Barrett EsophagusPhase 2NCT00474903
Esomeprazole Magnesium With or Without Aspirin in Preventing Esophageal Cancer in Patients With Barrett Esophagus
A Phase 2 study testing acetylsalicylic acid and esomeprazole magnesium in people with Barrett Esophagus and Esophageal Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This randomized phase II trial is studying the effect of esomeprazole magnesium and aspirin on tissue PGE2 levels compared with esomeprazole and placebo. This type of chemoprevention treatment investigates the use of certain drugs to assess whether they assist in the prevention of cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Barrett Esophagus, Esophageal Cancer
- What is being tested?
- acetylsalicylic acid and esomeprazole magnesium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 122 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2007to Jun 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Histologically confirmed Barrett esophagus, meeting all of the following criteria:
- Presence of specialized columnar epithelium anywhere in the tubular esophagus with ≥ 2 cm of circumferential involvement
- No evidence of high-grade dysplasia or cancer by esophagogastroduodenoscopy (EGD)
- No prior histologically confirmed esophageal dysplasia, including cancer
- Adequate Barrett mucosa, defined as ≥ 4 of 8 research samples with≥ 50% intestinal metaplasia in research biopsies
- No ulcer, erosion, plaque, nodule, stricture, or other luminal irregularity within the Barrett's segment or erosive esophagitis (Los Angeles classification > grade A) detected at pre-intervention EGD exam
Show all 40Show fewer
- Eastern Cooperative Group (ECOG) performance status 0-2
- Hemoglobin normal
- Platelet count ≥ 100,000/mm³
- Aspartate aminotransferase (AST) ≤ 2.5 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 2.5 times ULN
- Bilirubin ≤ 2.5 times ULN
- Creatinine ≤ 2.5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No nasal polyps associated with asthma or induced or exacerbated by aspirin
- No malignancy within the past 5 years except for nonmelanoma skin cancer
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to the study agents or rescue medication
- No history of endoscopically or radiographically diagnosed peptic ulcer disease (bleeding or nonbleeding)
- No other uncontrolled illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Bleeding disorder
- Vitamin K deficiency
- Alcohol abuse (defined as ingestion of ≥ 3 drinks per day)
- Psychiatric illness or social situations that would limit study compliance
- At least 3 months since prior chronic use (defined as ≥ 7 days during the 3 months preceding the beginning of the Run-in phase) of acetylsalicylic acid (aspirin), nonsteroidal antiinflammatory drug (NSAIDs), or selective cyclooxygenase (COX-2) inhibitors
- At least 3 months since prior investigational agents except innocuous agents with no known interaction with the study agents (e.g., standard dose multivitamins or topical agents for limited skin conditions)
- No prior fundoplication, bariatric surgery, or any other major upper gastrointestinal surgery
- Prior cholecystectomy allowed
- No other concurrent NSAIDs (including aspirin) or selective COX-2 inhibitor therapy
- No concurrent anticoagulant drugs including, but not limited to, any of the following:
- Warfarin
- Heparin
- Low-molecular weight heparin
- Clopidogrel bisulfate
- Extended-release dipyridamole
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized, Double-Blinded Phase II Trial of Esomeprazole Versus Esomeprazole + Two Doses of Aspirin in Barrett's Esophagus Patients
This randomized phase II trial is studying the effect of esomeprazole magnesium and aspirin on tissue PGE2 levels compared with esomeprazole and placebo. This type of chemoprevention treatment investigates the use of certain drugs to assess whether they assist in the prevention of cancer. The use of esomeprazole magnesium with or without aspirin may help prevent esophageal cancer in patients with Barrett esophagus.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the effects of a 28 day intervention with aspirin 81 mg placebo orally (PO) once daily (QD) + aspirin 325 mg placebo PO QD + esomeprazole 40 mg PO BID versus aspirin 81 mg PO QD + aspirin 325 mg placebo PO QD + esomeprazole 40 mg PO BID versus aspirin 325 mg PO QD + aspirin 81 mg placebo PO QD + esomeprazole 40 mg PO BID on the absolute change in tissue prostaglandin E2 (PGE2) concentration, as determined from Barrett's esophagus mucosal biopsy samples obtained pre- and post-intervention (i.e. two pair-wise comparisons of two different doses of active aspirin regimens versus aspirin placebo group), Specifically, the two active aspirin + esomeprazole arms will be independently analyzed to see if they significantly reduce the mean tissue PGE2 concentration from Pre- to Post-intervention as compared to the aspirin placebo + esomeprazole arm.
