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Study of Pembrolizumab (MK-3475) Versus Investigator's Choice Standard Therapy for Participants With Advanced Esophageal/Esophagogastric Junction Carcinoma That Progressed After First-Line Therapy (MK-3475-181/KEYNOTE-181)

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ClinicalTrials.gov Identifier: NCT02564263
Recruitment Status : Active, not recruiting
First Posted : September 30, 2015
Last Update Posted : May 8, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE September 29, 2015
First Posted Date  ICMJE September 30, 2015
Last Update Posted Date May 8, 2019
Actual Study Start Date  ICMJE December 1, 2015
Actual Primary Completion Date October 15, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 12, 2017)
Overall Survival (OS) [ Time Frame: Up to 5 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 29, 2015)
  • Progression-free Survival (PFS) [ Time Frame: Up to 3 years ]
  • Overall Survival (OS) [ Time Frame: Up to 3 years ]
Change History Complete list of historical versions of study NCT02564263 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 12, 2017)
  • Objective Response Rate (ORR) [ Time Frame: Up to 5 years ]
  • Progression-free Survival (PFS) [ Time Frame: Up to 5 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 29, 2015)
Overall Response Rate (ORR) [ Time Frame: Up to 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Pembrolizumab (MK-3475) Versus Investigator's Choice Standard Therapy for Participants With Advanced Esophageal/Esophagogastric Junction Carcinoma That Progressed After First-Line Therapy (MK-3475-181/KEYNOTE-181)
Official Title  ICMJE A Phase III Randomized Open-Label Study of Single Agent Pembrolizumab vs Physicians' Choice of Single Agent Docetaxel, Paclitaxel, or Irinotecan in Subjects With Advanced/Metastatic Adenocarcinoma and Squamous Cell Carcinoma of the Esophagus That Have Progressed After First-Line Standard Therapy (KEYNOTE-181)
Brief Summary In this study, participants with advanced or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or Siewert type I adenocarcinoma of the esophagogastric junction (EGJ) that has progressed after first-line standard therapy will be randomized to receive either single agent pembrolizumab or the Investigator's choice of standard therapy with paclitaxel, docetaxel, or irinotecan. The primary study hypothesis is that treatment with pembrolizumab will prolong overall survival (OS) as compared to treatment with standard therapy.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Esophageal Carcinoma
  • Esophagogastric Junction Carcinoma
Intervention  ICMJE
  • Biological: pembrolizumab
    IV Q3W
    Other Names:
    • KEYTRUDA®
    • MK-3475
  • Drug: paclitaxel
    IV on Days 1, 8, and 15 of every 28-day (4-week) cycle
  • Drug: docetaxel
    IV on Day 1 of every 21-day (3-week) cycle
  • Drug: irinotecan
    IV on Day 1 of every 14-day (2-week) cycle
Study Arms  ICMJE
  • Experimental: Pembrolizumab
    Participants receive pembrolizumab 200 mg, intravenously (IV) on Day 1 of every 21-day (3-week) cycle (Q3W) for up to 35 administrations (approximately 2 years)
    Intervention: Biological: pembrolizumab
  • Active Comparator: Standard Therapy
    Participants receive Investigator's choice of paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle
    Interventions:
    • Drug: paclitaxel
    • Drug: docetaxel
    • Drug: irinotecan
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 12, 2019)
628
Original Estimated Enrollment  ICMJE
 (submitted: September 29, 2015)
600
Estimated Study Completion Date  ICMJE December 31, 2020
Actual Primary Completion Date October 15, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically- or cytologically-confirmed diagnosis of adenocarcinoma or squamous cell carcinoma of the esophagus or Siewert type I adenocarcinoma of the EGJ
  • Metastatic disease or locally advanced, unresectable disease
  • Life expectancy of greater than 3 months
  • Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
  • Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
  • Documented radiographic or clinical disease progression on no more or less than one previous line of standard therapy
  • Can provide either a newly obtained or archival tumor tissue sample for intra-tumoral immune-related testing and for anti-programmed cell death (PD)-1
  • Participants of reproductive potential must be willing to use adequate contraception for the course of the study through 120 days after the last dose of pembrolizumab or through 180 days after the last dose of paclitaxel, docetaxel or irinotecan
  • Adequate organ function

Exclusion Criteria:

  • Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study medication
  • Active autoimmune disease that has required systemic treatment in past 2 years
  • Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
  • Known central nervous system (CNS) metastases and/or carcinomatous meningitis (includes past history or current metastasis)
  • Has received prior anti-cancer monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not recovered from adverse events due to a previously administered agent
  • Has had a severe hypersensitivity reaction to treatment with another mAb
  • Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1), or anti-PD-L2 agent, or previously participated in Merck pembrolizumab (MK-3475) study
  • Has a known additional malignancy that has progressed or required active treatment within the last 5 years with the exception of curatively treated basal cell and squamous cell carcinoma of the skin and/or curatively resected in-situ cervical and/or breast cancers, and in-situ or intra-mucosal pharyngeal cancer
  • Received a live vaccine within 30 days of the first dose of study medication
  • Known history of Human Immunodeficiency Virus (HIV) infection
  • Known history of or is positive for hepatitis B (hepatitis B surface antigen reactive) or known active hepatitis C (hepatitis C virus RNA or hepatitis C antibody is detected)
  • History of non-infectious pneumonitis that required steroids or current pneumonitis
  • Active infection requiring systemic therapy
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
  • Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study starting with the screening visit through 120 days after the last dose of pembrolizumab or through 180 days after the last dose of paclitaxel, docetaxel or irinotecan
  • Known allergy, hypersensitivity, or contraindication to paclitaxel, docetaxel, or irinotecan or any components used in their preparation
  • Experienced weight loss >10% over approximately 2 months prior to first dose of study therapy
  • Has ascites or pleural effusion by physical exam
  • Has experienced documented objective radiographic or clinical disease progression during or after receiving more than 1 line of therapy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Argentina,   Australia,   Brazil,   Canada,   China,   Colombia,   Czech Republic,   Czechia,   Denmark,   Estonia,   Finland,   France,   Germany,   Hong Kong,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Malaysia,   Mexico,   Netherlands,   Norway,   Peru,   Portugal,   Russian Federation,   Singapore,   Spain,   Sweden,   Taiwan,   Thailand,   Turkey,   United Kingdom,   United States
 
Administrative Information
NCT Number  ICMJE NCT02564263
Other Study ID Numbers  ICMJE 3475-181
2015-002782-32 ( EudraCT Number )
163145 ( Registry Identifier: JAPAN-CTI )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP