Clinical trial NCT02089386: Tamoxifen to Treat Barrett's Metaplasia
Official title: Tamoxifen to Treat Barrett's Metaplasia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Barrett Metaplasia
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2014-03-17
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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 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 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
  * 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).

Primary outcomes:
measure: Extent of Barrett's involvement and changes in histology
timeFrame: End of 12 weeks (at the time of second endoscopy)
Secondary outcomes:
measure: Changes in SOX2 and CDX2 expression
timeFrame: End of 12 weeks (at the time of second endoscopy)
measure: Tolerance of tamoxifen
timeFrame: 4 months (30 days after cessation of tamoxifen or after second endoscopy - whichever occurs later)
measure: Changes in the length of Barrett's esophagus involvement
timeFrame: End of 12 weeks (at the time of second endoscopy)
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Jason Mills, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lindblad M, Garcia Rodriguez LA, Chandanos E, Lagergren J. Hormone replacement therapy and risks of oesophageal and gastric adenocarcinomas. Br J Cancer. 2006 Jan 16;94(1):136-41. doi: 10.1038/sj.bjc.6602906.
citation: Huh WJ, Khurana SS, Geahlen JH, Kohli K, Waller RA, Mills JC. Tamoxifen induces rapid, reversible atrophy, and metaplasia in mouse stomach. Gastroenterology. 2012 Jan;142(1):21-24.e7. doi: 10.1053/j.gastro.2011.09.050. Epub 2011 Oct 14.