Add-Aspirin: A Trial Assessing the Effects of Aspirin on Disease Recurrence and Survival After Primary Therapy in Common Non Metastatic Solid Tumours
Oncology / Posted 1 year ago
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.
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.
@@ *For condition specific inclusion/exclusion criteria please follow the link below:*
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Inclusion Criteria :
- Ages Eligible for Study: 16 Years and older (Child, Adult, Older Adult)
- Sexes Eligible for Study: All
- Accepts Healthy Volunteers: No
- Written informed consent
- WHO performance status 0, 1 or 2
- Participants should not be and have no intention of pregnancy or breast feeding during trial treatment
- Previous or current participants of other primary treatment trials if agreed in advance between trials
- No clinical or radiological evidence of residual or distant disease
- Conditions eligible for this trial include:
- Breast cancers
- Prostate cancers
- Colorectal cancers
- Gastro-oesophageal cancers https://www.clinicaltrials.gov/ct2/show/NCT02804815?recrs=a&cond=%22Esophageal+Cancer%22&map_cntry=GB&draw=2#contacts
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Exclusion Criteria :
- Current or previous regular use of aspirin (at any dose) or current use of another NSAID for any indication.
- A past history of adverse reaction or hypersensitivity to NSAIDs, celecoxib, aspirin or other salicylates or sulphonamides, including asthma, that is exacerbated by use of NSAIDs.
- Current use of anticoagulants.
- Current or longterm use of oral corticosteroids. The treating physician should make the clinical decision whether a patient has been exposed to longterm therapy.
- Active or previous peptic ulceration
- Previous gastrointestinal bleeding except where the cause of the bleeding has been surgically removed.
- Active or previous history of inflammatory bowel disease.
- History of moderate or severe renal impairment, with eGFR<45ml/min/1.73m2.
- Previous invasive or noninvasive malignancy except:
- - DCIS where treatment consisted of resection alone. Prostate cancer initially treated with prostatectomy and now being treated with salvage radiotherapy following a rise in PSA.
- - Cervical carcinoma in situ where treatment consisted of resection alone.
- Basal cell carcinoma where treatment consisted of resection alone or radiotherapy.
- Superficial bladder carcinoma where treatment consisted of resection alone.
- Other cancers where the patient has been diseasefree for ≥15 years.
- Any other physical condition which is associated with increased risk of aspirinrelated morbidity or, in the opinion of the Investigator, makes the patient unsuitable for the trial, including but not limited to severe asthma, haemophilia and other bleeding diatheses, macular degeneration and patients with a high risk of mortality from another cause within the trial treatment period.
- Known glucose6phosphate dehydrogenase deficiency.
- LFTs greater than 1.5x the upper limit of normal unless agreed with TMG.
- Anticipated difficulties in complying with trial treatment or follow-up schedules.
- <16 years old.
- Participants in other treatment trials where this has not been agreed in advance by both trial teams.
- BREAST COHORT EXCLUSION CRITERIA
- • Metastatic or bilateral breast cancer.
- COLORECTAL COHORT EXCLUSION CRITERIA
- • Proven (or clinically suspected) metastatic disease (patients who have undergone resection of liver metastases with clear margins and no residual metastatic disease are eligible).
- GASTROOESOPHAGEAL COHORT EXCLUSION CRITERIA
- • Proven (or clinically suspected) metastatic disease.
- PROSTATE COHORT EXCLUSION CRITERIA
- Biopsy proven or radiologically suspected nodal involvement, or distant metastases from prostate cancer.
- Adjuvant hormone therapy planned for >3 years.
- Study start date : October 2015
- Study end date : October 2026
- Wales-Based Study Contact : Please speak to your clinician
- Principal Investigator : Ruth Langley (MRC CTU at UCL)