SECONDARY OBJECTIVES:
- To determine if the change in the tissue PGE2 concentration decreases significantly in the aspirin placebo + esomeprazole arm.
II. To compare the change in mean tissue PGE2 concentration between the two active intervention arms to determine which one appears the most promising for further testing.
III. To assess the effects of the three agents (arms) with respect to proliferation (Ki-67), apoptosis (caspase-3 expression), COX-2 expression, and p16 methylation using Pre- and Post-Intervention biopsy samples obtained from Barrett's mucosal tissue.
IV. To evaluate all adverse events associated with each of the three intervention arms.
- To provide exploratory summaries of PGE2 concentration values by patient subgroups of interest.
VI. To provide descriptive summaries of the esophagogastroduodenoscopy (EGD) results, the rate of dysplasia, adverse events, and the Run-In Agent compliance on all participants that signed a consent form and started the Run-In phase of the trial.
VII. To establish a biospecimen repository archive for future correlative studies.
OUTLINE: This is a multicenter, randomized, double-blind, placebo-controlled study. Patients are stratified according to dysplasia status, gender, and length of Barrett segment of circumferential involvement (5 cm vs = 5 cm). Patients are randomized to 1 of 3 treatment arms.
ARM I: Patients receive two oral placebos once daily and oral esomeprazole magnesium twice daily.
ARM II: Patients receive oral acetylsalicylic acid (aspirin) and oral placebo once daily and oral esomeprazole magnesium twice daily.
ARM III: Patients receive a higher-dose of oral aspirin (higher than in arm II) and a lower-dose of oral placebo (lower than in arm II) once daily and oral esomeprazole magnesium twice daily.
In all arms, treatment continues for 28 days in the absence of unacceptable toxicity. Tissue samples are collected before and after treatment and examined for tissue-based biomarkers (i.e., PGE_2, Ki-67, caspase-3 apoptosis, and cyclooxygenase-2) by immunohistochemistry, enzyme immunoassay, Western blot, and polymerase chain reaction.
After completion of study therapy, patients are followed 7 - 30 days.
- Conditions
- Barrett Esophagus, Esophageal Cancer
- Being tested
- acetylsalicylic acid, esomeprazole magnesium, placebo
- Medical subject headings
- Barrett Esophagus, Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
acetylsalicylic acidDrug
Given orally
esomeprazole magnesiumDrug
Given orally
placeboOther
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Arm I (placebo, esomeprazole magnesium) | Active comparator | Patients receive two oral placebos once daily and oral esomeprazole magnesium (40 mg, twice daily). Receives: Drug: esomeprazole magnesium; Other: placebo |
| Arm II (low-dose aspirin, esomeprazole magnesium) | Experimental | Patients receive both an oral placebo and acetylsalicylic acid (81 mg dose), once daily and oral esomeprazole magnesium (40 mg, twice daily). Receives: Drug: acetylsalicylic acid; Drug: esomeprazole magnesium; Other: placebo |
| Arm III (higher-dose aspirin, esomeprazole magnesium) | Experimental | Patients receive both an oral placebo and acetylsalicylic acid (325 mg dose), once daily and oral esomeprazole magnesium (40 mg, twice daily). Receives: Drug: acetylsalicylic acid; Drug: esomeprazole magnesium; Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Mean Tissue Prostaglandin E2 (PGE2) Concentration as Determined From Barrett's Research Mucosal Biopsy Samples
The mean tissue PGE2 is reported for each Arm.
Measured: Baseline to 30 days after completion of study treatment
Secondary outcomes (1)
Toxicity
Toxicity is defined as adverse events that are classified as either possibly, probably, or definitely related to the interventional agent, graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The number of patients reporting adverse events will be tabulated by grade.
