REACT (Randomised EuropeAn Celecoxib Trial)

A Phase III Multicentre Double Blind Randomised Trial of Celecoxib versus Placebo in Primary Breast Cancer Patients

Further information

ICCG/C/20/01, GBG 27, BIG 1-03

Acronym: REACT (Randomised EuropeAn Celecoxib Trial)
ISRCTN Number : ISRCTN48254013
Eudract Number: 2004-000049-39

This trial is endorsed by the National Cancer Research Network.
This study is Open for Recruitment

Protocol Version 33 - 15 December 2007

Trial Co-ordinator

Michelle Tetlow

ICCG Data Centre
Department of Medical Oncology
Charing Cross Hospital
Fulham Palace Road
London
W6 8RF

• Trial Enquiries: 020 8846 7046
• Fax: 020 8741 0731
• Email: m.tetlow@imperial.ac.uk

Aim

The primary aim is to assess the disease free survival (DFS) benefit of two years adjuvant therapy with the COX-2 inhibitor celecoxib compared with placebo in primary breast cancer patients.

Background

It has recently been recognised that the inflammatory process may provide an environment for the progression of malignant disease. Prostaglandins are synthesised from phospholipids by the action of phospholipase A2 and cyclo-oxygenase. Cox 2 is inducible and its expression is induced by a large range of oncogenes and growth factors. Celecoxib is a selective Cox 2 inhibitor that does not inhibit Cox 1 and therefore does not lead to excessive gastro-intestinal ulceration. This was recently confirmed in a study of more than 8000 patients with osteoarthritis who had reduced side-effects compared with conventional drugs.

One hypothesis of the study is that use of the Cox 2 antagonist Celecoxib following chemotherapy will reduce inflammation around potential micrometastases, and diminish their chance of survival thereby extending the disease free survival and overall survival of patients with breast cancer. Several studies have been done that suggest that anti-inflammatory compounds reduce breast cancer risk.

Aside from the anti inflammatory action, Cox 2 antagonists also have an inhibitory effect on tumour cell invasion and metastases. They induce apoptosis and they also inhibit angiogenesis. Cox 2 inhibitors also inhibit breast cancer cell proliferation in animal models.

Study Design

A multicentre, phase III randomised double-blind, placebo-controlled trial. Patients are randomised between two years celecoxib and placebo in a 2:1 ratio in favour of Celecoxib. Additionally all ER+ and/or PgR+ patients will receive tamoxifen for 2-3 yrs followed by exemestane for 2-3years (total duration 5 years).

Primary End Point

1. Disease free Survival

Secondary End Point

1. Overall Survival
2. The toxicity associated with long term use of celecoxib in primary breast cancer patients
3. Cardiovascular mortality
4. The incidence of second primaries

Target Accrual

2590 patients will be randomised into this study over a 3yr period.