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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) (KEYNOTE-966)

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ClinicalTrials.gov Identifier: NCT04003636
Recruitment Status : Not yet recruiting
First Posted : July 1, 2019
Last Update Posted : July 24, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
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 study has 2 primary hypotheses: 1. Pembrolizumab plus gemcitabine/cisplatin is superior to placebo plus gemcitabine/cisplatin with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by blinded independent central review (BICR) and 2. Pembrolizumab plus gemcitabine/cisplatin is superior to placebo plus gemcitabine/cisplatin with respect to overall survival (OS).

Condition or disease Intervention/treatment Phase
Biliary Tract Carcinoma Drug: Pembrolizumab Drug: Gemcitabine Drug: Cisplatin Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 788 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Estimated Study Start Date : September 30, 2019
Estimated Primary Completion Date : August 31, 2023
Estimated Study Completion Date : August 31, 2023


Arm Intervention/treatment
Experimental: Arm A (Pembrolizumab+Gemcitabine+Cisplatin)
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.
Drug: Pembrolizumab
Pembrolizumab by intravenous (IV) infusion
Other Name: MK-3475

Drug: Gemcitabine
Gemcitabine by IV infusion
Other Name: Gemzar

Drug: Cisplatin
Cisplatin by IV infusion
Other Names:
  • Platinol®
  • Platinol®-AQ

Placebo Comparator: Arm B (Placebo+Gemcitabine+Cisplatin)
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.
Drug: Gemcitabine
Gemcitabine by IV infusion
Other Name: Gemzar

Drug: Cisplatin
Cisplatin by IV infusion
Other Names:
  • Platinol®
  • Platinol®-AQ

Drug: Placebo
Placebo to pembrolizumab




Primary Outcome Measures :
  1. 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 48 months ]
    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. Progressive Disease (PD) is a ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). 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 progression.

  2. Overall Survival (OS) [ Time Frame: Up to 48 months ]
    Overall survival is defined as the time from randomization to death due to any cause.


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR [ Time Frame: Up to 48 months ]
    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 modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

  2. Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR [ Time Frame: Up to 48 months ]
    For participants who demonstrate 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. Complete Response is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response is a ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is a ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). 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 progression.

  3. Number of Participants Who Experience One or More Adverse Events (AE) [ Time Frame: Up to 48 months ]
    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.

  4. Number of Participants Who Discontinued Study Intervention Due to an Adverse Event [ Time Frame: Up to 48 months ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

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

Exclusion Criteria

  1. Has had previous systemic therapy for advanced (metastatic) or unresectable (locally advanced) biliary tract cancer (intra-or extra hepatic cholangiocarcinoma or gallbladder cancer), with the exception of adjuvant therapy which is allowed.
  2. Has ampullary cancer.
  3. Has small cell cancer, neuroendocrine tumors, lymphoma, sarcoma and/or Mucinous cystic neoplasms.
  4. 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 co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
  5. Has a known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis, as assessed by local site investigator.
  6. Has had an allogenic tissue/solid organ transplant.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04003636


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT04003636     History of Changes
Other Study ID Numbers: 3475-966
2019-000944-82 ( EudraCT Number )
MK-3475-966 ( Other Identifier: Merck Protocol Number )
KEYNOTE-966 ( Other Identifier: Study acronym )
First Posted: July 1, 2019    Key Record Dates
Last Update Posted: July 24, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme Corp.:
programmed cell death 1 (PD-1)
Pembrolizumab
cholangiocarcinoma
gall bladder cancer
check point inhibitor
immunotherapy

Additional relevant MeSH terms:
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Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Cisplatin
Pembrolizumab
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological