TIP
Research type
Research Study
Full title
Thrombin Inhibition Preoperatively in Early Breast Cancer
IRAS ID
167520
Contact name
Cliona Kirwan
Contact email
Sponsor organisation
University Hospital of South Manchester
Eudract number
2014-004909-33
Duration of Study in the UK
2 years, 9 months, 1 days
Research summary
Up to 26% of cancer patients develop clots in the legs (deep vein thrombosis) and lungs (pulmonary embolism). Cancer patients who develop clots have a three-fold lower survival than those without clots, implying clots are a surrogate maker of aggressive cancer. Laboratory evidence shows that the clotting system helps cancers grow and spread. We have found that in breast cancer, patients with more aggressive disease (higher stage, faster dividing cells, hormone insensitive) have increased clotting in the tumour and blood.
We hypothesise that anticlotting drugs will have an anti-cancer effect in early breast cancer, through various mechanisms including inhibiting tumour growth, new blood vessel formation and spread (metastasis). A new class of drugs – Novel Oral AntiCoagulants (NOAC), have recently been licensed for prevention of vein clots in orthopaedic surgery and stroke prevention, and have a good safety profile.
Early breast cancer has such excellent survival now that to test such drugs in early breast cancer would require thousands of patients, long follow-up and great expense. The alternative is a more novel clinical trial design where drugs are tested over a short period, in the preoperative setting. Subtle changes in the tumour (biomarkers) are used as surrogate markers for treatment response and long term outcome.
For example Ki67 (marker of rate of tumour cell division) is recognised as such a marker, and decreases in response to only two weeks of anti-oestrogen therapy in oestrogen positive early breast cancer.
In women newly diagnosed with oestrogen negative (associated with increased clotting) early breast cancer and awaiting surgery (usually 3-4 weeks), we shall give 10-14 days of Rivaroxaban (NOAC) prior to surgery. We shall compare blood and tissue taken at the time of diagnosis, with blood and tissue taken at surgery, to determine any cancer inhibitory effects of Rivaroxaban using Ki67 and other biomarkers.
REC name
North West - Liverpool Central Research Ethics Committee
REC reference
15/NW/0406
Date of REC Opinion
13 Jul 2015
REC opinion
Further Information Favourable Opinion