Tamoxifen to Treat Barrett's Metaplasia

NCT02089386 | Terminated Early Phase 1 DMC FDA Drug

• 1 other identifier: 201404013
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Barrett Metaplasia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Changes in SOX2 and CDX2 expression

  End of 12 weeks (at the time of second endoscopy)

• Tolerance of tamoxifen

  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)

Study Arms (1)

Tamoxifen

EXPERIMENTAL

Tamoxifen 20 mg daily for 12 weeks

Drug: Tamoxifen; Procedure: Endoscopy

Interventions

Tamoxifen DRUG

Also known as: Nolvadex®, Soltamox®

Tamoxifen

Endoscopy PROCEDURE

Tamoxifen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (2)

• 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.

  PMID: 16404367 BACKGROUND

• 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.

  PMID: 22001866 BACKGROUND

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Barrett Esophagus

Interventions

Tamoxifen; Endoscopy

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diagnostic Techniques, Surgical; Diagnostic Techniques and Procedures; Diagnosis; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Jason Mills, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2014
• First Posted: March 17, 2014
• Study Start: July 9, 2014
• Primary Completion: June 21, 2016
• Study Completion: June 21, 2016
• Last Updated: March 13, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)