ELIGIBILITY CRITERIA - BREAST

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).
    • 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.
  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:
    • a. DCIS where treatment consisted of resection alone.
    • b. Cervical carcinoma in situ where treatment consisted of resection alone.
    • c. Basal cell carcinoma where treatment consisted of resection alone or radiotherapy.
    • d. Superficial bladder carcinoma where treatment consisted of resection alone.
    • e. 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:
    • a. 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.
    • b. If 4 or more nodes are involved, patients must have undergone completion axillary node dissection.
  5. Radiotherapy:
    • a. Patients who have undergone breast-conserving surgery should receive adjuvant radiotherapy.
    • b. Patients who have undergone mastectomy should receive radiotherapy if they have more than 3 axillary lymph nodes involved.
    • c. 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:
    • a. Node positive
    • b. Node negative with high-risk features, defined as two or more of:
      • i. ER negative (Allred score <3/8 or negative according to institutional criteria)
      • ii. HER2 positive
      • iii. Grade 3
      • iv. Lymphovascular invasion present
      • v. Age less than 35
      • vi. Oncotype Dx score of >25
      • vii. In the above definitions patients with micrometastases should be regarded as node positive. Patients with isolated tumour cells should be regarded as node negative.
    • c. Patients who have received neo-adjuvant chemotherapy and have both:
      • i. A hormone receptor negative/HER2 negative tumour, a HER2 positive tumour or a hormone receptor positive grade 3 tumour, and,
      • ii. 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.


The trial is being jointly funded by Cancer Research UK (grant number C471 /A15015, www.cancerresearchuk.org), the National Institute for Health Research Health Technology Assessment Programme (project number 12/01/38, www.nihr.ac.uk) and the MRC Clinical Trials Unit at UCL.
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