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European Celecoxib Trial in Primary Breast Cancer (REACT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02429427
Recruitment Status : Completed
First Posted : April 29, 2015
Results First Posted : June 23, 2020
Last Update Posted : June 23, 2020
Institute of Cancer Research, United Kingdom
Information provided by (Responsible Party):
Imperial College London

Brief 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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Celecoxib Other: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2639 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III Multicentre Double Blind Randomised Trial of Celecoxib Versus Placebo in Primary Breast Cancer Patients
Actual Study Start Date : December 2005
Actual Primary Completion Date : March 2019
Actual Study Completion Date : March 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Celecoxib

Arm Intervention/treatment
Experimental: Celecoxib
Patients in this arm will receive 400mg of celecoxib once daily. In addition, Hormone Receptor (+) patients will receive endocrine treatment according to local practice.
Drug: Celecoxib
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.
Other Name: Celebrex, Onsenal, Celebra

Placebo Comparator: Placebo
Patients in this arm will receive 2 tablets once daily. In addition Hormone Receptor (+) patients will receive endocrine treatment according to local practice.
Other: Placebo
Two capsules once daily with food

Primary Outcome Measures :
  1. 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 followed up to 10 years. DFS will be calculated from date of randomization until the date of first documented DFS event, this will be assessed at 2 and 5 years ]
    From time of randomisation to the date of first event; with events contributing to the analysis defined as loco-regional and distant breast cancer recurrence, new primary breast cancer (ipsilateral or contralateral) and death without disease relapse (intercurrent death)

Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: Date of randomisation until the date of death from any cause or censored at the date the patient was last seen alive, this will be assessed at 2 and 5 years ]
    First local recurrence and first distant recurrence will be recorded on separate parts of the CRF. In the event of local progression, all patients must be followed up for distant recurrence, second malignancy and survival. Similarly in the case of second malignancy, the appropriate CRF should be completed and patients should REACT Protocol, Version 39, dated 01.11.2016 Page 34 of 48 continue to be followed for disease progression and where possible the relation of any subsequent disease progression and/or death due to the primary or second cancer should be established.

  2. Number of Participants With Incidence of Second Primary Breast Cancers [ Time Frame: From randomisation until a second primary breast cancer is diagnosed. Patients will be followed up to 10 years. ]
    Any malignant contralateral breast disease will be included and recorded as a second primary

  3. Cardiovascular Mortality [ Time Frame: Patients are followed up to 10 years, any deaths within this timeframe with cardiovascular involvement reported are included in the analysis. ]
    Number of deaths recorded as having cardiovascular involvement are reported by treatment group.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02429427

Sponsors and Collaborators
Imperial College London
Institute of Cancer Research, United Kingdom
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Principal Investigator: Charles R Coombes, MD Imperial College London
  Study Documents (Full-Text)

Documents provided by Imperial College London:
Study Protocol  [PDF] November 1, 2016
Statistical Analysis Plan  [PDF] June 11, 2014

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT02429427    
Other Study ID Numbers: C/20/01
First Posted: April 29, 2015    Key Record Dates
Results First Posted: June 23, 2020
Last Update Posted: June 23, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Imperial College London:
Primary Breast Cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action