Eligibility

Providing potential participants with trial information (see Participant Information Sheet) at the earliest opportunity following or during their primary therapy will allow time for them to consider their participation and for any queries or issues surrounding eligibility to be addressed. Participants should be registered for the run-in period as soon as it is considered clinically safe to do so (see diagrams showing timing of trial entry for each cohort). After the run-in period, participants should be assessed to ensure suitability for the study prior to randomisation.

There will be no exceptions to eligibility requirements at the time of registration and randomisation.

Participants will be considered eligible for enrolment if they fulfil all the inclusion criteria and none of the exclusion criteria as defined in the following sections. Eligibility should be assessed at registration and those not meeting the criteria should not join the study. After the run-in period, participants will be assessed to ensure suitability for the study prior to randomisation.

For any eligibility queries, please contact the Trial Managers at the MRC CTU (mrcctu.add-aspirin@ucl.ac.uk) prior to attempting to register or randomise the participant.

Please select relevant cohort for detailed eligibility criteria  

BREAST COHORT EXCLUSION CRITERIA
  1. Metastatic or bilateral breast cancer.
  2. Current or previous regular use of aspirin (at any dose) or current use of another NSAID for any indication (see appendix IV for list of medications not permitted in the trial).
    1. Regular aspirin use is defined as taking aspirin more than twice in any given week for more than 4 consecutive weeks.
    2. Current NSAID use is defined as taking any NSAID for more than a week in the preceding month. If investigators feel that this definition may unfairly exclude a participant, this can be discussed with the MRC CTU and a case by case decision will be made.
  3. 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.
  4. Current use of anti-coagulants.
  5. Current or long-term use of oral corticosteroids. The treating physician should make the clinical decision whether a patient has been exposed to long-term therapy.
  6. Active or previous peptic ulceration or gastrointestinal bleeding within the last year, except where the cause of the 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 non-invasive malignancy except:
    1. DCIS where treatment consisted of resection alone.
    2. Cervical carcinoma in situ where treatment consisted of resection alone.
    3. Basal cell carcinoma where treatment consisted of resection alone or radiotherapy.
    4. Superficial bladder carcinoma where treatment consisted of resection alone.
    5. 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 glucose-6-phosphate dehydrogenase (G6PD) deficiency.
  12. Known lactose intolerance.
  13. LFTs greater than 1.5x the upper limit of normal unless the participant has been discussed with the MRC CTU and the Trial Management Group (TMG) agrees that they are suitable for the trial. This will be decided on a case-by-case basis.
  14. Anticipated difficulties in complying with trial treatment or follow-up schedules.
  15. <16 years old in the UK or <18 years old in India.
  16. Participants in other treatment trials where this has not been agreed in advance by both trial teams. Specific trials where a second randomisation has already been agreed with the relevant trial teams are indicated in section 4.4.1 of the protocol. For all other trials, this should be discussed with the Trial Managers at the MRC CTU in the first instance.
  17. Pregnant or breast feeding, or intending to become pregnant or breast feed during the trial treatment period. Participants should agree to inform the trial team if they subsequently become pregnant, or plan to become pregnant, whilst they are still receiving treatment in the trial (see section 5.4.4 of the protocol).
BREAST COHORT INCLUSION CRITERIA
  1. Men or women with histologically confirmed invasive breast cancer.
  2. Patients have undergone complete primary invasive tumour excision with clear margins as judged by the multidisciplinary team.
  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:
    1. If 1, 2 or 3 nodes are positive, subsequent management of the axilla (with surgery, radiotherapy or no further intervention) should follow institutional policy, and be completed prior to registration.
    2. If 4 or more nodes are involved, patients must have undergone completion axillary node dissection.
  5. Radiotherapy:
    1. Patients who have undergone breast-conserving surgery should receive adjuvant radiotherapy.
    2. Patients who have undergone mastectomy should receive radiotherapy if they have more than 3 axillary lymph nodes involved.
    3. Patients who have undergone mastectomy and have T3 tumours and/or 1, 2 or 3 involved lymph nodes may (or not) receive radiation as per institutional practice.
  6. Final histology must fall within at least one of these three groups:
    1. Node positive
    2. Node negative with high-risk features, defined as two or more of:
      1. ER negative (Allred score <3/8 or negative according to institutional criteria)
      2. HER2 positive
      3. Grade 3
      4. Lymphovascular invasion present
      5. Age less than 35
      6. Oncotype Dx score of >25
