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Study of Pembrolizumab (MK-3475) vs. Best Supportive Care in Participants With Previously Systemically Treated Advanced Hepatocellular Carcinoma (MK-3475-240/KEYNOTE-240)

This study is currently recruiting participants.
Verified October 2017 by Merck Sharp & Dohme Corp.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02702401
First Posted: March 8, 2016
Last Update Posted: October 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
  Purpose

This is a study of pembrolizumab (MK-3475) in participants with previously systemically treated advanced hepatocellular carcinoma (HCC).

The primary objectives of this study are to determine 1) Progression-Free Survival (PFS) and 2) Overall Survival (OS) of pembrolizumab plus best supportive care (BSC) compared with placebo plus BSC. The primary hypotheses of this study are: 1) pembrolizumab plus BSC prolongs PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, assessed by a blinded central imaging vendor compared to placebo plus BSC, and 2) pembrolizumab plus BSC improves OS compared with placebo plus BSC.


Condition Intervention Phase
Hepatocellular Carcinoma Biological: Pembrolizumab Drug: Placebo Other: Best Supportive Care Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III Study of Pembrolizumab (MK-3475) vs. Best Supportive Care as Second-Line Therapy in Subjects With Previously Systemically Treated Advanced Hepatocellular Carcinoma (KEYNOTE-240)

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: Up to approximately 2 years ]
  • Overall Survival (OS) [ Time Frame: Up to approximately 2 years ]

Secondary Outcome Measures:
  • Objective Response Rate (ORR) [ Time Frame: Up to approximately 2 years ]
  • Disease Control Rate (DCR) [ Time Frame: Up to approximately 2 years ]
  • Time to Progression (TTP) [ Time Frame: Up to approximately 2 years ]
  • Duration of Response (DOR) [ Time Frame: Up to approximately 2 years ]

Estimated Enrollment: 408
Actual Study Start Date: May 26, 2016
Estimated Study Completion Date: February 1, 2019
Estimated Primary Completion Date: February 1, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pembrolizumab+Best Supportive Care
Participants receive a pembrolizumab 200 mg intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC.
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Other: Best Supportive Care
Best supportive care will include pain management and management of other potential complications including ascites per local standards of care.
Placebo Comparator: Placebo+Best Supportive Care
Participants receive a placebo IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC.
Drug: Placebo
0.90% w/v sodium chloride IV infusion
Other: Best Supportive Care
Best supportive care will include pain management and management of other potential complications including ascites per local standards of care.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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 Class A liver score within 7 days of first dose of study drug.
  • Has a predicted life expectancy >3 months.
  • Has at least one measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as confirmed by the blinded central imaging vendor.
  • Has a performance status of 0 or 1 using the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 7 days of first dose of study drug.
  • Has documented objective radiographic progression during or after treatment with sorafenib or intolerance to sorafenib.
  • Participants with chronic infection by Hepatitis C Virus (HCV) who are treated (successfully or treatment failure) or untreated are allowed on study. In addition, participants with successful HCV treatment are allowed as long as there are >4 weeks between achieving sustained viral response (SVR12) and start of study drug.
  • Has controlled infection by Hepatitis B Virus (HBV).
  • Is willing to use an adequate method of contraception for the course of the study through at least 120 days or longer based on local regulation after the last dose of study drug (male and female participants of childbearing potential).
  • Demonstrates adequate organ function.

Exclusion Criteria:

  • Is currently participating, or has participated in a study of an investigational agent and received study drug, herbal/complementary oral or IV medicine, or used an investigational device within 4 weeks of the first dose of study drug. Participants must also have recovered from associated therapy (i.e., to Grade ≤1 or baseline) and from adverse events (AEs) due to any prior therapy.
  • Has received sorafenib within 14 days of first dose of study drug.
  • Has had esophageal or gastric variceal bleeding within the last 6 months.
  • Has clinically apparent ascites on physical examination. Note: ascites detectable on imaging studies only ARE allowed.
  • Portal vein invasion at the main portal (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, prior to the start of study drug.
  • Has a known severe hypersensitivity (> Grade 3) to pembrolizumab, its active substance and/or any of its excipients.
  • Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs.
  • 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 drug.
  • Has received locoregional therapy to liver (transcatheter chemoembolization [TACE], transcatheter embolization [TAE], hepatic arterial infusion [HAI], radiation, radioembolization, or ablation) within 4 weeks prior to the first dose of study drug.
  • Has had major surgery to liver or other site within 4 weeks prior to the first dose of study drug.
  • Has had minor surgery (i.e., simple excision, tooth extraction) <7 days prior to the first dose of study drug (Cycle 1, Day 1).
  • Has not recovered adequately (i.e., Grade ≤1 or baseline) from the toxicity and/or complications from any intervention prior to starting study drug.
  • Has a diagnosed additional malignancy within 3 years prior to first dose of study drug 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 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.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the first dose of study drug through 120 days or longer based on local regulation after the last dose of study drug.
  • Has received prior immunotherapy including anti-programmed cell death-1 (anti-PD-1), anti-PD-ligand-1 (anti-PD-L1), or anti-PD-L2 agents, or if the participant has previously participated in Merck pembrolizumab (MK-3475) studies.
  • Has a known history of human immunodeficiency virus (HIV).
  • Has dual active HBV infection and HCV infection at study entry.
  • Has received a live vaccine within 30 days of planned start of study drug (Cycle 1, Day 1).
  Contacts and Locations
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): NCT02702401


Contacts
Contact: Toll Free Number 1-888-577-8839

  Show 57 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02702401     History of Changes
Other Study ID Numbers: 3475-240
2015-004567-36 ( EudraCT Number )
163456 ( Registry Identifier: JAPIC-CTI )
First Submitted: March 3, 2016
First Posted: March 8, 2016
Last Update Posted: October 12, 2017
Last Verified: October 2017

Keywords provided by Merck Sharp & Dohme Corp.:
PD1
PD-1
PDL1
PD-L1

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