EXERTION: Exercise Training In Ovarian cancer: a phase 1 proof-of-principle study

Dr Gillian Prue; Dr Susan Clarke; Prof Richard Kennedy (CCRCB)

Background: Due to late presentation, women with ovarian cancer tend to have a poor prognosis. They also suffer severe, persistent fatigue (Prue et al., 2010). Physical activity (PA) has been shown to be safe, beneficial and is recommended for cancer survivors (Ballard-Barbash et al., 2012), it is known to help alleviate fatigue (Cramp et al., 2012), and there is growing evidence that it may improve survival (Ballard-Barbash et al., 2012). This may be due to modifications in the insulin pathway (Irwin et al., 2009), and there is accumulating evidence that insulin/IGF pathways could act as a good therapeutic target in ovarian cancer (Beauchamp et al., 2010).
To date, there is only one large scale RCT that has investigated the impact of physical activity in ovarian cancer and its impact on QOL and fatigue (Zhou et al., 2015). This utilised a home-based walking programme rather than supervised non-linear exercise training. Traditionally exercise in oncology trials have adopted the homogeneous generic model of moderate-intensity supervised or home-based exercise (Sasso et al., 2015). Despite the proven efficacy of the principles of training with athletes, non-linear training has not been translated into the design of exercise prescriptions in oncology populations. Through this project we hope to develop and determine the feasibility of this innovative approach to exercise in oncology, with the view of optimising exercise training in ovarian cancer and maximising the impact it could have on symptoms and survival.

The impact of non-linear exercise training on symptoms and survival in ovarian cancer is novel. We are unaware of any study that has tested the impact of non-linear exercise training on patient reported outcomes and biomarkers of ovarian cancer symptoms and prognosis.

Aim: The overall aim of the programme of work is to improve overall survival and subjective fatigue in women with ovarian cancer. This proposed study will constitute the first step towards the overall aim. It will determine the feasibility of an innovative, non-linear exercise programme for women with ovarian cancer and give an initial indication of its impact on biomarkers of ovarian cancer prognosis and on its ability to improve fatigue in this population.
Methodology: We are proposing to conduct a proof-of-principle phase 1 feasibility study. This will include: the development of a suitable prescriptive, individualised exercise programme utilising the ‘principles of training’; identification of appropriate biomarkers; feasibility testing and exploratory evaluation. For this proof of principle study we will target patients with high grade serous ovarian cancer on second line treatment resulting in stable or partial response (persistent disease) on completion of therapy. These patients will typically have a treatment free period in which the study could be run and they will have biochemical evidence of disease in their blood (e.g. elevated CA125 and IGF). We anticipate that we will get results quickly if exercise affects the levels of these.

Feasibility will be determined via a single arm trial involving 10 – 15 patients. This will be used to test the acceptability of the programme, recruitment and retention rates, acceptability of fatigue outcome measurement and provide useful data for the calculation of an effect size for a larger trial.
An exploratory evaluation of the exercise programme will also be conducted qualitatively with participants, non-participants and those who withdraw from the programme. This will be used to optimise the intervention for future effectiveness studies.

Expected Outcomes: There is limited evidence that ovarian (or any) cancer patients can participate in non-linear training. We aim to demonstrate the safety and acceptability of utilising the principles of training (non-linear approach) in exercise oncology. The long term goal is to target Stage III high grade serous ovarian cancer patients on first line treatment who have been optimally debulked and have had optima chemotherapy via a prospective RCT. This will allow us to determine whether we can maintain improvements in fatigue and extend survival or time to recurrence. This will provide definitive evidence on the effectiveness of exercise training to enhance survival and alleviate the debilitating fatigue suffered by this population group.

Required qualifications: Candidates should have completed or be about to complete an undergraduate degree in Nursing, Biomedical or Exercise Science, Physiotherapy or any related allied health professional degree (2:1). An MSc level degree is desirable but not essential. To be eligible for consideration for a studentship candidates must have been ordinarily resident in the UK or European Economic Area (EEA) since September 2013 (with no immigration restrictions).

Desired research skills: The candidate should have undergraduate experience in research methods and have knowledge of both quantitative and qualitative methods. Experience in exercise physiology, the development of exercise programmes, serological analysis of biomarkers or biochemical assays such as ELISA would be desirable.
The successful applicant will receive a three year studentship which will cover UK/EU tuition fees and a stipend to cover living expenses. The studentship should preferably start on 01 October 2016.

If you wish to be considered for a studentship, please complete the following two steps:
- Email an up to date CV and a covering letter explaining why you want to undertake a PhD in the School of Nursing and Midwifery to Amber Mulholland at [Email Address Removed].
- Complete the online application by clicking here for the QUB Postgraduate Applications Portal.
The closing date for applications is Friday 12 February 2016. Interviews for shortlisted candidates are expected to take place the week commencing 22 February.