Tamoxifen to Treat Barrett's Metaplasia

March 9, 2017 updated by: Washington University School of Medicine
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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tamoxifen
Tamoxifen 20 mg daily for 12 weeks
Drug: Tamoxifen
Other Names:
  • Nolvadex®
  • Soltamox®
Procedure: Endoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Extent of Barrett's involvement and changes in histology
Time Frame: End of 12 weeks (at the time of second endoscopy)
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
Time Frame: End of 12 weeks (at the time of second endoscopy)
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
Time Frame: 4 months (30 days after cessation of tamoxifen or after second endoscopy - whichever occurs later)
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
Time Frame: End of 12 weeks (at the time of second endoscopy)
End of 12 weeks (at the time of second endoscopy)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Investigators

  • Principal Investigator: Jason Mills, M.D., Ph.D., Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 9, 2014

Primary Completion (Actual)

June 21, 2016

Study Completion (Actual)

June 21, 2016

Study Registration Dates

First Submitted

March 13, 2014

First Submitted That Met QC Criteria

March 13, 2014

First Posted (Estimate)

March 17, 2014

Study Record Updates

Last Update Posted (Actual)

March 13, 2017

Last Update Submitted That Met QC Criteria

March 9, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201404013

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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