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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)

NCT04003636

Description:

This is a 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. The primary hypothesis is pembrolizumab plus gemcitabine/cisplatin is superior to placebo plus gemcitabine/cisplatin with respect overall survival (OS).

Related Conditions:
  • Extrahepatic Cholangiocarcinoma
  • Gallbladder Carcinoma
  • Intrahepatic Cholangiocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • 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)
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 3475-966
  • SECONDARY ID: 2019-000944-82
  • SECONDARY ID: MK-3475-966
  • SECONDARY ID: KEYNOTE-966
  • SECONDARY ID: 195007
  • NCT ID: NCT04003636

Conditions

  • Biliary Tract Carcinoma

Interventions

DrugSynonymsArms
PembrolizumabMK-3475Arm A (Pembrolizumab+Gemcitabine+Cisplatin)
GemcitabineGemzarArm A (Pembrolizumab+Gemcitabine+Cisplatin)
CisplatinPlatinol®, Platinol®-AQArm A (Pembrolizumab+Gemcitabine+Cisplatin)
PlaceboArm B (Placebo+Gemcitabine+Cisplatin)

Purpose

This is a 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. The primary hypothesis is pembrolizumab plus gemcitabine/cisplatin is superior to placebo plus gemcitabine/cisplatin with respect overall survival (OS).

Trial Arms

NameTypeDescriptionInterventions
Arm A (Pembrolizumab+Gemcitabine+Cisplatin)ExperimentalPembrolizumab, 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.
  • Pembrolizumab
  • Gemcitabine
  • Cisplatin
Arm B (Placebo+Gemcitabine+Cisplatin)Placebo ComparatorPlacebo 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.
  • Gemcitabine
  • Cisplatin
  • Placebo

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:Up to approximately 43 months
Safety Issue:
Description:Overall survival is defined as the time from randomization to death due to any cause.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR
Time Frame:Up to approximately 43 months
Safety Issue:
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.
Measure:Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR
Time Frame:Up to approximately 43 months
Safety Issue:
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.
Measure:Number of Participants Who Experience One or More Adverse Events (AE)
Time Frame:Up to approximately 43 months
Safety Issue:
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.
Measure:Number of Participants Who Discontinued Study Intervention Due to an Adverse Event
Time Frame:Up to approximately 43 months
Safety Issue:
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.
Measure:Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR)
Time Frame:Up to approximately 43 months
Safety Issue:
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.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • Programmed cell death 1 (PD-1)
  • Pembrolizumab
  • Cholangiocarcinoma
  • Gallbladder cancer
  • Checkpoint inhibitor
  • Immunotherapy
  • Biliary
  • Keytruda
  • Bile Duct Cancer

Last Updated

April 5, 2021