      7. In the above definitions patients with micrometastases should be regarded as node positive. Patients with isolated tumour cells should be regarded as node negative.
    3. Patients who have received neo-adjuvant chemotherapy and have both:
      1. A hormone receptor negative/HER2 negative tumour, a HER2 positive tumour or a hormone receptor positive grade 3 tumour, and,
      2. Did not achieve a pathological complete response with neoadjuvant systemic therapy (defined as no invasive cancer on H&E evaluation of the resected breast specimen and all sampled ipsilateral axillary lymph nodes).
  7. Patients who received standard neo-adjuvant and/or adjuvant chemotherapy or radiotherapy are eligible. Timing of trial registration in terms of the treatment pathway should be as described in section 4.2 of the protocol . (For confirmation of standard therapy, please contact MRC CTU).
  8. Known HER2 and ER status.
  9. No clinical or radiological evidence of residual or distant disease according to routine practice staging tests.
  10. Participants may receive endocrine therapy and trastuzumab according to standard practice concomitant with trial participation. All participants with ER positive disease should be planned to undergo a minimum of 5 years of adjuvant endocrine therapy using standard agents or as part of an agreed trial.
  11. Patients who are already participating (or have participated) in other primary treatment trials may be eligible but this must be agreed in advance with the relevant trial teams. Trials where there is already an agreement in place are listed in section 4.4.1 of the protocol. If a potential participant is enrolled in a trial that is not listed, this should be discussed with the MRC CTU prior to registration.
  12. WHO performance status 0, 1 or 2.
  13. Written informed consent.
COLON/RECTUM COHORT INCLUSION CRITERIA
  1. Histologically confirmed stage II or stage III (see appendix VII) 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 (ULN). Participants outside of this range can be discussed with the MRC CTU on an individual basis.
  4. Have undergone curative (R0) resection with clear margins (margins ≥1mm or as judged by the multidisciplinary team).
  5. Patients who have received standard neo-adjuvant and/or adjuvant treatment or therapy within an agreed trial. Timing of trial registration in terms of the treatment pathway should be as described in section 4.2 of the protocol. (For confirmation of standard therapy, please contact MRC CTU).
  6. No clinical or radiological evidence of residual or distant disease according to routine practice staging tests.
  7. Patients with known Lynch Syndrome are eligible, however CAPP3 trial should be offered in preference to Add-Aspirin if available. Patients that are not eligible for CAPP3 and patients that decline CAPP3 can be offered Add-Aspirin.
  8. Patients who are already participating (or have participated) in other primary treatment trials may be eligible but this must be agreed in advance with the relevant trial teams. Trials where there is already an agreement in place are listed below in section 4.4.2 of the protocol. If a potential participant is enrolled in a trial that is not listed, this should be discussed with the MRC CTU prior to registration.
  9. WHO performance status 0, 1 or 2.
  10. Written informed consent.
COLON/RECTUM 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).
  2. Current or previous regular use of aspirin (at any dose) or current use of another NSAID for any indication (see appendix IV for list of medications not permitted in the trial).
    1. Regular aspirin use is defined as taking aspirin more than twice in any given week for more than 4 consecutive weeks.
    2. Current NSAID use is defined as taking any NSAID for more than a week in the preceding month. If investigators feel that this definition may unfairly exclude a participant, this can be discussed with the MRC CTU and a case by case decision will be made.
  3. A past history of adverse reaction/hypersensitivity to NSAIDs, celecoxib, aspirin or other salicylates or sulphonamides, including asthma that is exacerbated by use of NSAIDs.
  4. Current use of anti-coagulants.
  5. Current or long-term use of oral corticosteroids. The treating physician should make the clinical decision whether a patient has been exposed to long-term therapy.
  6. Active or previous peptic ulceration or gastrointestinal bleeding within the last year, except where the cause of the 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 non-invasive malignancy except:
    1. DCIS where treatment consisted of resection alone.
    2. Cervical carcinoma in situ where treatment consisted of resection alone.
    3. Basal cell carcinoma where treatment consisted of resection alone or radiotherapy.
    4. Superficial bladder carcinoma where treatment consisted of resection alone.
    5. 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 G6PD deficiency.
  12. Known lactose intolerance.
  13. LFTs greater than 1.5x the upper limit of normal unless the participant has been discussed with the MRC CTU and the TMG agrees that they are suitable for the trial. This will be decided on a case-by-case basis.
  14. Anticipated difficulties in complying with trial treatment or follow-up schedules.
  15. <16 years old in the UK or <18 years old in India.
