The ExPeCT (Examining Exercise, Prostate Cancer and Circulating Tumour Cells) trial: study protocol for a randomised controlled trial

Abstract

BackgroundProstate cancer (PrCa) is the second most common cancer in Ireland. Many men present with locally advanced or metastatic cancer for whom curative surgery is inappropriate. Advanced cancer patients are encouraged to remain physically active and therefore there is a need to investigate how patients with metastatic disease tolerate physical activity programmes. Physical activity reduces levels of systemic inflammatory mediators and so an aerobic exercise intervention may represent an accessible and cost-effective means of ameliorating the pro-inflammatory effects of obesity and subsequently decrease poor cancer-specific outcomes in this patient population. This study will assess the feasibility and safety of introducing a structured aerobic exercise intervention to an advanced cancer population. This study will also examine if the evasion of immune editing by circulating tumour cells (CTCs) is an exercise-modifiable mechanism in obese men with prostate cancer.MethodsThis international multicentre prospective study will recruit men with metastatic prostate cancer. Participants will be recruited from centres in Dublin (Ireland) and London (UK). Participants will be divided into exposed and non-exposed groups based on body mass index (BMI) ≥ 25 kg/m2 and randomised to intervention and control groups. The exercise group will undertake a regular supervised aerobic exercise programme, whereas the control group will not. Exercise intensity will be prescribed based on a target heart rate monitored by a polar heart rate monitor. Blood samples will be taken at recruitment and at 3 and 6 months to examine the primary endpoint of platelet cloaking of CTCs. Participants will complete a detailed questionnaire to assess quality of life (QoL) and other parameters at each visit.DiscussionThe overall aim of the ExPeCT trial is to examine the relationship between PrCa, exercise, obesity, and systemic inflammation, and to improve the overall QoL in men with advanced disease. Results will inform future work in this area examining biological markers of prognosis in advanced prostate cancer.Trial registrationClinicaltrials.gov NLM identifier: NCT02453139. Registered on 12 May 2015. This document contains excerpts from the ExPeCT trial protocol Version 1.5, 28 July 2016.

Platelet cloaking of circulating tumour cells in patients with metastatic prostate cancer: Results from ExPeCT, a randomised controlled trial

“…The ExPeCT Trial protocol has previously been described elsewhere including inclusion and exclusion criteria and randomisation procedures [ 11 ]. Briefly, ExPeCT was a multi-centre (Ireland and London) prospective study designed to examine the relationship between exercise, platelet cloaking and CTCs in patients with metastatic PrCa [ 11 ]. Participants were randomised into exercise or control arms and participated in the trial for six months.…”

“…The assessment and follow-up period for the primary endpoint of this study took place between October 2014 and November 2017. Each participant received a participant identifier number (PIN) and the computer programme Graphpad was used to randomly assign a treatment group to each PIN [ 11 ]. Gatekeepers informed the research team of participant allocation.…”

“…The exercise programme has been described in detail previously [ 11 ]. Participants randomised into the exercise group participated in moderate-to-vigorous intensity aerobic exercise comprising a weekly class for 3 months (supervised) and home-based aerobic exercise for 3 months (unsupervised).…”

“…Sample size and study power have been described previously in the study protocol [ 11 ]. Briefly, the study aimed to recruit 200 participants over the lifetime of the study, evenly divided between the exercise group and the control group.…”

“…Briefly, the study aimed to recruit 200 participants over the lifetime of the study, evenly divided between the exercise group and the control group. Study power was calculated based on data from a study of ovarian cancer cell lines [ 11 , 17 ], which showed approximately 2% platelet adhesion and a study of PrCa CTCs [ 18 ] that determined a mean of 75 CTCs with a standard deviation (SD) of 333. If the SD of platelet adhesion in PrCa CTCs is proportionate to ovarian cancer cell lines (6.66%), then it was hypothesized that there was sufficient power to detect a difference of 2.65% with 100 participants in both exposed and non-exposed groups, determined by independent t-testing.…”