Measured: Up to 30 days after completion of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2007 (estimated)
- Study startApr 2007
- Primary completionMar 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Barrett EsophagusStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Paul Limburg, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00474903
- Sponsor's protocol ID
- NCI-2009-00838
- Other IDs
- NCI-2009-00838, MAY04-4-01, CDR0000544180, MAYO-MAY04-4-01, MAY04-4-01, N01CN35000
- Status last verified
- Jan 2014
- First submitted
- 16 May 2007
- Last updated
- 2 Jul 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Falk GW, Buttar NS, Foster NR, Ziegler KL, Demars CJ, Romero Y, Marcon NE, Schnell T, Corley DA, Sharma P, Cruz-Correa MR, Hur C, Fleischer DE, Chak A, Devault KR, Weinberg DS, Della'Zanna G, Richmond E, Smyrk TC, Mandrekar SJ, Limburg PJ; Cancer Prevention Network. A combination of esomeprazole and aspirin reduces tissue concentrations of prostaglandin E(2) in patients with Barrett's esophagus. Gastroenterology. 2012 Oct;143(4):917-26.e1. doi: 10.1053/j.gastro.2012.06.044. Epub 2012 Jul 11.
PubMed 22796132
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double-Blinded Phase II Trial of Esomeprazole Versus Esomeprazole + Two Doses of Aspirin in Barrett's Esophagus Patients
- ClinicalTrials.gov ID
- NCT00474903
- Acronym / sponsor ID
- NCI-2009-00838
- Conditions
- Barrett Esophagus, Esophageal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 122 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Apr 2007
- Primary completion
- Mar 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 17 May 2007 (estimated)
- Results
- Posted 2 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase II trial is studying the effect of esomeprazole magnesium and aspirin on tissue PGE2 levels compared with esomeprazole and placebo. This type of chemoprevention treatment investigates the use of certain drugs to assess whether they assist in the prevention of cancer. The use of esomeprazole magnesium with or without aspirin may help prevent esophageal cancer in patients with Barrett esophagus.
Detailed description
PRIMARY OBJECTIVES:
- To assess the effects of a 28 day intervention with aspirin 81 mg placebo orally (PO) once daily (QD) + aspirin 325 mg placebo PO QD + esomeprazole 40 mg PO BID versus aspirin 81 mg PO QD + aspirin 325 mg placebo PO QD + esomeprazole 40 mg PO BID versus aspirin 325 mg PO QD + aspirin 81 mg placebo PO QD + esomeprazole 40 mg PO BID on the absolute change in tissue prostaglandin E2 (PGE2) concentration, as determined from Barrett's esophagus mucosal biopsy samples obtained pre- and post-intervention (i.e. two pair-wise comparisons of two different doses of active aspirin regimens versus aspirin placebo group), Specifically, the two active aspirin + esomeprazole arms will be independently analyzed to see if they significantly reduce the mean tissue PGE2 concentration from Pre- to Post-intervention as compared to the aspirin placebo + esomeprazole arm.
SECONDARY OBJECTIVES:
- To determine if the change in the tissue PGE2 concentration decreases significantly in the aspirin placebo + esomeprazole arm.
II. To compare the change in mean tissue PGE2 concentration between the two active intervention arms to determine which one appears the most promising for further testing.
III. To assess the effects of the three agents (arms) with respect to proliferation (Ki-67), apoptosis (caspase-3 expression), COX-2 expression, and p16 methylation using Pre- and Post-Intervention biopsy samples obtained from Barrett's mucosal tissue.
IV. To evaluate all adverse events associated with each of the three intervention arms.
- To provide exploratory summaries of PGE2 concentration values by patient subgroups of interest.
VI. To provide descriptive summaries of the esophagogastroduodenoscopy (EGD) results, the rate of dysplasia, adverse events, and the Run-In Agent compliance on all participants that signed a consent form and started the Run-In phase of the trial.
VII. To establish a biospecimen repository archive for future correlative studies.
OUTLINE: This is a multicenter, randomized, double-blind, placebo-controlled study. Patients are stratified according to dysplasia status, gender, and length of Barrett segment of circumferential involvement (5 cm vs = 5 cm). Patients are randomized to 1 of 3 treatment arms.
ARM I: Patients receive two oral placebos once daily and oral esomeprazole magnesium twice daily.
ARM II: Patients receive oral acetylsalicylic acid (aspirin) and oral placebo once daily and oral esomeprazole magnesium twice daily.