  16. Participants in other treatment trials where this has not been agreed in advance by both trial teams. Specific trials where a second randomisation has already been agreed with the relevant trial teams are indicated in section 4.4.2 of the protocol. For all other trials, this should be discussed with the Trial Managers at the MRC CTU in the first instance.
  17. Pregnant or breast feeding, or intending to become pregnant or breast feed during the trial treatment period. Participants should agree to inform the trial team if they subsequently become pregnant, or plan to become pregnant, whilst they are still receiving treatment in the trial (see section 5.4.4 of the protocol).
STOMACH/OESOPHAGUS COHORT INCLUSION CRITERIA
  1. Patients with histologically confirmed adenocarcinoma, adenosquamous carcinoma or squamous cell cancer of the oesophagus, gastro-oesophageal junction or stomach.
  2. Have undergone curative (R0) resection with clear margins (margin ≥1mm or as judged by the multidisciplinary team) or primary chemoradiotherapy given with curative intent.
  3. Patients who have received standard neo-adjuvant and/or adjuvant treatment or therapy within an agreed trial are eligible. Timing of trial registration in terms of the treatment pathway should be as described in section 4.2 of the protocol. (For confirmation of standard therapy, please contact MRC CTU).
  4. No clinical or radiological evidence of residual or distant disease according to routine practice staging tests.
  5. Those who have undergone a partial gastrectomy or oesophagectomy should be prescribed a proton pump inhibitor for the duration of the trial where no contraindication exists.
  6. Patients who are already participating (or have participated) in other primary treatment trials may be eligible but this must be agreed in advance with the relevant trial teams. Trials where there is already an agreement in place are listed in section 4.4.3 of the protocol. If a potential participant is enrolled in a trial that is not listed, this should be discussed with the MRC CTU prior to registration.
  7. WHO performance status 0, 1 or 2.
  8. Written informed consent.
STOMACH-OESOPHAGUS COHORT EXCLUSION CRITERIA
  1. Proven (or clinically suspected) metastatic disease.
  2. Current or previous regular use of aspirin (at any dose) or current use of another NSAID for any indication (see appendix IV for list of medications not permitted in the trial).
    1. Regular aspirin use is defined as taking aspirin more than twice in any given week for more than 4 consecutive weeks.
    2. Current NSAID use is defined as taking any NSAID for more than a week in the preceding month. If investigators feel that this definition may unfairly exclude a participant, this can be discussed with the MRC CTU and a case by case decision will be made.
  3. A past history of adverse reaction/hypersensitivity to NSAIDs, celecoxib, aspirin or other salicylates or sulphonamides, including asthma that is exacerbated by use of NSAIDs.
  4. Current use of anti-coagulants.
  5. Current or long-term use of oral corticosteroids. The treating physician should make the clinical decision whether a patient has been exposed to long-term therapy.
  6. Active or previous peptic ulceration or gastrointestinal bleeding within the last year, except where the cause of the 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 non-invasive malignancy except:
    1. DCIS where treatment consisted of resection alone.
    2. Cervical carcinoma in situ where treatment consisted of resection alone.
    3. Basal cell carcinoma where treatment consisted of resection alone or radiotherapy.
    4. Superficial bladder carcinoma where treatment consisted of resection alone.
    5. 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 G6PD deficiency.
  12. Known lactose intolerance.
  13. LFTs greater than 1.5x the upper limit of normal unless the participant has been discussed with the MRC CTU and the TMG agrees that they are suitable for the trial. This will be decided on a case-by-case basis.
  14. Anticipated difficulties in complying with trial treatment or follow-up schedules.
  15. <16 years old in the UK or <18 years old in India.
  16. Participants in other treatment trials where this has not been agreed in advance by both trial teams. Specific trials where a second randomisation has already been agreed with the relevant trial teams are indicated in section 4.4.3 of the protocol. For all other trials, this should be discussed with the Trial Managers at the MRC CTU in the first instance.
  17. Pregnant or breast feeding, or intending to become pregnant or breast feed during the trial treatment period. Participants should agree to inform the trial team if they subsequently become pregnant, or plan to become pregnant, whilst they are still receiving treatment in the trial (see section 5.4.4 of the protocol).
PROSTATE COHORT INCLUSION CRITERIA
  1. Men with histologically confirmed, node negative, non-metastatic adenocarcinoma of the prostate (T1-3a, N0). See appendix X for TNM staging definitions.
  2. Have undergone curative treatment, either
    1. Radical prostatectomy.
    2. Radical radiotherapy (external beam or brachytherapy).
    3. Salvage radiotherapy following a rise in PSA after radical prostatectomy.
  3. Intermediate or high risk according to D’Amico classification76 (prior to radical treatment, see table below).

