Trial of a Gastrin Receptor Antagonist in Barrett's Esophagus
November 22, 2021 updated by: Columbia University
Randomized Placebo-Controlled Trial of YF476, a Gastrin Receptor Antagonist, in Barrett's Esophagus
The purpose of this study is to determine whether treatment with an experimental drug called YF476 in patients with Barrett's esophagus reduces the expression of tissue markers that are associated with an increased risk of developing esophageal cancer.
Study Overview
Detailed Description
The association between gastro-esophageal reflux disease (GERD) and cancer of the esophagus is well-established.
Barrett's esophagus (BE) is a condition in which the lining of the part of the esophagus changes to look like small intestine, and this change occurs in the setting of GERD.
Patients with BE are at increased risk for developing esophageal cancer.
It is recommended that all patients with BE take medicines called proton pump inhibitors (PPIs), which greatly reduce the acid produced by the stomach, in the hopes of reducing the risk of esophageal cancer.
However, by reducing the acid level in the stomach, levels of a hormone called gastrin are increased.
There is laboratory data to suggest that gastrin may have effects that actually promote the development of cancer, including esophageal cancer.
The investigators previously showed that BE patients with very high gastrin levels are more likely to have either advanced precancerous changes (also called high grade dysplasia) or cancer of the esophagus.
As such, the obvious question is raised: does gastrin promote the development of cancer in BE? YF476 is a new drug that blocks the effects of gastrin.
Trials in healthy subjects have demonstrated that the drug is safe and well-tolerated.
The investigators therefore propose to conduct a randomized placebo-controlled trial of YF476 in patients with Barrett's esophagus.
The primary hypothesis is that treatment with YF476 will reduce the expression of tissue markers that are associated with an increased risk of developing esophageal cancer.
Study Type
Interventional
Enrollment (Actual)
27
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Cambridge, United Kingdom
- National Institute for Health Research
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New York
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New York, New York, United States, 10032
- New York Presbyterian Hospital - Columbia
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Age >= 18 years, with histologically confirmed diagnosis of Barrett's Esophagus without dysplasia
- Minimum of 1 cm circumferential Barrett's mucosa on endoscopy or at least 2 cm maximal contiguous extent of Barrett's mucosa
- Proton pump inhibitor use at least once daily for at least twelve months prior to enrolment, and stable dose of PPI for the three months before enrolment
- ECOG performance status ≤ 2 and Karnofsky ≥ 60%
- Normal organ and marrow function
- Use of adequate contraception during the study
- Willingness to comply with all treatment and follow up procedures
- Ability to understand and the willingness to sign a written informed consent document
- Up to date with all age appropriate cancer screening tests, as per American Cancer Society guidelines
Exclusion Criteria:
- Histologically confirmed BE with high grade dysplasia, invasive carcinoma of the esophagus, low grade dysplasia
- Prior endoscopic therapy for BE
- History of esophageal or gastric surgery
- History of atrophic gastritis, pernicious anemia, or Zollinger-Ellison syndrome
- Participation in a trial of an investigational medicinal product within the previous 28 days
- Prolonged QTc interval >450 msec
- History of allergic reactions attributed to compounds of similar chemical composition to YF476
- History of baseline findings of: diabetes mellitus requiring insulin therapy; pancreatitis; hepatitis B, hepatitis C or HIV; malabsorption syndrome or inability to swallow or retain oral medicine; major surgery ≤ 28 days prior to enrollment; ECOG performance status ≥ 2; or another cancer within 3 years except for basal carcinoma of the skin or cervical carcinoma in situ; any clinically significant and uncontrolled major morbidity
- Certain medicines and herbal remedies taken during the 7 days before the start of study drug
- Has evidence of cancer at the time of enrolment, or has surveillance tests planned within 21 weeks after enrollment
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: YF476
YF476 (gastrin-receptor antagonist)
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25 mg: one capsule to be taken by mouth once daily for 12 weeks.
Other Names:
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Placebo Comparator: Placebo
Placebo pill (identical in appearance to YF476 pills)
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Matching placebo: one capsule to be taken by mouth once daily for 12 weeks.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Mean Ki67 Expression
Time Frame: Up to 3 months from baseline
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The study is designed to examine change in tissue Ki67 expression, a marker of cellular proliferation.
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Up to 3 months from baseline
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Number of Participants That Experienced Change in Any Biomarker Expression
Time Frame: Up to 3 months from baseline
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Participants with changes in gene expression were assessed by RNA-sequencing (i.e., sample has sufficient RNA for analysis) between baseline and up to 3 months are tallied.
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Up to 3 months from baseline
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Number of Participants That Experienced Adverse Events
Time Frame: Up to 4 months from baseline
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A measure of safety and tolerability.
Participants with recorded adverse events were tallied.
The events include any adverse events and/or severe adverse events.
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Up to 4 months from baseline
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Julian A Abrams, MD, MS, Columbia University
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2010
Primary Completion (Actual)
December 1, 2017
Study Completion (Actual)
December 1, 2017
Study Registration Dates
First Submitted
February 14, 2011
First Submitted That Met QC Criteria
February 17, 2011
First Posted (Estimate)
February 18, 2011
Study Record Updates
Last Update Posted (Actual)
November 23, 2021
Last Update Submitted That Met QC Criteria
November 22, 2021
Last Verified
November 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- AAAE9648
- YFBE-001 (Other Identifier: Trio)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
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