Trial of a Gastrin Receptor Antagonist in Barrett's Esophagus

NCT01298999 | Completed Phase 2 Results DMC

• 2 other identifiers: AAAE9648YFBE-001
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 2

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.

Conditions

Barrett's Esophagus

Keywords

Barrett's Esophagus; Esophageal Adenocarcinoma; GERD; Acid Reflux

Outcome Measures

Primary Outcomes (2)

• Mean Ki67 Expression

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

  Up to 3 months from baseline

• Number of Participants That Experienced Change in Any Biomarker Expression

  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.

  Up to 3 months from baseline

Secondary Outcomes (1)

• Number of Participants That Experienced Adverse Events

  Up to 4 months from baseline

Study Arms (2)

YF476

EXPERIMENTAL

YF476 (gastrin-receptor antagonist)

Drug: YF476

Placebo

PLACEBO COMPARATOR

Placebo pill (identical in appearance to YF476 pills)

Drug: Placebo

Interventions

YF476 DRUG

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

Also known as: Netazepide

YF476

Placebo DRUG

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

Also known as: Placebo Tablet

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Columbia University: lead
• Trio Medicines Ltd.: collaborator

Study Sites (2)

New York Presbyterian Hospital - Columbia

New York, New York, 10032, United States

Location

National Institute for Health Research

Cambridge, United Kingdom

Location

Related Publications (1)

• Abrams JA, Del Portillo A, Hills C, Compres G, Friedman RA, Cheng B, Poneros J, Lightdale CJ, De La Rue R, di Pietro M, Fitzgerald RC, Sepulveda A, Wang TC. Randomized Controlled Trial of the Gastrin/CCK2 Receptor Antagonist Netazepide in Patients with Barrett's Esophagus. Cancer Prev Res (Phila). 2021 Jun;14(6):675-682. doi: 10.1158/1940-6207.CAPR-21-0050. Epub 2021 Mar 29.

  PMID: 33782049 RESULT

MeSH Terms

Conditions

Barrett Esophagus; Adenocarcinoma Of Esophagus; Gastroesophageal Reflux

Interventions

YF 476

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Esophageal Motility Disorders; Deglutition Disorders

Limitations and Caveats

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.

Results Point of Contact

• Title: Julian A Abrams, MD
• Organization: Columbia University Medical Center

ja660@cumc.columbia.edu

2123059541

Study Officials

• Julian A Abrams, MD, MS

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2011
• First Posted: February 18, 2011
• Study Start: June 1, 2010
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: November 23, 2021
• Results First Posted: November 23, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); US (1)