oncology Clinical Trials Information

Learn more about this trial

Pembrolizumab (MK-3475) Plus Gemcitabine/Cisplatin Versus Placebo Plus Gemcitabine/Cisplatin for First-Line Advanced and/or Unresectable Biliary Tract Carcinoma (BTC) (MK-3475-966/KEYNOTE-966)-China Extension Study

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