- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02589496
Study of Pembrolizumab in Subjects With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma Who Progressed After First-Line Therapy With Platinum and Fluoropyrimidine: Integration of Molecular Subtypes Through Integrative Genomic Analysis
Phase II Study of Pembrolizumab in Subjects With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma Who Progressed After First-Line Therapy With Platinum and Fluoropyrimidine: Integration of Molecular Subtypes Through Integrative Genomic Analysis
This is a single-arm, single-center, open-label trial of pembrolizumab (MK-3475) in subjects with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma who have progressed after failure of any combination chemotherapy containing a platinum and a fluoropyrimidine agent.
Approximately 60 subjects will be enrollment to evaluate the efficacy and safety of pembrolizumab.
Enrollment will begin with all subjects without regard for PD-L1 expression status. An evaluable specimen for PD-L1 status must be available and confirmed prior to enrollment.
All study subjects will be evaluated every 6 weeks (+/- 7 days) following the date of IP drug adminstration for the first six months and every 12 weeks (+/- 7 days) thereafter until progression of disease is documented with radiologic imaging (computed tomography or magnetic resonance imaging).
In the expansion cohort (cohort B), it was expanded on the original cohort based on response analysis and will be opened separately.
Of the 5 MSI-high patients who were enrolled on to original cohort, all 5 MSI high GC patients (100% response rate) demonstrated dramatic response rate.
Based on this finding, in order to proven Pembrolizumab's efficacy to specific MSI-H GC population, we would like enroll 20 more patients in cohort B. Based on our screening protocol, the prevalence of MSI-high in GC is about 15 %. Only MSI-high GC patients will be included. All the eligibility will be the same.
Study Overview
Status
Intervention / Treatment
Detailed Description
Each subject will participate in the trial from the time the subject signs the Informed Consent Form (ICF) through the final contact. After a screening phase of up to 28 days, eligible subjects will receive treatment beginning on Day 1 of each 3-week dosing cycle for pembrolizumab.
Treatment with pembrolizumab or paclitaxel will continue until documented disease progression, unacceptable adverse event(s), undercurrent illness that prevents further administration of treatment, Investigator's decision to withdraw the subject, subject withdraw consent, pregnancy of the subject, noncompliance with trial treatment o procedure requirements, subject receives 24 months of pembrolizumab, or administrative reasons requiring cessation of treatment. After the end of treatment, each subject will be followed for 30 days for adverse event monitoring (serious adverse events and events of clinical interest will be collected for 90 days after the end of treatment or 30 days after the end of treatment if the subject initiates new anticancer therapy, whichever is earlier).
Subjects within the pembrolizumab arm who discontinue after 24 months of therapy for reasons other than disease progression or intolerability or who discontinue after attaining a CR may be eligible for up to one year of retreatment after they have experienced radiographic disease progression.
Subjects who discontinue for reasons other than disease progression will have post-treatment follow-up for disease status until disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up.
All subjects will be followed by telephone for overall survival until death, withdrawal of consent, or the end of the study.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Korea
-
Seoul, Korea, Korea, Republic of, 135-720
- Samsung Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Be willing and able to provide written informed consent/assent for the trial. The subject may also provide consent for Biomedical Research. However, the subject may participate in the main trial without participating in Biomedical Research.
- Be 19 years of age on day of signing informed consent
- Have histologically or cytologically-confirmed diagnosis of gastric or Gastroesophageal Junction Adenocarcinoma
- Have metastatic disease or locally advanced, unresectable disease.
- Has experienced documented objective radiographic or clinical disease progression during or after first-line therapy containing any platinum,fluoropyrimidine doublet.
- Have measurable disease based on RECIST as determined by investigator. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- Be willing to provide fresh tissue for biomarker analysis, and, based on the adequacy of the tissue sample quality for assessment of biomarker status. Repeat samples may be required if adequate tissue is not provided. Newly obtained endoscopic biopsy specimens are preferred to archived samples and formalin-fixed, paraffin-embedded block specimens are preferred to slides.
- Have a performance status of 0 or 1 on the ECOG Performance Scale.
- Demonstrate adequate organ function, all screening labs should be performed within 10 days of treatment initiation.
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
- (Only Cohort B) confirmed as MSI-H via the PCR or IHC staining by institutional standard.
Exclusion Criteria:
- 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 squamous cell or undifferentiated gastric cancer.
- 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 a known history of active Bacillus Tuberculosis
- Hypersensitivity to pembrolizumab or any of its excipients.
- Has had a prior anti-cancer monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered from adverse events due to a previously administered agent.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Has known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
- Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
- Has known history of, or any evidence of active, non-infectious pneumonitis.
- Has an active infection requiring systemic 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 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 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 pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Has a known history of Human Immunodeficiency Virus
- Has known active Hepatitis B or Hepatitis C
- Has received a live vaccine within 30 days of planned start of study therapy.
