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Trial of a Gastrin Receptor Antagonist in Barrett's Esophagus

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by Columbia University
Sponsor:
Collaborators:
Trio Medicines Ltd.
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
Julian A Abrams, MD, Columbia University
ClinicalTrials.gov Identifier:
NCT01298999
First received: February 14, 2011
Last updated: July 25, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Barrett's Esophagus
Drug: YF476
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Randomized Placebo-Controlled Trial of YF476, a Gastrin Receptor Antagonist, in Barrett's Esophagus

Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Change in Ki67 expression [ Time Frame: Up to 3 months from baseline ] [ Designated as safety issue: No ]
    The study is designed to examine decreases in tissue Ki67 expression, a marker of cellular proliferation.


Secondary Outcome Measures:
  • Number of participants that experienced change in any biomarker expression [ Time Frame: Up to 3 months from baseline ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    A measure of safety and tolerability


Estimated Enrollment: 22
Study Start Date: June 2010
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: YF476
YF476 (gastrin-receptor antagonist)
Drug: YF476
25 mg: one capsule to be taken by mouth once daily for 12 weeks.
Other Name: Netazepide
Placebo Comparator: Placebo
Placebo pill (identical in appearance to YF476 pills)
Drug: Placebo
Matching placebo: one capsule to be taken by mouth once daily for 12 weeks.
Other Name: No other name

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01298999

Contacts
Contact: Adriana Rodriguez,CCRP 212-304-5606 ar2059@columbia.edu

Locations
United States, New York
New York Presbyterian Hospital - Columbia Recruiting
New York, New York, United States, 10032
Contact: Adriana Rodriguez,CCRP    212-304-5606    ar2059@columbia.edu   
United Kingdom
National Institute for Health Research Recruiting
Cambridge, United Kingdom
Contact: Rebecca Fitzgerald       rcf29@mrc-cu.cam.ac.uk   
Contact: Rachel de la Rue    01223 348270 ext 58270    rd485@medschl.cam.ac.uk   
Sponsors and Collaborators
Julian A Abrams, MD
Trio Medicines Ltd.
National Institute for Health Research, United Kingdom
Investigators
Principal Investigator: Julian A Abrams, MD, MS Columbia University
  More Information

Responsible Party: Julian A Abrams, MD, Assistant Professor of Medicine, Columbia University
ClinicalTrials.gov Identifier: NCT01298999     History of Changes
Other Study ID Numbers: AAAE9648  YFBE-001 
Study First Received: February 14, 2011
Last Updated: July 25, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Columbia University:
Barrett's Esophagus
Esophageal Adenocarcinoma
GERD
Acid Reflux

Additional relevant MeSH terms:
Barrett Esophagus
Digestive System Abnormalities
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Gastrins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 23, 2016