Clinical Trial: Aspirin in Preventing Disease Recurrence in Patients With Barrett Esophagus After Successful Elimination by Radiofrequency Ablation

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Effect of Aspirin on Biomarkers of Barrett's Esophagus After Successful Eradication of Barrett's Esophagus With Radiofrequency Ablation

Brief Summary: This randomized phase II trial studies the safety of and how well aspirin works in preventing Barrett's esophagus from returning after it has been successfully eliminated by radiofrequency ablation. Studying samples of tissue from patients with Barrett's esophagus for the levels of a specific protein that is linked to developing Barrett's esophagus may help doctors learn whether aspirin can prevent it from returning after it has been successfully treated.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To conduct a randomized, double blind, placebo-controlled phase II chemoprevention trial, investigating whether supplementation with aspirin 325 mg/day for 12 months is safe and reduces the expression of CDX2 messenger ribonucleic acid (mRNA) (a biomarker which has been associated with the risk of developing Barrett's esophagus [BE]) in comparison to placebo after successful radiofrequency ablation (RFA).

SECONDARY OBJECTIVES:

I. To assess safety at 12 months. II. To assess differences in the expression of CDX2 at 18 months, activation status of NF-kB by assessing levels of total and phosphorylated (phospho)-p65 and cytoplasmic to nuclear translocation of phospho-p65 which is likely to be affected by aspirin.

III. To assess the prostanoid marker, prostaglandin E2, and prostaglandin synthases, which are known to respond to aspirin and to correlation with clinicopathological factors in the esophageal cancer.

IV. To assess differences in the expression of proinflammatory cytokines known to induce activation of NFkB, i.e., TNFalpha, IL-1beta, IL-6, IL-10, IL-17A, IL-23 will be measured.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive aspirin orally (PO) once daily (QD) for 12 months.

ARM B: Patients receive placebo PO QD for 12 months.

After completion of study treatment, patients are followed up at 1, 3, 6, 9, 12, and 18 months.

Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Differences in the change of CDX2 mRNA levels in esophageal squamous tissue between participants taking aspirin supplementation versus those taking placebo [ Time Frame: Baseline to 12 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Change in well-being, as measured by the 36-Item Short Form Health Survey [ Time Frame: Baseline to 12 months ]
  Bivariate analyses will be performed on study entry and completion of the on-drug period. Multivariate analyses will be performed between groups after controlling for potential confounders.
• Differences in the activation status of NF-kB by assessing levels of total and phospho-p65 and cytoplasmic to nuclear translocation of phospho-p65 [ Time Frame: Baseline up to 18 months ]
  Both parametric (t-test) and non-parametric (Wilcoxon) tests will be performed.
• Differences in the change of CDX2 mRNA levels in esophageal squamous tissue between participants taking aspirin supplementation versus those taking placebo [ Time Frame: Baseline to 18 months ]
  Both parametric (t-test) and non-parametric (Wilcoxon) tests will be performed.
• Differences in the expression of proinflammatory cytokines known to induce activation of NFkB [ Time Frame: Baseline up to 18 months ]
  Both parametric (t-test) and non-parametric (Wilcoxon) tests will be performed.
• Differences in the prostanoid marker, prostaglandin E2, and prostaglandin synthases [ Time Frame: Baseline up to 18 months ]
  Both parametric (t-test) and non-parametric (Wilcoxon) tests will be performed.
• Incidence of adverse events, assessed according to the Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 18 months ]
  All adverse events will be recorded and graded during clinical visits, whether or not they are considered drug related. Each treatment arm will be monitored separately for severe toxicities (grade 3 and 4 severe adverse events). At the completion of the study, the frequency of toxicities will be compared between the placebo and aspirin groups.

Original Secondary Outcome:

• Change in well-being, as measured by the 36-Item Short Form Health Survey [ Time Frame: Baseline to 12 months ]
  Bivariate analyses will be performed on study entry and completion of the on-drug period. Multivariate analyses will be performed between groups after controlling for potential confounders.
• Differences in the activation status of NF-kB by assessing levels of total and phospho-p65 and cytoplasmic to nuclear translocation of phospho-p65 [ Time Frame: Up to 18 months ]
  Both parametric (t-test) and non-parametric (Wilcoxon) tests will be performed.
• Differences in the change of CDX2 mRNA levels in esophageal squamous tissue between participants taking aspirin supplementation versus those taking placebo [ Time Frame: Baseline to 18 months ]
  Both parametric (t-test) and non-parametric (Wilcoxon) tests will be performed.
• Differences in the expression of proinflammatory cytokines known to induce activation of NFkB [ Time Frame: Up to 18 months ]
  Both parametric (t-test) and non-parametric (Wilcoxon) tests will be performed.
• Differences in the prostanoid marker, prostaglandin E2 [ Time Frame: Up to 18 months ]
  Both parametric (t-test) and non-parametric (Wilcoxon) tests will be performed.
• Incidence of adverse events, assessed according to the Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 18 months ]
  All adverse events will be recorded and graded during clinical visits, whether or not they are considered drug related. Each treatment arm will be monitored separately for severe toxicities (grade 3 and 4 severe adverse events). At the completion of the study, the frequency of toxicities will be compared between the placebo and aspirin groups.

Information By: National Cancer Institute (NCI)

Dates:
Date Received: August 11, 2015
Date Started: January 2016
Date Completion:
Last Updated: May 11, 2017
Last Verified: May 2017