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

Phase 3
Conditions
Cancer
Registration Number
ISRCTN74358648
Lead Sponsor
niversity College London
Brief Summary

2019 Other publications in https://pubmed.ncbi.nlm.nih.gov/31477558/ feasibility analysis (added 02/06/2020) 2019 Abstract results in http://dx.doi.org/10.1200/JCO.2019.37.15_suppl.TPS3624 (added 14/11/2022)

Detailed Description

Not available

Recruitment & Eligibility

Status
Ongoing
Sex
All
Target Recruitment
11000
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 du

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

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Overall survival
Secondary Outcome Measures
NameTimeMethod
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
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