European Celecoxib Trial in Primary Breast Cancer
This trial is active, not recruiting.
|Sponsor||Imperial College London|
|Collaborator||Institute of Cancer Research, United Kingdom|
|Start date||December 2005|
|End date||November 2017|
|Trial size||2639 participants|
|Trial identifier||NCT02429427, C/20/01|
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.
|Intervention model||parallel assignment|
|Masking||double blind (subject, caregiver, investigator)|
Disease free survival (DFS) benefit of two years adjuvant therapy with the COX-2 inhibitor celecoxib compared with placebo in primary breast cancer patients.
time frame: Patients will be assessed at baseline, months 3, 6 and 12 in the first year; at 6 monthly intervals in years 2 and 3; annually thereafter for years 4 to 10.
time frame: Date of randomisation until the date of death from any cause or censored at the date the patient was last seen alive. Assessed at baseline, months 3, 6 and 12 in the first year; at 6 monthly intervals in years 2 and 3; annually thereafter
Safety of adjuvant therapy with celecoxib in this patient population as assessed by the collection of adverse events according to the Common Terminology Criteria for Adverse Events
time frame: From randomisation until 30 days after completion of treament with celecoxib/placebo. Patients will be assessed at baseline, months 3, 6 and 12 in the first year; at 6 monthly intervals in year 2.
To compare incidence of second primary breast cancers
time frame: From randomisation until a second primary breast cancer is diagnosed. Patients will be assessed at baseline, months 3, 6 and 12 in the first year; at 6 monthly intervals in years 2 and 3; annually thereafter.
time frame: Cardiovascular assessments are carried out at the 12 month and 24 month time-points after randomisation. A cardiovascular assessment will also be carried out if treatment is stopped early (before the 24 month time-point).
Female participants at least 18 years old.
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
|Official title||A Phase III Multicentre Double Blind Randomised Trial of Celecoxib Versus Placebo in Primary Breast Cancer Patients|
|Principal investigator||Charles R Coombes, MD|
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