European Celecoxib Trial in Primary Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Celecoxib; Placebo
Intervention description: Patients will receive 400mg of Celecoxib once daily for two years or until disease progression (if before the two years limit) or until development of unacceptable toxicities. In addition ER(+) patients will receive endocrine treatment according to local practice.; Two capsules once daily with food
Intervention MeSH terms: Celecoxib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 2639.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Primary Breast Cancer; Celecoxib

Summary:

      It has been found that the chemical changes that take place in a patient's body during the
      development of inflammation may provide an environment which stimulates cancer cells. One
      step in the development of inflammation is the production of certain chemical substances
      which are important in the formation and spread of tumours. These are called prostaglandins.
      Cyclo-oxygenase II (COX-2) is an enzyme (a substance that speeds up chemical changes in the
      body) involved in the production of these prostaglandins and although it is not usually
      present in most tissues it is made at the sites of inflammation. Celecoxib is a selective
      Non-Steroidal Anti Inflammatory Drug (NSAID) which works by blocking the action of the COX-2
      enzyme, leading to a decrease in the production of prostaglandins and a reduction in
      inflammation.

      The purpose of this study is therefore to find out if celecoxib can be used after breast
      cancer treatment (chemotherapy and/ or radiotherapy) to reduce inflammation and thus reduce
      the ability of new tumours to grow and survive.

      2590 women with primary breast cancer will be recruited in this study from several locations
      in the United Kingdom and Germany. Eligible patients will be randomly allocated a treatment
      group, which can be celecoxib or placebo. Both treatments are taken orally (celecoxib 400mg
      daily, placebo 2 tablets daily) for a total of 2 years. In addition, hormone receptor
      positive patients will receive endocrine treatment as per local practice. Patients will
      prematurely discontinue treatment with celecoxib/placebo if disease progression is confirmed
      or if patients experience unacceptable toxicity.

      Patients will be seen every 6 months for the first 3 years and then off treatment follow-up
      is carried out annually. Participating patients will also be given the option to take part in
      the pathology sub-study by donating a sample of the tumour tissue collected at the time of
      the primary surgery.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Completely resected (greater or equal 1mm), histologically or cytologically proven
             unilateral breast cancer

          2. Female greater or equal 18 years of age

          3. If (neo) adjuvant chemotherapy received, patient must have received at least 4 cycles.
             Chemotherapy must be completed prior to study entry

          4. Hormone Receptor negatives must have received prior chemotherapy

          5. Study entry must be within any of the following timelines: 3 months of the end of
             definitive breast surgery OR between 3 weeks and 4 months after day 1 of the last
             cycle of adjuvant chemotherapy OR 6 weeks of the end of radiotherapy.

          6. WHO performance status 0 or 1

          7. Pre-treatment haematology and biochemistry values within acceptable local limits:
             Haemoglobin, white blood cell greater or equal to 3.0 x 109/l or absolute neutrophil
             count greater or equal to 1.51 x 109/l, Platelets greater or equal to 100 x 109/l,
             Serum bilirubin less than 1.5 x upper normal limit , Alkaline phosphatase less or
             equal to 1.5 x upper normal limit , Serum creatinine less than 1.5 x upper normal
             limit

          8. Negative pregnancy test for patients with child-bearing potential

          9. Normal baseline ECG and clinical cardiovascular assessment after completion of all
             (neo) adjuvant chemotherapy

         10. No previous or current evidence for metastatic disease

         11. Be accessible for and consent to long term follow-up

         12. Written informed consent prior to commencement of specific protocol procedures must be
             obtained and documented according to the local regulatory requirements

        Exclusion Criteria

          1. Patients with node negative, T1, Grade 1 breast cancer

          2. Unresectable, metastatic or bilateral breast cancer

          3. Active or previous peptic ulceration or gastrointestinal bleeding in the last year

          4. Active or previous history of inflammatory bowel disease

          5. A past history of adverse reaction/hypersensitivity to NSAIDs, including celecoxib and
             salicylates, or sulphonamides

          6. On current or planned chronic NSAIDs therapy (except low dose aspirin 100 mg four
             times per day or 325mg once daily).

          7. Current or long-term use of oral corticosteroids

          8. Known or suspected congestive heart failure (greater than New York Heart Association
             I) and/or coronary heart disease, previous history of myocardial infarction,
             uncontrolled arterial hypertension (ie BP greater than 160/90mmHg) under treatment
             with two anti-hypertensive drugs, rhythm abnormalities requiring permanent treatment.

          9. Patients with diabetes controlled by diet and oral medication are eligible for the
             study however patients with insulin dependent diabetes are excluded

         10. Past history of stroke/Transient ischaemic attack, symptomatic peripheral vascular
             disease or carotid disease

         11. Previously entered into an adjuvant chemotherapy trial for which approval for entry
             into REACT has not been granted

         12. ER receptor status unknown, Human epidermal growth factor receptor 2 or FISH positive,
             or Human epidermal growth factor receptor 2 status unknown

        14. Hormone Receptor negative and not received (neo)adjuvant chemotherapy 15. Use of
        hormone replacement therapy within the last 6 weeks 16. Pregnant or lactating women or
        women of childbearing potential unwilling/unable to use non-hormonal contraception 17. No
        previous or concomitant malignancies except adequately treated squamous cell / basal cell
        carcinoma of the skin, in situ carcinoma of the cervix or ductal carcinoma in situ/lobular
        carcinoma in situ of the breast, unless there has been a disease-free interval of 10 years
        or more 18. Psychiatric or addictive disorders which could preclude obtaining informed
        consent 19. Clinical evidence of severe osteoporosis and/or history of osteoporotic
        fracture