Esophageal Carcinoma MedDRA version: 18.1 Level: PT Classification code 10030155 Term: Oesophageal carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must: - Be > or = to 18 years of age on the day of signing the informed consent. - Have histologically or cytologically confirmed diagnosis of adenocarcinoma or squamous cell carcinoma of the esophagus or Siewert type I adenocarcinoma of the EGJ. - Have metastatic disease or locally advanced, unresectable disease. - Have a life expectancy greater than 3 months. - Have measurable disease based on RECIST 1.1 as determined by the local site investigator/radiology assessment. - Have an ECOG performance status of 0 or 1. - Have experienced documented objective radiographic or clinical disease progression during or after first-line locally or globally recommended therapy. - Provide a tissue sample for intratumoral immune-related GEP analysis. - Demonstrate adequate organ function. - Negative pregnancy test for females of child bearing potential prior to starting study and male and female subjects of childbearing potential must be willing to use an adequate method of contraception. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 300
Exclusion criteria
Exclusion criteria: The subject will be excluded from participating in the trial if the subject: - Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of treatment. - Has an active autoimmune disease that has required systemic treatment in past 2 years. - 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 trial treatment. - Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. - Has had prior anti-cancer monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., < or = to Grade 1 or at baseline) from adverse events due to a previously administered agent. - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or if the subject has previously participated in Merck pembrolizumab (MK-3475) clinical trials. - Has a diagnosed additional malignancy within 5 years prior to treatment allocation with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cervical and/or breast cancers. - Has received a live vaccine within 30 days of planned start of study therapy. - Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subjects participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. - Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). - Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). - Has known history of, or any evidence of interstitial lung disease or active, non-infectious 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 trial. - Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment. - Known allergy or hypersensitivity to paclitaxel, docetaxel, or irinotecan, or any components used in the paclitaxel/docetaxel/irinotecan preparation or other contraindication for taxane therapy. - Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective IRB approval (by chair or designee) is given allowing exception to this criterion for a specific subject.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare Progression Free Survival (PFS) and Overall Survival (OS) per RECIST 1.1 assessed by blinded central imaging vendor in all subjects and in Gene Expression Profile (GEP) high subjects.;Secondary Objective: To evaluate safety and tolerability of study drugs in all subjects, as well as PFS, by investigator assessment, and Overall Response Rate (ORR), by blinded central vendor review, per RECIST 1.1 among GEP high subjects and all subjects, when treated with pembrolizumab compared to investigators choice of paclitaxel, docetaxel, or irinotecan.;Primary end point(s): Progression Free Survival (PFS) and Overall survival (OS) per RECIST 1.1 by blinded central imaging vendor.;Timepoint(s) of evaluation of this end point: Interim analysis is planned after enrollment completed (24 months) and approximately 240 PFS events in GEP high subjects or when the target number of OS events is reached. Results will be reviewed by an external data monitoring committee. Final analysis will be when ? 251 OS events have been observed among GEP high subjects. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. PFS-RECIST 1.1 by investigator assessment 2. Overall Response Rate (ORR)-RECIST 1.1 by blinded central imaging vendor review, and RECIST 1.1 by investigator assessment 3. Safety and tolerability Endpoints;Timepoint(s) of evaluation of this end point: These end points will be evaluated at end of study. | — |
Countries
Argentina, Australia, Colombia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Hong Kong, Ireland, Israel, Italy, Japan, Korea, Democratic People's Republic of, Malaysia, Mexico, New Zealand, Peru, Russian Federation, Singapore, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactInvestigación Clínica
Merck Sharp & Dohme de España S.A.
Outcome results
None listed