    D’Amico Classification

    Risk classification

     

    Low

    § PSA less than or equal to 10

    § And Gleason score less than or equal to 6

    § Or clinical stage T1-2a

    Intermediate

    § PSA between 10 and 20

    § Or Gleason score of 7

    § Or clinical stage T2b

    High

    § PSA more than 20

    § Or Gleason score equal or larger than 8

    § Or clinical stage T2c-3a

  4. WHO performance status 0, 1 or 2.
  5. Written informed consent.
    Depending on the curative treatment pathway, participants must additionally satisfy the following:
    (a) Prostatectomy patients
  6. Open, laparoscopic or robotic radical prostatectomy.
  7. Men treated with immediate adjuvant radiotherapy are eligible. Timing of trial registration in terms of the treatment pathway should be as described in section 4.2 of the protocol.
  8. Men receiving adjuvant hormone therapy (LHRH agonists, LHRH antagonists, bicalutamide monotherapy), planned for a maximum duration of three years, are eligible. Treatment can be ongoing at the time of registration/randomisation to Add-Aspirin.
  9. Men randomised to any of the 3 arms of RADICALS Hormone Duration study (RADICALS-HD, ISRCTN 40814031) are eligible provided all other eligibility criteria are met.
    (b) Radical radiotherapy patients.
  10. Men receiving neo-adjuvant and/or adjuvant hormone therapy (LHRH agonists, LHRH antagonists, bicalutamide monotherapy) planned for a maximum duration of three years are eligible, and this treatment may be ongoing at the time of registration in Add-Aspirin.
  11. Timing of registration in Add-Aspirin in terms of the treatment pathway should be as described in section 4.2 of the protocol.
    (c) Salvage radiotherapy patients (following rise in PSA after previous radical prostatectomy)
  12. Men treated with salvage radiotherapy following a rise in PSA are eligible. Timing of trial registration in terms of the treatment pathway should be as described in section 4.2 of the protocol.
  13. Men receiving neo-adjuvant and/or adjuvant hormone therapy (LHRH agonists, LHRH antagonists, bicalutamide monotherapy) planned for a maximum duration of three years are eligible, and this treatment may be ongoing at the time of registration in Add-Aspirin.
  14. Men randomised to any of the 3 arms of RADICALS Hormone Duration study (RADICALS-HD, ISRCTN 40814031) are eligible provided all other eligibility criteria are met.
PROSTATE COHORT EXCLUSION 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.
  4. Current or previous regular use of aspirin (at any dose) or current use of another NSAID for any indication (see appendix IV for list of medications not permitted in the trial).
    a. Regular aspirin use is defined as taking aspirin more than twice in any given week for more than 4 consecutive weeks.
    b. Current NSAID use is defined as taking any NSAID for more than a week in the preceding month. If investigators feel that this definition may unfairly exclude a participant, this can be discussed with the MRC CTU and a case by case decision will be made.
  5. A past history of adverse reaction/hypersensitivity to NSAIDs, celecoxib, aspirin or other salicylates or sulphonamides, including asthma that is exacerbated by use of NSAIDs.
  6. Current use of anti-coagulants.
  7. Current or long-term use of oral corticosteroids. The treating physician should make the clinical decision whether a patient has been exposed to long-term therapy. 
  8. Active or previous peptic ulceration or gastrointestinal bleeding, except where the cause of the bleeding has been surgically removed.
  9. Active or previous history of inflammatory bowel disease.
  10. History of moderate or severe renal impairment, with eGFR<45ml/min/1.73m2.
  11. Previous invasive or non-invasive malignancy except:
    a. Prostate cancer initially treated with prostatectomy and now being treated with salvage radiotherapy following a rise in PSA.
    b. Basal cell carcinoma where treatment consisted of resection alone or radiotherapy.
    c. Low grade superficial bladder carcinoma where treatment consisted of endoscopic resection alone.
    d. Other cancers where the patient has been disease-free for ≥15 years.
  12. 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.
  13. Known G6PD deficiency.
  14. Known lactose intolerance.
  15. LFTs greater than 1.5x the upper limit of normal unless the participant has been discussed with the MRC CTU and the TMG agrees that they are suitable for the trial. This will be decided on a case-by-case basis.
  16. Anticipated difficulties in complying with trial treatment or follow-up schedules.
  17. <16 years old in the UK or <18 years old in India.
  18. Participants in other treatment trials where this has not been agreed in advance by both trial teams. Specific trials where a second randomisation has already been agreed with the relevant trial teams are indicated in the inclusion criteria. For all other trials, this should be discussed with the Trial Managers at the MRC CTU in the first instance.

Contact Details

If you are an individual who is interested in taking part in Add-Aspirin, please talk to your doctor who will be able to consider whether you are suitable for the trial.

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For healthcare professionals

If your centre would like to recruit participants to Add-Aspirin, contact us:
mrcctu.add-aspirin@ucl.ac.uk

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