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

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.

Study Overview

• Status: Unknown
• Conditions: Esophageal Cancer; Precancerous Condition
• Intervention / Treatment: Drug: Esomeprazole; Drug: Esomeprazole; Drug: Aspirin

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
• Enrollment (Actual): 2513
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; 20mg Esomeprazole	Drug: Esomeprazole; 20mg per day; Other Names: Nexium; Drug: Esomeprazole; 80mg per day; Other Names: Nexium
Experimental: Arm B; 80mg Esomeprazole	Drug: Esomeprazole; 20mg per day; Other Names: Nexium; Drug: Esomeprazole; 80mg per day; Other Names: Nexium
Experimental: Arm C; 20mg Esomeprazole + 300mg Aspirin	Drug: Esomeprazole; 20mg per day; Other Names: Nexium; Drug: Esomeprazole; 80mg per day; Other Names: Nexium; Drug: Aspirin; 300mg per day
Experimental: Arm D; 80mg Esomeprazole + 300mg Aspirin	Drug: Esomeprazole; 20mg per day; Other Names: Nexium; Drug: Esomeprazole; 80mg per day; Other Names: Nexium; Drug: Aspirin; 300mg per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Conversion of Barrett's esophagus to adenocarcinoma of the esophagus or high-grade dysplasia	assessed every 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
All causes of mortality	assessed annually

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Janusz Jankowski, MD, Queen Mary University of London

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (Anticipated): May 1, 2017
• Study Completion (Anticipated): May 1, 2017

Study Registration Dates

• First Submitted: July 26, 2006
• First Submitted That Met QC Criteria: July 26, 2006
• First Posted (Estimate): July 27, 2006

Study Record Updates

• Last Update Posted (Estimate): May 18, 2016
• Last Update Submitted That Met QC Criteria: May 17, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: esophageal cancer; Barrett's esophagus
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Barrett Esophagus; Precancerous Conditions; Metaplasia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Aspirin; Esomeprazole
• Other Study ID Numbers: CDR0000491649; OCTO-003 (Other Identifier: Oncology Clinical Trials Office); 2004-003836-77 (EudraCT Number); ISRCTN85156844 (Registry Identifier: ISRCTN)