YF476 in Barrett's Esophagus

Inclusion Criteria:

* Aged \>18 years, with histologically confirmed diagnosis of Barrett's esophagus (BE) without dysplasia. A prior endoscopy with biopsies read as indefinite for dysplasia is permitted if biopsies from the most recent endoscopy prior to study entry demonstrated BE without dysplasia.
* Minimum of 1 cm circumferential Barrett's mucosa on endoscopy or at least 2 cm maximal contiguous extent of Barrett's mucosa, as measured from the top of the gastric folds to the squamocolumnar junction (Prague criteria C\>1, any M or any C, M\>2).
* Proton pump inhibitor use at least once daily, for at least 12 months prior to enrolment, and stable dose of PPI for the 3 months before enrolment. Any PPI, dose, and frequency allowable.
* ECOG performance status \<2 and Karnofsky \>60%
* Normal organ and marrow function, defined as white blood cells \>3 x 10e9, absolute neutrophil count \>1.5 x 10e9, platelets \>100 x 10e9, creatinine \<1.5 mg/dL, total bilirubin \<1.5 mg/dL, AST \<100 U/L, ALT \<100 U/L.
* Use of adequate contraception during the study, as follows;
* Post-menopausal women must have had their last menstrual period at least 1 year ago.
* Pre-menopausal women, who are sexually-active, must have had a hysterectomy or bilateral oophorectomy; or must use an intrauterine device (IUD), or spermicide with a diaphragm, cap or condom. Streroid contraceptives such as 'the pill' are not allowed unless in combination with one of the aforementioned barrier contraceptive methods.
* Men must use a condom and spermicide.
* 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, (Columbia University only), and no cancer screening tests planned for the next 21 weeks.

Exclusion Criteria:

* Histologically confirmed BE with high-grade dysplasia.
* Histologically confirmed diagnosis of invasive carcinoma of the esophagus.
* Histologically confirmed BE with low-grade dysplasia that has been diagnosed by at least 2 expert gastrointestinal pathologists.
* Prior endoscopic therapy for BE.
* Any history of esophageal or gastric surgery.
* History of atrophic gastritis, pernicious anemia, or Zollinger-Ellison syndrome.
* Participation in a trial of an IMP within the previous 28 days.
* Prolonged QTc interval \>450 msec.
* History of allergic reactions attributed to compounds of similar chemical composition of YF476.
* History of baseline findings of:
* diabetes mellitus requiring insulin therapy
* pancreatitis (baseline amylase and/or lipase \>2.0 x ULN)
* hepatitis B, hepatitis C or HIV
* malabsorption syndrome or inability to swallow or retain oral medicine
* major surgery \<28 days prior to enrolment
* ECOG performance status \>2
* another cancer within 3 years except for basal carcinoma of the skin or cervical carcinoma in-situ
* also, any clinically significant and uncontrolled major morbidity including but not limited to: serious cardiac disease (unstable angina, s/p myocardial infarction \<1 month); respiratory disease (advanced COPD or pulmonary fibrosis); uncontrolled hypertension; active systemic infection; or psychiatric illness/social situations that would limit compliance with study requirements.
* Certain medicines and herbal remedies taken during the 7 days before the start of the study drug.
* A history of cancer \>3 years from the time of enrolment, and the patient is not up to date with surveillance for that cancer (based on the American Cancer Society guidelines, Columbia University only), has evidence of cancer at the time of enrolment, or has surveillance tests planned within 21 weeks after enrolment.