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Study of Pembrolizumab (MK-3475) or Placebo Given With Best Supportive Care in Asian Participants With Previously Treated Advanced Hepatocellular Carcinoma (MK-3475-394/KEYNOTE-394)

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ClinicalTrials.gov Identifier: NCT03062358
Recruitment Status : Recruiting
First Posted : February 23, 2017
Last Update Posted : September 24, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
The purpose of this study is to determine the efficacy and safety of pembrolizumab or placebo given with best supportive care (BSC) in Asian participants with previously systemically treated advanced hepatocellular carcinoma (HCC). The primary hypothesis of this study is that overall survival is prolonged in participants who receive pembrolizumab compared to those who receive placebo.

Condition or disease Intervention/treatment Phase
Carcinoma, Hepatocellular Biological: pembrolizumab Drug: placebo Other: best supportive care (BSC) Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 330 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III Randomized Double-blind Study of Pembrolizumab Plus Best Supportive Care vs. Placebo Plus Best Supportive Care as Second-Line Therapy in Asian Subjects With Previously Systemically Treated Advanced Hepatocellular Carcinoma (KEYNOTE-394)
Actual Study Start Date : April 27, 2017
Estimated Primary Completion Date : December 23, 2019
Estimated Study Completion Date : April 27, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: pembrolizumab + BSC
Participants receive pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
Biological: pembrolizumab
Administered as an intravenous (IV) infusion every 3 weeks (Q3W)
Other Name: KEYTRUDA®

Other: best supportive care (BSC)
BSC will include pain management and management of other potential complications including ascites per local standards of care.

Placebo Comparator: placebo + BSC
Participants receive placebo by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
Drug: placebo
Normal saline solution administered as an IV infusion Q3W

Other: best supportive care (BSC)
BSC will include pain management and management of other potential complications including ascites per local standards of care.




Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to 2 years ]
    OS is the time from randomization to death due to any cause.


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Up to approximately 2 years ]
    PFS is the time from randomization to first documented disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR).

  2. Objective Response Rate (ORR) [ Time Frame: Up to approximately 2 years ]
    ORR is the proportion of the participants who achieve complete response (CR) or partial response (PR) per RECIST 1.1 by BICR.

  3. Duration Of Response (DOR) [ Time Frame: Up to approximately 2 years ]
    DOR is the time from first documented evidence of CR or PR per RECIST 1.1 by BICR until disease progression per RECIST 1.1 by BICR or death.

  4. Disease Control Rate (DCR) [ Time Frame: Up to approximately 2 years ]
    DCR is the percentage of participants who achieve CR, PR, or stable disease (SD) for ≥6 weeks prior to evidence of disease progression per RECIST 1.1 by BICR.

  5. Time To Progression (TTP) [ Time Frame: Up to approximately 2 years ]
    TTP is the time from randomization to first documented disease progression per RECIST 1.1 by BICR.

  6. Incidence of Adverse Events (AEs) [ Time Frame: From time of signing the informed consent form (ICF) until the end of follow-up (up to approximately 118 Weeks) ]
    Number of participants experiencing any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy

  7. Incidence of Discontinuations [ Time Frame: From time of signing the ICF until the end of study medication (up to approximately 105 Weeks) ]
    Number of participants discontinuing study drug due to an AE



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:

  • Has a HCC diagnosis confirmed by radiology, histology, or cytology (fibrolamellar, and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible)
  • Has Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy and not amenable to a curative treatment approach
  • Has a Child-Pugh A liver score within 7 days prior to first dose of study medication
  • Has a life expectancy of >3 months
  • Has at least one measurable lesion based on RECIST version 1.1 as determined by investigator
  • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 7 days prior to receiving the first dose of study medication
  • Has documented objective radiographic progression during or after treatment with sorafenib or oxaliplatin-based chemotherapy, or else intolerance to sorafenib or oxaliplatin-based chemotherapy
  • Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study therapy
  • Female and male participants of reproductive potential must agree to use adequate contraception starting from the first dose of study medication, throughout the study period, and for up to 120 days after the last dose of study medication

Exclusion Criteria:

  • Is currently participating or has participated in a study with an investigational agent or using an investigational device within 4 weeks of the first dose of study medication
  • Has received sorafenib or oxaliplatin-based chemotherapy within 14 days of first dose of study medication
  • Has had esophageal or gastric variceal bleeding within the last 6 months
  • Has clinically apparent ascites on physical examination
  • Has portal vein invasion at the main portal branch (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging
  • Has had clinically diagnosed hepatic encephalopathy in the last 6 months
  • Has had a solid organ or hematologic transplant
  • Has had prior systemic therapy for HCC in the advanced (incurable) setting other than sorafenib or oxaliplatin-based chemotherapy, prior to start of study medication
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
  • Has received locoregional therapy to liver (transcatheter chemoembolization [TACE], transcatheter embolization [TAE], hepatic arterial infusion [HAI], radiation, radioembolization, or ablation) or other site within 4 weeks prior to the first dose of study medication
  • Has had major surgery to liver or other site within 4 weeks prior to the first dose of study medication
  • Has had a minor surgery ≤7 days prior to the first dose of study medication
  • Has not recovered adequately (i.e., Grade ≤1 or baseline) from the toxicity and/or complications from any intervention prior to study start
  • Has a diagnosed additional malignancy within 3 years prior to first dose of study medication with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cancers
  • Has a known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Has an active infection requiring systemic therapy
  • Is pregnant or breast feeding or expecting to conceive or father starting from the first dose of study medication, throughout the study period, and for up to 120 days after the last dose of study medication
  • Has received prior immunotherapy with an anti-Programmed Cell Death Receptor 1 (PD-1), Programmed Cell Death Receptor Ligand 1 (anti-PD-L1), or anti-Programmed Cell Death Receptor Ligand 2 (PD-L2) or has previously participated in clinical studies with pembrolizumab
  • Has a known history of human immunodeficiency virus (HIV)
  • Has untreated active Hepatitis B
  • Has Hepatitis C in which participants received therapy for HCV <4 weeks prior to receiving pembrolizumab
  • Has received a live vaccine within 30 days prior to the first dose of study therapy

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): NCT03062358


Contacts
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

  Show 40 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03062358     History of Changes
Other Study ID Numbers: 3475-394
MK-3475-394 ( Other Identifier: Merck Registration Number )
First Posted: February 23, 2017    Key Record Dates
Last Update Posted: September 24, 2018
Last Verified: September 2018

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

Keywords provided by Merck Sharp & Dohme Corp.:
Programmed Cell Death Receptor 1 (PD-1)
Programmed Cell Death Receptor Ligand 1 (PD-L1)
Programmed Cell Death Receptor Ligand 2 (PD-L2)
PD1
PD-1
PDL1
PD-L1
PDL2

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Pembrolizumab
Antineoplastic Agents