Tamoxifen to Treat Barrett's Metaplasia

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Washington University School of Medicine
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT02089386
First received: March 13, 2014
Last updated: July 8, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Barrett Metaplasia
Drug: Tamoxifen
Procedure: Endoscopy
Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Tamoxifen to Treat Barrett's Metaplasia

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Extent of Barrett's involvement and changes in histology [ Time Frame: End of 12 weeks (at the time of second endoscopy) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Changes in SOX2 and CDX2 expression [ Time Frame: End of 12 weeks (at the time of second endoscopy) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: July 2014
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tamoxifen
Tamoxifen 20 mg daily for 12 weeks
Drug: Tamoxifen
Other Names:
  • Nolvadex®
  • Soltamox®
Procedure: Endoscopy

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
    • Creatinine within 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02089386

Contacts
Contact: A. Craig Lockhart, M.D. 314-362-5740 alockhar@dom.wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: A. Craig Lockhart, M.D.    314-362-5740    alockhar@dom.wustl.edu   
Sub-Investigator: Jean Wang, M.D., Ph.D.         
Sub-Investigator: Jason Mills, M.D., Ph.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: A. Craig Lockhart, M.D. Washington University School of Medicine
  More Information

Additional Information:
Publications:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02089386     History of Changes
Other Study ID Numbers: 201404013
Study First Received: March 13, 2014
Last Updated: July 8, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Barrett Esophagus
Metaplasia
Digestive System Abnormalities
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Pathologic Processes
Tamoxifen
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Bone Density Conservation Agents
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Selective Estrogen Receptor Modulators
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014