Barrett MetaplasiaEarly Phase 1NCT02089386
Tamoxifen to Treat Barrett's Metaplasia
A Early Phase 1 study testing Tamoxifen and Endoscopy in people with Barrett Metaplasia, run by Washington University School of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Barrett Metaplasia
- What is being tested?
- Tamoxifen and Endoscopy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Jul 2014to 21 Jun 2016
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
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.
Read the 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
- Conditions
- Barrett Metaplasia
- Being tested
- Tamoxifen, Endoscopy
- Medical subject headings
- Barrett Esophagus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TamoxifenDrug
Also called Nolvadex®, Soltamox®
EndoscopyProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Tamoxifen | Experimental | Tamoxifen 20 mg daily for 12 weeks Receives: Drug: Tamoxifen; Procedure: Endoscopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: End of 12 weeks (at the time of second endoscopy)
Secondary outcomes (3)
Changes in SOX2 and CDX2 expression
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.
Measured: End of 12 weeks (at the time of second endoscopy)
Tolerance of tamoxifen
As measured by toxicities using CTCAE version 4.0
Measured: 4 months (30 days after cessation of tamoxifen or after second endoscopy - whichever occurs later)
Changes in the length of Barrett's esophagus involvement
Measured: End of 12 weeks (at the time of second endoscopy)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2014 (estimated)
- Study start9 Jul 2014
- Primary completion21 Jun 2016
- Study completion21 Jun 2016
Why it stopped: Insufficient funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Barrett MetaplasiaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jason Mills, M.D., Ph.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02089386
- Sponsor's protocol ID
- 201404013
- Status last verified
- Mar 2017
- First submitted
- 13 Mar 2014
- Last updated
- 13 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 16404367Huh 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.
PubMed 22001866
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tamoxifen to Treat Barrett's Metaplasia
- ClinicalTrials.gov ID
- NCT02089386
- Acronym / sponsor ID
- 201404013
- Conditions
- Barrett Metaplasia
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient funding
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 9 Jul 2014 (actual)
- Primary completion
- 21 Jun 2016 (actual)
- Study completion
- 21 Jun 2016 (actual)
- First posted
- 17 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tamoxifen | Experimental | Drug: Tamoxifen, Procedure: EndoscopyTamoxifen 20 mg daily for 12 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TamoxifenAlso: Nolvadex®, Soltamox® | Drug | Tamoxifen |
| Endoscopy | Procedure or surgery | Tamoxifen |
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.
3 secondary outcomes
Changes in SOX2 and CDX2 expression
Time frame: 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)
Changes in the length of Barrett's esophagus involvement
Time frame: End of 12 weeks (at the time of second endoscopy)
Results and safety
The study was stopped early (reason given: Insufficient funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2017.
- Background: PubMed 16404367Lindblad 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.
- Background: PubMed 22001866Huh 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.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jason Mills, M.D., Ph.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Tamoxifen and Endoscopy in people with Barrett Metaplasia, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Insufficient funding). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Extent of Barrett's involvement and changes in histology (time frame: End of 12 weeks (at the time of second endoscopy)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02089386, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2017.