Tamoxifen to Treat Barrett's Metaplasia

Study Overview
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Brief Summary
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Treat Barrett's esophagus (BE) patients with tamoxifen to Barrett's metaplasia as measured by changes in Barrett's esophagus appearance by endoscopy and histology as well as changes in SOX2 and CDX2.

Detailed Description
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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

Official Title
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Tamoxifen to Treat Barrett's Metaplasia

Conditions
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Barrett Metaplasia

Intervention / Treatment
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* Drug: Tamoxifen
* Procedure: Endoscopy


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tamoxifen<br>Tamoxifen 20 mg daily for 12 weeks | Drug: Tamoxifen<br> <br> * Other names: Soltamox®;Procedure: Endoscopy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extent of Barrett's involvement and changes in histology | The biopsy procedures with 4 quadrant biopsies/2 cm for histology and additional biopsies for freezing for macromolecular analysis to assess the preliminary diagnostic value of this marker pair in identifying levels of metaplasia in BE and as an indicator of response to tamoxifen treatment. The tissue from the two endoscopic procedures will be assessed for changes in the following related to tamoxifen therapy. | End of 12 weeks (at the time of second endoscopy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in SOX2 and CDX2 expression | The main outcome measurements are SOX2 and CDX2, analyzed as a ratio. We will use a one sample paired non-parametric Wilcoxon test to test the significant difference if the ratio difference is not normally distributed. Normality assumption can be examined by visual Q-Q plot and formal Kolmogorov-Smirnov statistic. In addition, we will explore the patient level characteristics on treatment effect using a linear regression model. Specifically, we will use the difference ratio as the response variable and patient characteristics of interest as explanatory variables. Regression coefficients associated with the explanatory variables quantify the effect of these variables on the difference ratio, with t or F statistic testing for the statistical significance. | End of 12 weeks (at the time of second endoscopy) | 
| Tolerance of tamoxifen | As measured by toxicities using CTCAE version 4.0 | 4 months (30 days after cessation of tamoxifen or after second endoscopy - whichever occurs later) | 
| Changes in the length of Barrett's esophagus involvement |  | End of 12 weeks (at the time of second endoscopy) |