- Is or has an immediate family member who is investigational site or 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: pembrolizumab
Cohort A :gastric cancer patients Cohort B : MSI-H gastric cancer patients All Chort receive the following treatment.
|
200 mg every 3 weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
RR
Time Frame: up to 2 years
|
Objective: To evaluate RR per mRECIST in advanced gastric or GEJ adenocarcinoma who have progressed on one previous line of therapy, when treated with pembrolizumab Hypothesis: Pembrolizumab increases RR per mRECIST with advanced gastric or GEJ adenocarcinoma who have progressed on 1 previous line of therapy
|
up to 2 years
|
Response Rate
Time Frame: 2 years
|
response rate per RECIST 1.1
|
2 years
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Head and Neck Neoplasms
- Esophageal Diseases
- Adenocarcinoma
- Esophageal Neoplasms
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Pembrolizumab
Other Study ID Numbers
- 2015-09-053
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Sharing Supporting Information Type
- CSR
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Gastric Adenocarcinoma
-
Memorial Sloan Kettering Cancer CenterRecruitingMetastatic Gastric Adenocarcinoma | Metastatic Gastroesophageal Junction Adenocarcinoma | Unresectable Gastric Adenocarcinoma | Unresectable Gastroesophageal Junction Adenocarcinoma | Metastatic Gastric Cancer | Unresectable Esophageal Cancer | Metastatic Esophageal Carcinoma | Metastatic Gastric... and other conditionsUnited States
-
City of Hope Medical CenterActive, not recruitingAdenocarcinoma of the Gastroesophageal Junction | Stage IV Gastric Cancer | Recurrent Gastric Cancer | Diffuse Adenocarcinoma of the Stomach | Intestinal Adenocarcinoma of the Stomach | Mixed Adenocarcinoma of the Stomach | Stage IIIA Gastric Cancer | Stage IIIB Gastric Cancer | Stage IIIC Gastric Cancer and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Gastric Carcinoma | Adenocarcinoma of the Gastroesophageal Junction | Diffuse Gastric Adenocarcinoma | Gastric Intestinal Type Adenocarcinoma | Gastric Mixed AdenocarcinomaUnited States, Canada
-
University of ChicagoNational Cancer Institute (NCI)RecruitingGastric Adenocarcinoma | Esophageal Adenocarcinoma | Stage IIIA Gastric Cancer | Stage IIIB Gastric Cancer | Stage IIIC Gastric Cancer | Stage IIB Gastric Cancer | Stage IIIA Esophageal Adenocarcinoma | Stage IIIB Esophageal Adenocarcinoma | Stage IIIC Esophageal AdenocarcinomaUnited States
-
H. Lee Moffitt Cancer Center and Research InstituteActive, not recruitingGastric Cancer | Gastric Adenocarcinoma | Gastroesophageal Junction AdenocarcinomaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)RecruitingClinical Stage III Gastric Cancer AJCC v8 | Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 | Clinical Stage IV Gastric Cancer AJCC v8 | Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8 | Metastatic Gastric Adenocarcinoma | Metastatic Gastroesophageal Junction... and other conditionsUnited States, Puerto Rico
-
Ukrainian Society of Clinical OncologyRecruitingStomach Cancer | Gastric Cancer | Gastric Adenocarcinoma | Gastrointestinal Cancer | Gastroesophageal Junction Adenocarcinoma | Advanced Gastric Adenocarcinoma | GastroEsophageal Cancer | Stomach Neoplasm | Gastric Neoplasm | Advanced Gastric Carcinoma | Advanced Gastroesophageal Junction AdenocarcinomaUkraine
-
M.D. Anderson Cancer CenterRecruitingClinical Stage III Gastric Cancer AJCC v8 | Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 | Clinical Stage IV Gastric Cancer AJCC v8 | Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8 | Metastatic Gastric Adenocarcinoma | Metastatic Gastroesophageal Junction... and other conditionsUnited States
-
National Cancer Institute (NCI)Not yet recruitingClinical Stage III Gastric Cancer AJCC v8 | Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 | Clinical Stage IV Gastric Cancer AJCC v8 | Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8 | Metastatic Gastric Adenocarcinoma | Metastatic Gastroesophageal Junction... and other conditions
-
National Cancer Institute (NCI)CompletedAdenocarcinoma of the Gastroesophageal Junction | Stage IV Gastric Cancer | Recurrent Gastric Cancer | Diffuse Adenocarcinoma of the Stomach | Intestinal Adenocarcinoma of the Stomach | Mixed Adenocarcinoma of the Stomach | Stage IIIA Gastric Cancer | Stage IIIB Gastric Cancer | Stage IIIC Gastric CancerUnited States
Clinical Trials on pembrolizumab
-
University Medical Center GroningenCompleted
-
Incyte CorporationMerck Sharp & Dohme LLCCompletedMelanomaUnited States, France, Italy, United Kingdom, Spain, Belgium, Israel, Mexico, Japan, Canada, Netherlands, Sweden, Korea, Republic of, Australia, Russian Federation, Chile, Germany, Poland, Ireland, New Zealand, Denmark, Switzerland, South Africa
-
Merck Sharp & Dohme LLCCompletedMelanomaAustralia, South Africa, Spain, Sweden
-
Acerta Pharma BVMerck Sharp & Dohme LLCCompletedMetastatic Urothelial CarcinomaUnited States
-
HUYABIO International, LLC.Active, not recruitingNon Small Cell Lung CancerUnited States
-
Prof. Dr. Matthias PreusserUnknownPrimary Central Nervous System LymphomaAustria
-
Yonsei UniversityNot yet recruitingMucosal Melanoma | Acral MelanomaKorea, Republic of
-
Academisch Medisch Centrum - Universiteit van Amsterdam...Merck Sharp & Dohme LLC; PTC TherapeuticsRecruitingColorectal Cancer | Endometrium CancerNetherlands
-
Michael BoyiadzisMerck Sharp & Dohme LLCCompletedAcute Myeloid LeukemiaUnited States