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Add-Aspirin: A Trial Assessing the Effects of Aspirin on Disease Recurrence and Survival After Primary Therapy in Common Non Metastatic Solid Tumours

Phase 3
Recruiting
Conditions
Breast Cancer
Colorectal Cancer
Cancer
Prostate Cancer
Gastro-oesophageal Cancer
Interventions
Drug: Placebo 300mg
Drug: Placebo 100mg
Registration Number
NCT02804815
Lead Sponsor
University College, London
Brief Summary

Add-Aspirin aims to assess whether regular aspirin use after standard curative therapy can prevent recurrence and improve survival in individuals with non-metastatic common tumours. The question will be assessed in four different tumour types (breast, colorectal, gastro-oesophageal and prostate) by means of parallel cohorts within an overarching trial protocol.

Eligible participants will be randomly assigned (double-blind) to either aspirin 100mg, aspirin 300mg or a matched placebo, to be taken daily for at least 5 years. Disease recurrence and survival will be assessed, along with adherence, toxicity, and other potential effects of aspirin (eg. cardiovascular).

There is a large body of evidence indicating that aspirin has anti-cancer effects. Meta-analyses of cardiovascular trials of aspirin have shown short-term effects on cancer mortality and a decrease in risk of metastases, suggesting a role for aspirin in the treatment as well as prevention of cancer. Additionally, large observational studies of individuals taking aspirin after cancer treatment have shown improved disease-specific and overall mortality for specific tumour types.

In the treatment setting, the risks of side effects associated with aspirin are expected to be outweighed by potential benefits. However, this has not yet been assessed in a randomised trial.

As a low cost, generic and widely available drug, which is generally safe, if aspirin is shown to be effective, it could have a huge impact on cancer outcomes globally.

Detailed Description

A phase III, multi-centre, double-blind, placebo-controlled randomised trial which aims to assess whether regular aspirin use after standard therapy prevents recurrence and prolongs survival in participants with non-metastatic common solid tumours.

The trial has four parallel tumour site-specific cohorts (breast, colorectal, gastro-oesophageal and prostate cancer). An overarching protocol ensures each cohort is as comparable as possible to allow a combined analysis of overall survival as a co-primary outcome measure in addition to individual tumour site-specific analyses of disease recurrence and survival.

Participants who have undergone potentially curative treatment (surgery or other radical treatment), including any standard neo-adjuvant or adjuvant therapy for breast, colorectal, gastro-oesophageal or prostate cancer or have participated in any pre-approved trials and satisfy the eligibility criteria.

Participants will be randomly assigned to 100mg aspirin, 300mg aspirin or matched placebo. All tablets will be enteric-coated to be taken daily for at least five years. Prior to randomisation, all potential participants will take open-label 100mg aspirin daily for a run-in period of approximately 8 weeks to assess tolerability and adherence.

The trial incorporates a feasibility phase during which recruitment feasibility, treatment adherence, safety and use of the run-in period will be assessed.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
11000
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Aspirin 300mgAspirin 300mgAspirin 300mg
Placebo 300mgPlacebo 300mg300mg Placebo
Placebo 100mgPlacebo 100mg100mg Placebo
Aspirin 100mgAspirin 100mgAspirin 100mg
Primary Outcome Measures
NameTimeMethod
Overall Survival10 years follow up

Overall survival of all cohorts combined

Biochemical recurrence-free survival (bRFS)5 years follow up

bRFS in the prostate cancer cohort

Disease-free survival (DFS)6 years follow up

DFS in the colorectal cancer cohort

Invasive disease-free survival (IDFS)6 years follow up

IDFS in the breast cancer cohort

Overall survival5 years follow up

Overall survival in the gastro-oesophageal cancer cohort

Secondary Outcome Measures
NameTimeMethod
Number of participants with second malignancies as assessed by case report form5 years follow up
Number of participants that show a decline in cognition and extent of decline as assessed by the Montreal Cognitive Assessment (MoCA)5 years follow up
Adherence5 years follow up

Patient-reported compliance (via diary card) will be assessed during the run-in period

Number of participants with serious haemorrhage (grade 3 or above) as measured by CTCAE V4.0. Data will be collected on case report forms.5 years follow up
Number of participants with treatment-related (active drug and placebo) cardiovascular events as assessed by CTCAE v4.05 years follow up

Trial Locations

Locations (82)

