Digestive System Diseases

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Esophageal Diseases

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All Drugs and Chemicals

Gastrins

Placebo pill (identical in appearance to YF476 pills)

25 mg: one capsule to be taken by mouth once daily for 12 weeks.

YF476

Matching placebo: one capsule to be taken by mouth once daily for 12 weeks.

Placebo

Julian A Abrams, MD, MS

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.

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.

Trial of a Gastrin Receptor Antagonist in Barrett's Esophagus

Randomized Placebo-Controlled Trial of YF476, a Gastrin Receptor Antagonist, in Barrett's Esophagus

The study is designed to examine change in tissue Ki67 expression, a marker of cellular proliferation.

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.

A measure of safety and tolerability. Participants with recorded adverse events were tallied. The events include any adverse events and/or severe adverse events.

Trio Medicines Ltd.

Columbia University

YF476 (gastrin-receptor antagonist)

YF476: 25 mg: one capsule to be taken by mouth once daily for 12 weeks.

Placebo pill (identical in appearance to YF476 pills)

Placebo: Matching placebo: one capsule to be taken by mouth once daily for 12 weeks.

Total

Age, Continuous

Sex: Female, Male

Race, white

Race/Ethnicity, Customized

Waist circumference

Current smoker

Proton Pump Inhibitor (PPI) frequency

Aspirin Use

Maximal Barrett's esophagus length (Prague M)

Barrett's Esophagus length

Hiatal hernia size

Serum gastrin

Plasma CgA

Relatively small sample size; study enrollment was limited to Barrett's esophagus without dysplasia, limited analysis of treatment related to later stages of disease progression; only one dose was tested which limits possibility that higher doses would have been more bioactive in Barrett's esophagus tissue.

Julian A Abrams, MD

Analysis limited to those who completed study (10 subjects in the intervention group and 10 subjects in the placebo group).

Mean Ki67 Expression

Number of Participants That Experienced Change in Any Biomarker Expression

Serious Adverse Event

Any Adverse Event

Number of Participants That Experienced Adverse Events

Overall Study

Patients will take 25 mg YF476 once daily for 12 weeks

Patients will take matching placebo once daily for 12 weeks

YF476 placebo

Julian A Abrams, MD MS

A phase 2, randomised, double-blind, out-patient trial to determine if YF476 is a safe and effective treatment in patients with Barrett's esophagus.

YF476 in Barrett's Esophagus

Randomized, Placebo-controlled Trial of YF476, a Gastrin Receptor Antagonist, in Barrett's Esophagus

Esophagogastroduodenoscopy (EGD) was performed to enable taking biopsies for assessment of Ki67 expression, a marker of cellular proliferation. Ki67 expression was assessed by immunohistochemistry and calculating the number of Ki67 positive cells per mm\^2 of Barrett's epithelium.

Blood samples were taken for assay of biomarkers associated with esophageal adenocarcinoma. Changes in biomarker expression were derived from RNA-Sequencing and calculated as log-fold change comparing the treatment group to the placebo group. The nature of how results are derived by RNA-sequencing means summary statistics cannot be generated individually for each arm and a value has not been calculated for each individual participant. Therefore, results are reported as the relative change in biomarker expression in the treatment arm compared to the placebo arm.

Blood samples were taken to assess the effects of YF476 on fasting serum gastrin, a marker of gastric acid suppression

Blood samples were taken to assess the effects of YF476 on fasting plasma CgA, a marker of ECL cell hyperplasia

University of Cambridge

Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment

Patients will take 25 mg YF476 once daily for 12 weeks

YF476: gastrin receptor antagonist

Treatment

Patients will take matching placebo once daily for 12 weeks

YF476 placebo: placebo

YF476 Placebo

Age, Categorical

Race (NIH/OMB)

United States

United Kingdom

Region of Enrollment

Ki67 expression

Fasting serum gastrin concentration (marker of gastric acid suppression)

Fasting plasma CgA concentration (marker of ECL cell hyperplasia)

Dr Malcolm Boyce

Baseline

Week 12

3 patients in the treatment arm and 1 patient in the placebo arm were withdrawn from the study due to reasons unrelated to the treatment. Therefore, Week 12 data show results from 10 patients per arm.

Change in Ki67 Biomarker Expression

CCK2R, Week 12

PTGS2, Week 12

DCLK1, Week 12

3 patients in the treatment arm were withdrawn from the study due to reasons unrelated to the treatment. Therefore, results are reported for 10 patients.

Expression of Biomarkers Potentially Associated With Esophageal Adenocarcinoma (EAC)

Week 4

Week 6

Week 8

Follow-up

After 6 patients (3 per treatment) had their Week 4 and 8 visits, the protocol was amended so that those visits were replaced by a single visit at Week 6 in order to reduce the total number of visits.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of a Gastrin Receptor Antagonist in Barrett's Esophagus	NCT01298999	Barrett's Esoph...	YF476 Placebo	18 Years -	Columbia University
Trial of a Gastrin Receptor Antagonist in Barrett's Esophagus	NCT01298999	Barrett's Esoph...	YF476 Placebo	18 Years -	Columbia University
YF476 in Barrett's Esophagus	NCT02597712	Barrett's Esoph...	YF476 YF476 placebo	18 Years -	Trio Medicines Ltd.

Spots Global Cancer Trial Database for acid reflux

Every month we try and update this database with for acid reflux cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for acid reflux

Every month we try and update this database with for acid reflux cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for acid reflux cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.