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Trial of a Gastrin Receptor Antagonist in Barrett's Esophagus

Primary Purpose

Barrett's Esophagus

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

YF476

Placebo

About this trial

This is an interventional prevention trial for Barrett's Esophagus focused on measuring Barrett's Esophagus, Esophageal Adenocarcinoma, GERD, Acid Reflux

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

New York Presbyterian Hospital - Columbia
National Institute for Health Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

YF476

Placebo

Arm Description

YF476 (gastrin-receptor antagonist)

Placebo pill (identical in appearance to YF476 pills)

Outcomes

Primary Outcome Measures

Mean Ki67 Expression

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

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.

Secondary Outcome Measures

Number of Participants That Experienced Adverse Events

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

Full Information

NCT ID

NCT01298999

First Posted

February 14, 2011

Last Updated

November 22, 2021

Sponsor

Columbia University

Collaborators

Trio Medicines Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT01298999

Brief Title

Trial of a Gastrin Receptor Antagonist in Barrett's Esophagus

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2021

Overall Recruitment Status

Completed

Study Start Date

June 2010 (undefined)

Primary Completion Date

December 2017 (Actual)

Study Completion Date

December 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Columbia University

Collaborators

Trio Medicines Ltd.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Barrett's Esophagus

Keywords

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

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

27 (Actual)

8. Arms, Groups, and Interventions

Arm Title

YF476

Arm Type

Experimental

Arm Description

YF476 (gastrin-receptor antagonist)

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo pill (identical in appearance to YF476 pills)

Intervention Type

Drug

Intervention Name(s)

YF476

Other Intervention Name(s)

Netazepide

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Placebo Tablet

Intervention Description

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

Primary Outcome Measure Information:

Title

Mean Ki67 Expression

Description

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

Time Frame

Up to 3 months from baseline

Title

Number of Participants That Experienced Change in Any Biomarker Expression

Description

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.

Time Frame

Up to 3 months from baseline

Secondary Outcome Measure Information:

Title

Number of Participants That Experienced Adverse Events

Description

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

Time Frame

Up to 4 months from baseline

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Julian A Abrams, MD, MS

Organizational Affiliation

Columbia University

Official's Role

Principal Investigator

Facility Information:

Facility Name

New York Presbyterian Hospital - Columbia

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

National Institute for Health Research

City

Cambridge

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

33782049

Citation

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.

Results Reference

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Trial of a Gastrin Receptor Antagonist in Barrett's Esophagus

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