Clinical Trial: Trial of a Gastrin Receptor Antagonist in Barrett's Esophagus

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief Summary: 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.

Detailed Summary: 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.
Sponsor: Julian A Abrams, MD

Current Primary Outcome: Change in Ki67 expression [ Time Frame: Up to 3 months from baseline ]

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


Original Primary Outcome: Cellular proliferation [ Time Frame: Baseline and 3 months ]

Current Secondary Outcome:

  • Number of participants that experienced change in any biomarker expression [ Time Frame: Up to 3 months from baseline ]
    Biomarkers associated with esophageal adenocarcinoma, in particular, cyclooxygenase-2 (COX-2), p53, cholecystokinin 2 receptor (CCK2R) and doublecortin-like kinase 1 (DCAMKL1)
  • Number of participants that experienced adverse events (any adverse events and/or severe adverse events) [ Time Frame: Up to 4 weeks after completion of study drug ]
    A measure of safety and tolerability


Original Secondary Outcome:

  • Changes in biomarker expression [ Time Frame: Baseline and 3 months ]
  • Adverse events [ Time Frame: Monthly (4 time points) ]
    Number of Participants with Adverse Events (any adverse events and/or severe adverse events) as a Measure of Safety and Tolerability


Information By: Columbia University

Dates:
Date Received: February 14, 2011
Date Started: June 2010
Date Completion: June 2017
Last Updated: July 25, 2016
Last Verified: July 2016