A Phase III, Randomized, Study of Aspirin and Esomeprazole Chemoprevention in Barrett's Metaplasia (AspECT)

• ClinicalTrials.gov Identifier: NCT00357682
• Recruitment Status: Unknown
• First Posted: July 27, 2006
• Last Update Posted: May 18, 2016
• Sponsor: University of Oxford
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): University of Oxford

Tracking Information

• First Submitted Date: July 26, 2006
• First Posted Date: July 27, 2006
• Last Update Posted Date: May 18, 2016
• Study Start Date: March 2005
• Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 21, 2012): Conversion of Barrett's esophagus to adenocarcinoma of the esophagus or high-grade dysplasia [ Time Frame: assessed every 2 years ]
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures (submitted: February 21, 2012): All causes of mortality [ Time Frame: assessed annually ]
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase III, Randomized, Study of Aspirin and Esomeprazole Chemoprevention in Barrett's Metaplasia
• Official Title: A Phase III, Randomized, Study of Aspirin and Esomeprazole Chemoprevention in Barrett's Metaplasia

Brief Summary

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of esomeprazole and aspirin may prevent esophageal cancer in patients with Barrett's metaplasia. It is not yet known whether esomeprazole is more effective with or without aspirin in preventing esophageal cancer in patients with Barrett's metaplasia.

PURPOSE: This randomized phase III trial is studying esomeprazole with or without aspirin to compare how well they work in preventing esophageal cancer in patients with Barrett's metaplasia.

Detailed Description

PRIMARY OBJECTIVES

• To assess whether intervention with aspirin results in a decreased rate of all causes of mortality or conversion rate from Barrett's metaplasia to adenocarcinoma or high grade dysplasia.
• To assess whether high dose PPI (protein pump inhibitor) therapy results in a decreased rate of all causes of mortality or conversion rate from Barrett's metaplasia to adenocarcinoma or high grade dysplasia.

SECONDARY OBJECTIVES

• To assess whether intervention with aspirin results in decreased high-grade dysplasia, in decreased all cause mortality, in decreased oesophageal cancer incidence and in decreased cause-specific mortality when each is considered separately
• To assess whether intervention with high dose PPI results in decreased high-grade dysplasia, in decreased all cause mortality, in decreased oesophageal cancer incidence and in decreased cause-specific mortality when each is considered separately
• To assess whether there are clinical and molecular risk factors which can be identified in BM (Barrett's Metaplasia) for the development of BA.
• To assess the cost effectiveness of aspirin and/or PPI treatment in the prevention of BA.
• To assess whether intervention with PPI and/or aspirin induces changes in the expression of molecular markers for BA.
• To investigate new genes important in the progression of BA, as a unique tissue bank will be available with a complete endoscopic, histological, physiology and pharmaceutical history.
• To assess inherited genetic factors for predisposition to oesophagitis above BM, BM, LGD HGD and BA.
• To assess what the biological risk factors are for cardiac disease and aspirin resistance.
• To assess gender differences in outcomes.

Cancer Research UK approved the study in 2003 for a 10 year period to run from 1st January 2005 to 31st December 2014. Funding is renewable annually and is dependent on a satisfactory review by an independent committee.

An application for a funding extension will be made to CRUK 18 months before the end of the current grant.

A total of 2513 patients have been accrued for this study. They remain on trial medication and follow up.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Factorial Assignment; Masking: None (Open Label); Primary Purpose: Prevention

Condition

• Esophageal Cancer
• Precancerous Condition

Intervention

• Drug: Esomeprazole
  20mg per day
  Other Name: Nexium
• Drug: Esomeprazole
  80mg per day
  Other Name: Nexium
• Drug: Aspirin
  300mg per day

Study Arms

• Experimental: Arm A
  20mg Esomeprazole
  Intervention: Drug: Esomeprazole
• Experimental: Arm B
  80mg Esomeprazole
  Intervention: Drug: Esomeprazole
• Experimental: Arm C
  20mg Esomeprazole + 300mg Aspirin
  Interventions:

  • Drug: Esomeprazole
  • Drug: Aspirin
• Experimental: Arm D
  80mg Esomeprazole + 300mg Aspirin
  Interventions:

  • Drug: Esomeprazole
  • Drug: Aspirin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: February 21, 2012): 2513
• Original Enrollment: Not Provided
• Estimated Study Completion Date: May 2017
• Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

INCLUSION CRITERIA

1. Aged ≥18 years.
2. Circumferential Barrett's metaplasia of at least 1cm in length (≥C1M1) or a tongue of Barrett's metaplasia of at least 2cm in length (≥C0M2) (irrespective of the presence now or historically of histologically proven intestinal metaplasia).
3. Able to give written informed consent.
4. WHO performance status of 0 or 1 i.e. fully active and self-caring.

EXCLUSION CRITERIA

1. High grade dysplasia or carcinoma at enrolment.

2. Medical conditions which would make completing endoscopies or completing the trial difficult including:

   1. Frequent transient ischaemic attacks (3 or more) or severe cerebral vascular accident in the previous 6 months*
   2. Severe respiratory disease with arterial oxygen saturation less 90% at rest
   3. Severe ischaemic heart disease (exercise tolerance less than 100 yards or life expectancy < 4 years) or myocardial infarction in the previous 3 months
   4. Severe inflammatory bowel disease requiring at least one hospital admission of 5 days in the last year or bowels open > 6 times/day * Patients answering yes to criterion a. were eligible for the PPI-only (non-aspirin) arms of the trial
3. Continuous/frequent non-steroidal anti-inflammatory drug use or COX-2 inhibitors (more than 60 days per year in total).
4. Patients with absolute contraindications to PPIs, aspirin or their excipients i.e. allergies, ulcers, renal impairment or use of oral anticoagulants.
5. Pregnant or lactating women will not undergo endoscopy and may be given dispensation to stop drug therapy for a year. This should be discussed with the Trial Office.

If a patient was suitable for inclusion but later becomes unsuitable this should be discussed with the Trial Office before they are withdrawn. Only in exceptional circumstances should patients not be followed up i.e. withdrawal of consent or current life threatening disease with poor outcome and therefore unable to tolerate endoscopy. In these circumstances patients should be followed up in outpatient clinics.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT00357682
• Other Study ID Numbers: CDR0000491649; OCTO-003 ( Other Identifier: Oncology Clinical Trials Office ); 2004-003836-77 ( EudraCT Number ); ISRCTN85156844 ( Registry Identifier: ISRCTN )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: University of Oxford
• Study Sponsor: University of Oxford
• Collaborators: AstraZeneca

Investigators

• Principal Investigator: Janusz Jankowski, MD; Queen Mary University of London

• PRS Account: University of Oxford
• Verification Date: May 2016