A Phase III study of Pembrolizumab compared to Physicians’ choice of Docetaxel, Paclitaxel, or Irinotecan in Previously Treated Subjects with Advanced/Metastatic Adenocarcinoma or Squamous Cell Carcinoma of the Esophagus
- Conditions
- Esophageal CarcinomaMedDRA version: 20.0Level: PTClassification code 10030155Term: Oesophageal carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-002782-32-NL
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 720
Subjects must:
- Be = 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.
Subjects with direct invasion into adjacent organs such as the aorta or
trachea (T4b disease) should be closely evaluated for bleeding risk prior
to enrollment and a sponsor consultation before enrollment is required.
- Have a life expectancy greater than 3 months.
- Have measurable disease based on RECIST 1.1 as determined by local
site investigator/radiology assessment.
- Have an ECOG performance status of 0 or 1.
- Have experienced documented radiographic or clinical disease
progression on one previous line of standard therapy. This study will
only include second-line subjects. Second-line subjects are defined as
those who have progressed during or after receiving at least one dose of
standard therapy given in a first line setting.
- Provide either a newly obtained or archival tissue sample for
intratumoral immunerelated GEP analysis and PD-L1 by
immunohistochemistry analysis. Newly-obtained tissue is preferred.
Formalin-fixed, paraffin-embedded (FFPE) block specimens are preferred
to slides.
- 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 360
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 360
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 investigational 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 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. Subjects must have recovered from adverse events due to a previously administered agent to baseline toxicity grade or to grade 1 or less prior to enrollment.
- 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.
- Previously had a severe hypersensitivity reaction to treatment with
another monoclonal antibody (mAb).
- Has experienced documented objective radiographic or clinical disease
progression during or after receiving more than 1 line of therapy.
- Has a known additional malignancy that progressed or required active
treatment within the last 5 years. Exceptions include 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
intramucosal pharyngeal cancer. Has received a live vaccine within 30
days of planned start of pembrolizumab.
- Has a history or current evidence of any condition, therapy, or
laboratory abnormality that might confound the results of the trial,
interfere with the subject's 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)
infection. No HIV testing is required unless mandated by local health
authority.
- Has known history of or is positive for Hepatitis B (hepatitis B surface antigen reactive) or known Hepatitis C (hepatitis C virus RNA or hepatitis C antibody is detected). No hepatitis testing is required unless mandated by local health authority.
- 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 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.
- Has a Known allergy, hypersensitivity, or contraindication to
preselected chemotherapy agent (i.e. 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 clinically apparent ascites or pleural effusion by physical exam.
(Note that small amount of ascites which is only detectable
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method