Characterisation of BRAF and MEK Inhibitor Cardiovascular Toxicity
Research type
Research Study
Full title
Biomarker and Imaging Characterisation of BRAF and MEK Inhibitor-Induced Cardiovascular Toxicity: A Prospective Study in Patients with Cancer (BIOCOBRA-Tox)
IRAS ID
290396
Contact name
Ninian Lang
Contact email
Sponsor organisation
NHS Greater Glasgow and Clyde
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Survival rates in cancer patients have been improving over the last few decades, particularly since the introduction of newer, more-targeted chemotherapy agents. BRAF and MEK inhibitors (usually used in combination) have been used in a variety of malignancies but are particularly used in the treatment of patients with melanoma for whom they have substantially improved outcomes. However, since their introduction, it has become clear that these drugs have cardiovascular side effects, notably high blood pressure (hypertension) and can cause impaired pumping of the heart (left ventricular systolic dysfunction [LVSD]).
These side effects can have a significant impact on patients' physical health as well as leading to the withdrawal of important cancer treatment. The mechanisms by which LVSD develops with these drugs are unclear and have not been well-described to date. The ability of blood vessels to contract and relax may be impaired by these drugs and this may lead to the development of LVSD.The aim of this study is to investigate the effect of BRAF and MEK inhibitors on blood vessels, as well as left ventricular function and to understand their effects on blood markers of heart and blood vessel function.
This study will aim to recruit patients diagnosed with cancer who are eligible to receive treatment with BRAF/MEK inhibitors at the Beatson West of Scotland Oncology Centre. The CT scans used as part of their usual care , will be used to examine the aorta and heart arteries. Participants will undergo echocardiography and regular blood pressure monitoring. Additionally, the ability of their arteries to enlarge (dilate) and the number of small blood vessels (capillaries) in their fingertips measured with special machines (EndoPat and nailfold capillaroscopy). Blood and urine will be collected. Patients will also be invited to undergo detailed magnetic resonance imaging (MRI) scans of the heart (this is optional).
REC name
West of Scotland REC 5
REC reference
20/WS/0166
Date of REC Opinion
24 Nov 2020
REC opinion
Favourable Opinion