Barrett's EsophagusPhase 2NCT01298999
Trial of a Gastrin Receptor Antagonist in Barrett's Esophagus
A Phase 2 study testing YF476 in people with Barrett's Esophagus, run by Columbia University at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Barrett's Esophagus
- What is being tested?
- YF476
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Jun 2010to Dec 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
New York Presbyterian Hospital - Columbia
New York, New York, 10032
About this study
Official title: Randomized Placebo-Controlled Trial of YF476, a Gastrin Receptor Antagonist, in Barrett's Esophagus
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.
Read the 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.
- Conditions
- Barrett's Esophagus
- Being tested
- YF476, Placebo
- Keywords
- Barrett's Esophagus, Esophageal Adenocarcinoma, GERD, Acid Reflux
- Medical subject headings
- Barrett Esophagus, Adenocarcinoma Of Esophagus, Gastroesophageal Reflux
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
YF476Drug
Also called Netazepide
25 mg: one capsule to be taken by mouth once daily for 12 weeks.
PlaceboDrug
Also called Placebo Tablet
Matching placebo: one capsule to be taken by mouth once daily for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| YF476 | Experimental | YF476 (gastrin-receptor antagonist) Receives: Drug: YF476 |
| Placebo | Placebo comparator | Placebo pill (identical in appearance to YF476 pills) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Ki67 Expression
The study is designed to examine change in tissue Ki67 expression, a marker of cellular proliferation.
Measured: 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.
Measured: Up to 3 months from baseline
Secondary outcomes (1)
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.
Measured: Up to 4 months from baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2011 (estimated)
- Study startJun 2010
- Primary completionDec 2017
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Barrett's EsophagusStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Trio Medicines Ltd.
- Responsible party
- Sponsor
- Investigators
- Julian A Abrams, MD, MS, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01298999
- Sponsor's protocol ID
- AAAE9648
- Other IDs
- YFBE-001
- Status last verified
- Nov 2021
- First submitted
- 14 Feb 2011
- Last updated
- 23 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 33782049
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Placebo-Controlled Trial of YF476, a Gastrin Receptor Antagonist, in Barrett's Esophagus
- ClinicalTrials.gov ID
- NCT01298999
- Acronym / sponsor ID
- AAAE9648
- Conditions
- Barrett's Esophagus
- Keywords
- Barrett's Esophagus, Esophageal Adenocarcinoma, GERD, Acid Reflux
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- Trio Medicines Ltd.
- Study start
- Jun 2010
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 18 Feb 2011 (estimated)
- Results
- Posted 23 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| YF476 | Experimental | Drug: YF476YF476 (gastrin-receptor antagonist) |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo pill (identical in appearance to YF476 pills) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| YF476Also: Netazepide25 mg: one capsule to be taken by mouth once daily for 12 weeks. | Drug | YF476 |
| PlaceboAlso: Placebo TabletMatching placebo: one capsule to be taken by mouth once daily for 12 weeks. | Drug | Placebo |
Primary outcome
Mean Ki67 Expression
Time frame: Up to 3 months from baseline
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
Time frame: Up to 3 months from baseline
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.
1 secondary outcome
Number of Participants That Experienced Adverse Events
Time frame: Up to 4 months from baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 33782049Abrams 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.
- Individual participant dataSharing planned: No
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"Less-is-more in Barrett-surveillance" Care Evaluation of Barrett's Patients With Low-Risk in Whom Endoscopic Surveillance is Stopped. The BLISS Project.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julian A Abrams, MD, MS principal investigator
Columbia University
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing YF476 in people with Barrett's Esophagus, run by Columbia University at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Ki67 Expression (time frame: Up to 3 months from baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01298999, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2021.