Christie Hospital

🇬🇧

Manchester, United Kingdom

Bon Secours Hospital

🇮🇪

Cork, Ireland

Mater Misericordiae University Hospital

🇮🇪

Dublin, Ireland

Mater Private Hospital

🇮🇪

Dublin, Ireland

St Luke's Hospital

🇮🇪

Dublin, Ireland

St Vincent's Hospital

🇮🇪

Dublin, Ireland

University College Hospital Galway

🇮🇪

Galway, Ireland

University Hospital Limerick

🇮🇪

Limerick, Ireland

Sligo University Hospital

🇮🇪

Sligo, Ireland

University Hospital Waterford

🇮🇪

Waterford, Ireland

Bedford Hospital

🇬🇧

Bedford, United Kingdom

Bristol Haematology & Oncology Centre

🇬🇧

Bristol, United Kingdom

West Suffolk Hospital

🇬🇧

Bury St Edmunds, United Kingdom

Fairfield Hospital

🇬🇧

Bury, United Kingdom

Velindre Hospital

🇬🇧

Cardiff, United Kingdom

Cumberland Infirmary

🇬🇧

Carlisle, United Kingdom

Queen Elizabeth Hospital

🇬🇧

Gateshead, United Kingdom

The New Victoria Hospital

🇬🇧

Glasgow, United Kingdom

Hinchingbrooke Hospital

🇬🇧

Huntingdon, United Kingdom

Royal Lancaster Infirmary

🇬🇧

Lancaster, United Kingdom

Luton & Dunstable Hospital

🇬🇧

Luton, United Kingdom

Queen Alexandra Hospital

🇬🇧

Portsmouth, United Kingdom

Royal Berkshire Hospital

🇬🇧

Reading, United Kingdom

East Surrey Hospital

🇬🇧

Redhill, United Kingdom

Queen's Hospital

🇬🇧

Romford, United Kingdom

Weston Park Hospital

🇬🇧

Sheffield, United Kingdom

Lister Hospital

🇬🇧

Stevenage, United Kingdom

Royal Marsden

🇬🇧

Sutton, United Kingdom

Basildon Hospital

🇬🇧

Basildon, United Kingdom

William Harvey Hospital

🇬🇧

Ashford, United Kingdom

Royal Sussex County Hospital

🇬🇧

Brighton, United Kingdom

Beaumont Hospital

🇮🇪

Dublin, Ireland

Stoke Mandeville Hospital

🇬🇧

Aylesbury, United Kingdom

Victoria Hospital

🇬🇧

Blackpool, United Kingdom

Pilgrim Hospital

🇬🇧

Boston, United Kingdom

Tallaght University Hospital

🇮🇪

Dublin, Ireland

Ysbyty Gwynedd

🇬🇧

Bangor, United Kingdom

Kidderminster General Hospital

🇬🇧

Kidderminster, United Kingdom

St George's Hospital

🇬🇧

London, United Kingdom

Singleton Hospital

🇬🇧

Swansea, United Kingdom

Royal Oldham Hospital

🇬🇧

Oldham, United Kingdom

Alexandra Hospital

🇬🇧

Redditch, United Kingdom

Salisbury District Hospital

🇬🇧

Salisbury, United Kingdom

Royal Albert Edward Infirmary

🇬🇧

Wigan, United Kingdom

Glan Clwyd Hospital

🇬🇧

Bodelwyddan, United Kingdom

North Devon District Hospital

🇬🇧

Barnstaple, United Kingdom

Kent and Canterbury Hospital

🇬🇧

Canterbury, United Kingdom

University Hospital Coventry and Warwickshire

🇬🇧

Coventry, United Kingdom

University Hospital of Wales

🇬🇧

Cardiff, United Kingdom

Cheltenham General Hospital

🇬🇧

Cheltenham, United Kingdom

Western General Hospital

🇬🇧

Edinburgh, United Kingdom

Darlington Memorial Hospital

🇬🇧

Darlington, United Kingdom

Darent Valley Hospital

🇬🇧

Dartford, United Kingdom

North Middlesex Hospital

🇬🇧

Edmonton, United Kingdom

Royal Devon and Exeter Hospital

🇬🇧

Exeter, United Kingdom

Princess Alexandra Hospital

🇬🇧

Harlow, United Kingdom

Northwick Park Hospital

🇬🇧

Harrow, United Kingdom

Inverclyde Royal Hospital,

🇬🇧

Greenock, United Kingdom

Wycombe Hospital

🇬🇧

High Wycombe, United Kingdom

Raigmore Hospital

🇬🇧

Inverness, United Kingdom

Kingston Hospital

🇬🇧

Kingston, United Kingdom

Airedale General Hospital

🇬🇧

Keighley, United Kingdom

Ipswich Hospital

🇬🇧

Ipswich, United Kingdom

Royal Marsden Hospital

🇬🇧

London, United Kingdom

Lincoln County Hospital

🇬🇧

Lincoln, United Kingdom

Queen Elizabeth The Queen Mother Hospital

🇬🇧

Margate, United Kingdom

North Manchester General Hospital

🇬🇧

Manchester, United Kingdom

Maidstone Hospital

🇬🇧

Maidstone, United Kingdom

Friarage Hospital

🇬🇧

Northallerton, United Kingdom

Wythenshawe Hospital,

🇬🇧

Manchester, United Kingdom

Milton Keynes University Hospital

🇬🇧

Milton Keynes, United Kingdom

Northampton General Hospital

🇬🇧

Northampton, United Kingdom

George Eliot Hospital

🇬🇧

Nuneaton, United Kingdom

Royal Alexandra Hospital

🇬🇧

Paisley, United Kingdom

King's Mill Hospital

🇬🇧

Sutton-in-Ashfield, United Kingdom

Royal Cornwall Hospital

🇬🇧

Truro, United Kingdom

Weston General Hospital

🇬🇧

Weston Super Mare, United Kingdom

West Cumberland Hospital

🇬🇧

Whitehaven, United Kingdom

Great Western Hospital

🇬🇧

Swindon, United Kingdom

Worcestershire Royal Hospital

🇬🇧

Worcester, United Kingdom

Wrexham Maelor Hospital

🇬🇧

Wrexham, United Kingdom

Cork University Hospital

🇮🇪

Cork, Ireland

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