Ignite Creation Date:
2025-12-24 @ 7:15 PM
Ignite Modification Date:
2026-01-05 @ 5:30 PM
Study NCT ID:
NCT00474903
Status:
COMPLETED
Last Update Posted:
2014-07-02
First Post:
2007-05-16
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Esomeprazole Magnesium With or Without Aspirin in Preventing Esophageal Cancer in Patients With Barrett Esophagus
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
Randomized, Double-Blinded Phase II Trial of Esomeprazole Versus Esomeprazole + Two Doses of Aspirin in Barrett's Esophagus Patients
Status:
COMPLETED
Status Verified Date:
2014-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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. The use of esomeprazole magnesium with or without aspirin may help prevent esophageal cancer in patients with Barrett esophagus.
Detailed Description:
PRIMARY OBJECTIVES:
I. 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:
I. 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.
V. 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.
I. 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:
I. 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.
V. 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 Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?: