Add-Aspirin: the effects of aspirin on disease recurrence and survival after primary therapy in common non-metastatic solid tumours.

ISRCTN	ISRCTN74358648
DOI	https://doi.org/10.1186/ISRCTN74358648
EudraCT/CTIS number	2013-004398-28
IRAS number	120104
ClinicalTrials.gov number	NCT02804815
Secondary identifying numbers	18067, IRAS 120104

Submission date: 21/01/2015
Registration date: 21/01/2015
Last edited: 27/09/2024

Recruitment status: Recruiting
Overall study status: Ongoing
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-whether-aspirin-can-stop-cancer-coming-back-after-treatment-add-aspirin

Study website

Contact information

Ms Olawale Tijani
Public

MRC Clinical Trials Unit at UCL
90 High Holborn, 2nd floor
London
WC1V 6LJ
United Kingdom

Phone	+44 (0)207 670 4892
Email	mrcctu.add-aspirin@ucl.ac.uk

Study information

Study design	Randomized; Interventional
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use contact details to request a patient information sheet
Scientific title	A phase III double-blind placebo-controlled randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common non-metastatic solid tumours.
Study hypothesis	Aim: To assess whether regular aspirin use after standard cancer therapy prevents recurrence and prolongs survival in patients with early stage common solid tumours. International recruitment will allow assessment of the intervention in different communities.
Ethics approval(s)	14/SC/0171; First MREC approval date 04/06/2014
Condition	Cancer
Intervention	1. Randomised blinded phase: Participants will be randomly assigned to 100 mg aspirin, 300 mg aspirin or matched placebo. All tablets will be enteric-coated to be taken daily for at least five years 2. Run-in feasibility phase: During the feasibility phase of the study, all participants will take open label 100 mg aspirin daily for a run-in period of approximately 8 weeks prior to randomisation
Intervention type	Other
Primary outcome measure	Overall survival
Secondary outcome measures	Added 07/12/2023: 1. Adherence, toxicity including serious haemorrhage, and cardiovascular events, recorded on the study-specific CRFs at each visit. Participants are asked how often they took their tablets at every visit and if they have experienced new or worsening symptoms; the CRF also lists aspirin-related toxicities which are asked about and graded by the clinician. 2. Tumour-specific items such as scan (eg. CT) and tests (e.g. prostate-specific antigen (PSA) are recorded at each study visit once study treatment has started
Overall study start date	01/03/2015
Overall study end date	31/10/2026

