Tamoxifen to Treat Barrett's Metaplasia

Treat Barrett's esophagus (BE) patients with tamoxifen to determine the effects on Barrett's
metaplasia as measured by changes in Barrett's esophagus appearance by endoscopy and
histology. Tamoxifen treatment may induce SOX2 expression, decrease CDX2 and promote
esophageal stem cell activity, leading to regression of Barrett's metaplasia. To test this
hypothesis, we will conduct a prospective, pilot study where patients with BE, without high
grade dysplasia, are treated with tamoxifen and assessed for changes in the appearance of
their BE by endoscopy and histology as well as changes in the SOX2/CDX2 ratio indicative of
an improvement in BE metaplasia

Inclusion Criteria:

- Biopsy-proven Barrett's esophagus that is non-dysplastic or with low grade dysplasia.

- At least 18 years of age.

- ECOG performance status ≤ 2

- Normal bone marrow and organ function as defined below:

- Absolute neutrophil count ≥1,500/mcl

- Platelets ≥ 100,000/mcl

- AST(SGOT)/ALT(SGPT) ≤1.5 x IULN

- Serum creatinine within normal institutional limits or less than the lower limit
of normal institutional limits; or creatinine clearance ≥ 60 mL/min/1.73 m2 for
patients with creatinine levels above institutional normal

- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) prior to study entry and
for the duration of study participation. Should a woman become pregnant or suspect
she is pregnant while participating in this study, she must inform her treating
physician immediately.

- Ability to understand and willingness to sign an IRB approved written informed
consent document.

Exclusion Criteria:

- Prior history of esophageal cancer.

- Prior history or current use of tamoxifen or anti-estrogen therapy.

- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to tamoxifen.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Pregnant and/or breastfeeding. Female patients must have a negative urine pregnancy
test within 14 days of study entry.

- Known HIV-positivity and on combination antiretroviral therapy because of the
potential for pharmacokinetic interactions with tamoxifen. Appropriate studies will
be undertaken in patients receiving combination antiretroviral therapy when
indicated.

- Taking medications known to affect drug metabolism via the CYP3A4, CYP2C9, or CYP2D6
pathways.

- History of blood clots (i.e. pulmonary embolism, DVTs).

- Concurrent use of anticoagulants (i.e. Coumadin/warfarin).