Clinical Trial: Tamoxifen to Treat Barrett's Metaplasia

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Tamoxifen to Treat Barrett's Metaplasia

Brief Summary: 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 Summary: 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
Sponsor: Washington University School of Medicine

Current Primary Outcome: 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.


Original Primary Outcome:

  • Changes in SOX2 and CDX2 expression [ Time Frame: 4 months ]
    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.
  • Extent of Barrett's involvement and changes in histology [ Time Frame: 4 months ]
    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: 1) changes in the length of Barrett's esophagus involvement; and 2) the specific studies included to assess the response to tamoxifen.


Current Secondary Outcome:

  • 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.
  • 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
  • Changes in the length of Barrett's esophagus involvement [ Time Frame: End of 12 weeks (at the time of second endoscopy) ]


Original Secondary Outcome: Tolerance of tamoxifen [ Time Frame: 4 months ]

Assess the tolerance of tamoxifen in this patient population as measured by CTCAE version 4.0


Information By: Washington University School of Medicine

Dates:
Date Received: March 13, 2014
Date Started: July 9, 2014
Date Completion:
Last Updated: March 9, 2017
Last Verified: March 2017