Pembrolizumab in Treating Patients With Small Bowel Adenocarcinoma That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery
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|ClinicalTrials.gov Identifier: NCT02949219|
Recruitment Status : Active, not recruiting
First Posted : October 31, 2016
Results First Posted : January 10, 2020
Last Update Posted : January 10, 2020
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Small Intestinal Adenocarcinoma Recurrent Small Intestinal Carcinoma Unresectable Small Intestinal Carcinoma||Other: Laboratory Biomarker Analysis Biological: Pembrolizumab||Phase 2|
I. To determine whether pembrolizumab administered to small bowel adenocarcinoma (SBA) patients demonstrates antitumor activity as measured by the confirmed response rate.
I. To assess survival endpoints (overall survival [OS], progression free survival [PFS]), including stratified analysis by tumor site.
II. To assess whether pembrolizumab is safe in SBA patients by assessing adverse events.
I. To determine whether PD-L1 expression, as measured by immunohistochemistry (IHC), or microsatellite instability (MSI) status is associated with the response rate overall.
II. To determine if Bim levels in tumor-reactive CD11ahighPD-1+CD8+ peripheral blood T cells can objectively monitor responses to pembrolizumab and to determine if excessive release of soluble B7-H1 (soluble [s]PD-L1) by the tumor leads to Bim upregulation and treatment resistance in SBA.
III. To determine if other tissue-based factors, such as total mutational burden, correlate with response to pembrolizumab.
Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months until disease progression, and then every 6 months for up to 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||41 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter Phase II Study of Pembrolizumab (MK-3475) in Patients With Advanced Small Bowel Adenocarcinomas|
|Actual Study Start Date :||March 24, 2017|
|Actual Primary Completion Date :||January 31, 2019|
|Estimated Study Completion Date :||June 1, 2022|
Experimental: Treatment (pembrolizumab)
Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- Overall Confirmed Response Rate [ Time Frame: 1 year (up to 18 cycles) ]The response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients.
- Progression Free Survival [ Time Frame: From study entry to the first of either disease progression or death from any cause, assessed up to 2 years ]Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
- Overall Survival [ Time Frame: From study entry to death from any cause, assessed up to 2 years ]Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
- Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Events Regardless of Attribution [ Time Frame: Up to 2 years ]number of participants who experienced at least one grade 3 or higher adverse events regardless of attribution assessed by National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.03
- Biomarker Levels [ Time Frame: Up to 5 years ]Correlated with clinical data (i.e. response, overall survival, progression free survival, adverse events). These correlations will be done using the Chi-square or Fisher?s exact test for categorical data and Kaplan-Meier methods (including the log-rank test) for the survival endpoints. Univariate Cox regression models will also be done to assess for marker effects on survival endpoints. Descriptive statistics and graphical methods will be used to summarize the data as well. All these analyses will be done overall and by MMR/microsatellite instability status.
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): NCT02949219
|United States, Arizona|
|Mayo Clinic Hospital|
|Phoenix, Arizona, United States, 85054|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, District of Columbia|
|MedStar Georgetown University Hospital|
|Washington, District of Columbia, United States, 20007|
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|United States, South Dakota|
|Rapid City Regional Hospital|
|Rapid City, South Dakota, United States, 57701|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Robert McWilliams||Academic and Community Cancer Research United|