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	16 Years
Sex	Both
Target number of participants	Planned Sample Size: 11000; UK Sample Size: 9189
Participant inclusion criteria	Common inclusion criteria: 1. Written informed consent 2. WHO performance status 0, 1 or 2 3. Previous or current participants of other primary treatment trials if agreed in advance between trials 4. No clinical or radiological evidence of residual or distant disease Breast cohort inclusion criteria: 1. Men or women with histologically confirmed invasive breast cancer 2. Undergone complete primary invasive tumour excision with clear margins 3. Surgical staging of the axilla must have been undertaken by sentinel node biopsy, axillary sampling or dissection 4. In those patients with a positive sentinel node biopsy: 4.1. If 1, 2 or 3 nodes are positive, subsequent management of the axilla (with surgery, radiotherapy or no further intervention) should be completed prior to registration 4.2. If 4 or more nodes are involved, patients must have undergone completion axillary node dissection 5. Radiotherapy (RT): 5.1. Patients who have undergone breast-conserving surgery should receive adjuvant RT 5.2. Patients who have undergone mastectomy should receive RT if they have more than 3 axillary lymph nodes involved 5.3. Patients who have undergone mastectomy and have T3 tumours and/or 1, 2 or 3 involved lymph nodes may (or not) receive radiation per institutional practice 6. Final histology must fall within at least one of these 3 groups: 6.1. Node positive 6.2. Node negative with high-risk features 2 or more of: 6.2.1. ER negative 6.2.2. HER2 positive 6.2.3. Grade 3 6.2.4. Lymphovascular invasion present 6.2.5. Age <35 6.2.6. Oncotype Dx score of >25 6.3. In patients who have received neoadjuvant chemotherapy, patients are eligible if they have both a hormone receptor negative/HER2 negative tumour, a HER2 positive tumour or a hormone receptor positive grade 3 tumour and did not achieve a pathological complete response with neoadjuvant systemic therapy 7. Patients who received standard neoadjuvant and/or adjuvant chemotherapy or RT are eligible 8. Known HER2 and ER status 9. Participants may receive endocrine therapy and trastuzumab. All ER-positive patients should be planned to undergo at least 5 years of adjuvant endocrine therapy Colorectal cohort inclusion criteria: 1. Histologically confirmed stage II or III adenocarcinoma of the colon or rectum and patients who have undergone resection of liver metastases with clear margins and no residual metastatic disease 2. Patients with synchronous tumours if one of the tumours is at least stage II or III 3. Serum CEA ideally =1.5 x upper limit of normal 4. Have undergone curative (R0) resection with clear margins Gastroesophageal cohort inclusion criteria: 1. Patients with histologically confirmed adenocarcinoma, adenosquamous carcinoma or squamous cell cancer of the oesophagus, gastroesophageal junction or stomach 2. Have undergone curative (R0) resection with clear margins or primary chemoRT given with curative intent Prostate cohort inclusion criteria: 1. Men with histologically confirmed node negative nonmetastatic adenocarcinoma of the prostate 2. Have undergone curative treatment, either: 2.1. Radical prostatectomy 2.2. Radical RT 2.3. Salvage RT (following rise in PSA after prostatectomy) 3. Intermediate or high risk according to D’Amico classification Treatment pathway-specific inclusion criteria: 1. Prostatectomy patients: 1.2. Open, laparoscopic or robotic radical prostatectomy 1.3. Men treated with immediate adjuvant RT 1.4. Men receiving adjuvant hormone therapy planned for a maximum duration of 3 years 1.5. Men randomised to any of the 3 arms of RADICALS HD are eligible Prostatectomy patients 2. Radical RT patients: 2.1. Men receiving neoadjuvant and/or adjuvant hormone therapy planned for a maximum duration of 3 years 3. Salvage RT patients following PSA rise after previous radical prostatectomy: 3.1. Men treated with salvage RT following a rise in PSA are eligible 3.2. Men receiving neo and/or adjuvant hormone therapy planned for a maximum of 3 years 3.3. Men randomised to any of the 3 arms of RADICALS HD are eligible
Participant exclusion criteria	Participants must not meet any of the common or their tumour specific exclusion criteria. Common exclusion criteria: 1. Current or previous regular use of aspirin (at any dose) or current use of another NSAID for any indication 2. 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 3. Current use of anticoagulants 4. Current or longterm use of oral corticosteroids. The treating physician should make the clinical decision whether a patient has been exposed to longterm therapy 5. Active or previous peptic ulceration or gastrointestinal bleeding within the last year, except where the cause of bleeding has been surgically removed 7. Active or previous history of inflammatory bowel disease 8. History of moderate or severe renal impairment, with eGFR<45ml/min/1.73m2. 9. Previous invasive or noninvasive malignancy except: 9.1. DCIS where treatment consisted of resection alone. 9.2. Prostate cancer initially treated with prostatectomy and now being treated with salvage radiotherapy following a rise in PSA. 9.3. Cervical carcinoma in situ where treatment consisted of resection alone. 9.4. Basal cell carcinoma where treatment consisted of resection alone or radiotherapy. 9.5. Superficial bladder carcinoma where treatment consisted of resection alone. 9.6. Other cancers where the patient has been disease free for =15 years. 10. Any other physical condition which is associated with increased risk of aspirin related 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 11. Known glucose6phosphate dehydrogenase deficiency 12. Known lactose intolerance 13. LFTs greater than 1.5x the upper limit of normal unless agreed with TMG 14. Anticipated difficulties in complying with trial treatment or followup schedules 15. <16 years old 16. Participants in other treatment trials where this has not been agreed in advance by both trial teams 17. Pregnant or breast feeding, or intending to become pregnant or breast feed during the trial treatment period Breast cohort exclusion criteria: 1. Metastatic or bilateral breast cancer. Colorectal cohort exclusion criteria: 1. Proven (or clinically suspected) metastatic disease (patients who have undergone resection of liver metastases with clear margins and no residual metastatic disease are eligible) Gastroesophageal cohort exclusion criteria: 1. Proven (or clinically suspected) metastatic disease. Prostrate cohort participant criteria: 1. Biopsy proven or radiologically suspected nodal involvement, or distant metastases from prostate cancer 2. Adjuvant hormone therapy planned for >3 years 3. Bilateral orchidectomy
Recruitment start date	01/03/2015
Recruitment end date	01/06/2025

Locations

Countries of recruitment

England
India
Ireland
United Kingdom

Study participating centre

Medical Research Council Clinical Trials Unit (MRC CTU)

90 High Holborn
2nd Floor
London
WC1V 6LJ
United Kingdom

Sponsor information

University College London
University/education

Gower Street
London
WC1E 6BT
England
United Kingdom

"ROR"	https://ror.org/02jx3x895

Funders

Funder type

Government

National Institute for Health Research
Government organisation / National government

Alternative name(s): National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Location: United Kingdom

Cancer Research UK
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Results and Publications

Intention to publish date	31/12/2027
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Results from each of the four tumour-specific cohorts will be submitted (separately) for publication in high impact peer-reviewed journals; timelines differ for the different cohorts with expected dates for dissemination between June 2026 and December 2027.
IPD sharing plan	Access to data or samples will be via application to the Trial Steering Committee (TSC) and will be managed according to the standard policy and process in place at the MRC Clinical Trials Unit at UCL. Applicants will need to provide details of the data/samples being requested, the proposed study, funding and ethical approvals, and the credentials of the research group. Participants provide consent for future use of data and samples in ethically approved research studies.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Other publications	feasibility analysis	01/11/2019	02/06/2020	Yes	No
Abstract results		26/05/2019	14/11/2022	No	No
HRA research summary			28/06/2023	No	No

Editorial Notes

27/09/2024: Contact details updated.
07/12/2023: The following changes were made to the study record:
1. IRAS number, ClinicalTrials.gov number, secondary outcome measures, study website added.
2. The recruitment end date was changed from 28/02/2021 to 01/06/2025.
3. Study participating centre address and contact details updated.
4. Ireland and India were added to the countries of recruitment.
14/11/2022: Abstract added.
08/02/2021: The following changes have been made:
1. The publication and dissemination plan and IPD sharing statement have been added.
2. The intention to publish date has been added.
05/02/2021: The overall trial end date has been changed from 28/02/2021 to 31/10/2026.
11/06/2020: The public contacts have been added and the previous scientific contact removed.
02/06/2020: Publication reference added.