ARM III: Patients receive a higher-dose of oral aspirin (higher than in arm II) and a lower-dose of oral placebo (lower than in arm II) once daily and oral esomeprazole magnesium twice daily.
In all arms, treatment continues for 28 days in the absence of unacceptable toxicity. Tissue samples are collected before and after treatment and examined for tissue-based biomarkers (i.e., PGE_2, Ki-67, caspase-3 apoptosis, and cyclooxygenase-2) by immunohistochemistry, enzyme immunoassay, Western blot, and polymerase chain reaction.
After completion of study therapy, patients are followed 7 - 30 days.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm I (placebo, esomeprazole magnesium) | Active comparator | Drug: esomeprazole magnesium, Other: placeboPatients receive two oral placebos once daily and oral esomeprazole magnesium (40 mg, twice daily). |
| Arm II (low-dose aspirin, esomeprazole magnesium) | Experimental | Drug: acetylsalicylic acid, Drug: esomeprazole magnesium, Other: placeboPatients receive both an oral placebo and acetylsalicylic acid (81 mg dose), once daily and oral esomeprazole magnesium (40 mg, twice daily). |
| Arm III (higher-dose aspirin, esomeprazole magnesium) | Experimental | Drug: acetylsalicylic acid, Drug: esomeprazole magnesium, Other: placeboPatients receive both an oral placebo and acetylsalicylic acid (325 mg dose), once daily and oral esomeprazole magnesium (40 mg, twice daily). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (40 listed)
- Histologically confirmed Barrett esophagus, meeting all of the following criteria:
- Adequate Barrett mucosa, defined as ≥ 4 of 8 research samples with≥ 50% intestinal metaplasia in research biopsies
- No ulcer, erosion, plaque, nodule, stricture, or other luminal irregularity within the Barrett's segment or erosive esophagitis (Los Angeles classification > grade A) detected at pre-intervention EGD exam
- Eastern Cooperative Group (ECOG) performance status 0-2
- Hemoglobin normal
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| acetylsalicylic acidGiven orally | Drug | Arm II (low-dose aspirin, esomeprazole magnesium), Arm III (higher-dose aspirin, esomeprazole magnesium) |
| esomeprazole magnesiumGiven orally | Drug | Arm I (placebo, esomeprazole magnesium), Arm II (low-dose aspirin, esomeprazole magnesium), Arm III (higher-dose aspirin, esomeprazole magnesium) |
| placeboGiven orally | Other | Arm I (placebo, esomeprazole magnesium), Arm II (low-dose aspirin, esomeprazole magnesium), Arm III (higher-dose aspirin, esomeprazole magnesium) |
Primary outcome
Change in Mean Tissue Prostaglandin E2 (PGE2) Concentration as Determined From Barrett's Research Mucosal Biopsy Samples
Time frame: Baseline to 30 days after completion of study treatment
The mean tissue PGE2 is reported for each Arm.
1 secondary outcome
Toxicity
Time frame: Up to 30 days after completion of study treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22796132Falk GW, Buttar NS, Foster NR, Ziegler KL, Demars CJ, Romero Y, Marcon NE, Schnell T, Corley DA, Sharma P, Cruz-Correa MR, Hur C, Fleischer DE, Chak A, Devault KR, Weinberg DS, Della'Zanna G, Richmond E, Smyrk TC, Mandrekar SJ, Limburg PJ; Cancer Prevention Network. A combination of esomeprazole and aspirin reduces tissue concentrations of prostaglandin E(2) in patients with Barrett's esophagus. Gastroenterology. 2012 Oct;143(4):917-26.e1. doi: 10.1053/j.gastro.2012.06.044. Epub 2012 Jul 11.
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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.
Paul Limburg principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing acetylsalicylic acid and esomeprazole magnesium in people with Barrett Esophagus and Esophageal Cancer, run by National Cancer Institute (NCI) 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 40 inclusion and 0 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: finished, as of the sponsor's last update on 2 Jul 2014. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Mean Tissue Prostaglandin E2 (PGE2) Concentration as Determined From Barrett's Research Mucosal Biopsy Samples (time frame: Baseline to 30 days after completion of study treatment). 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 NCT00474903, which also lists 1 linked publication.
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 2 Jul 2014.