Trial to test the feasibility of an exercise and metformin intervention for men with prostate cancer

INTERVENTION: Participants are randomised into two groups, the intervention or the control. The intervention will be either physical activity or to take metformin. Each participant will be randomised within the treatment group to either physical activity or control, and then to either metformin or control, resulting in 4 groups: 1. Physical activity and metformin 2. Physical activity only 3. Metformin only 4. No intervention (control) Participants in the physical activity only group will be asked to undertake brisk walking for 30‐minutes per day, 5‐days per week, on top of their usual activity, with the additional aim to walk 10,000 steps per day. Some participants in this group will be provided a Garmin wrist‐worn activity monitor which will provide real‐time feedback and motivational reminders ‐ these will be provided to participants who are willing to wear them. Offers to wear a Garmin will be managed to a certain extent, to ensure an even spread across the treatment groups (active surveillance, radical prostatectomy, radiotherapy), but there will be no formal randomisation for these. Participants in the metformin only group will take one 500mg of modified release Metformin, once a day with food. Participants in the physical activity and metformin group will be asked to undertake the same activities as both the physical activity only and metformin only groups. Participants in the control group will not receive intervention instructions or training. The intervention period is 6 months, beginning close to start of cancer treatment for participants waiting to receive prostatectomy or radiotherapy. For participants receiving active surveillance treatment, the intervention period will be 6 months after the start of active surveillance, to align end of intervention with the routine biopsy that takes place at 12 months post‐diagnosis for these patients. CONDITION: Prostate cancer ; Cancer ; Localised and locally advanced malignant neoplasm of prostate PRIMARY OUTCOME: 1. Proportion of eligible men who agree to be randomized; 2. Adherence to intervention, calculated separately for physical activity and metformin, assessed at 3 and 6 months after start of intervention. ; 2.1. For physical activity, adherence will be assessed by step count, recorded by pedometer and reported by the participant.; 2.2. Metformin will be assessed by a count of the pills returned by the participant to the research clinics. In addition, blood samples will be taken which may be examined for metformin.; 2.3. Both of these will be assessed for participants in the physical activity and metformin group INCLUSION CRITERIA: 1. Localised or locally advanced prostate cancer 2. Due to undergo radiotherapy or radical prostatectomy, or due to begin the active surveillance pathway 3. Due to receive treatment at Southmead Hospital, North Bristol NHS Trust or Bristol Haematology & Oncology Centre (University Hospitals Bristol NHS Trust) 4. Capacity to consent for themselves as judged by a member of the research team with appropriate training and experience 5. Aged 18 or over 6. Have sufficient understanding of the English language, including being able to read and speak English at a basic level SECONDARY OUTCOME: 1. Intervention tolerability, assessed using qualitatively collected data and reporting of adverse events from qualitative interviews for selected participants after the end of the 6 month intervention period; 2. Trial retention, assessed by number of participants successfully followed‐up at the end of the 6 month trial, as a proportion of those who we recruited to the trial and randomised into a study arm at the start of the trial); 3. Feasibility of measuring prostate specific antigen (PSA) level, assessed using a blood sample at the baseline and 6 month follow up; 4. Feasibility of measuring insulin‐like growth factor I (IGF‐I), assessed using a blood sample at the baseline and 6 month follow up; 5. Feasibility of demonstrating methylation and gene expression profiles in prostate tissue and blood, assessed using blood and tissue samples (prostate tissue removed during surgery and tissue removed during biopsy as part of standard care) at the baseline and 6 months; 6. Feasibility of assessing physical activity levels, self‐reported using the Godin Exercise Leisure‐time Questionnaire at the baseline, 3, 6 and 12 months; 7. Urinary symptoms, assessed using the International Continence Society male ‐ Short Form (ICSmale‐SF) at the baseline and 3, 6 and 12 month follow up, along with 7 weeks following main consent for the surgical patients; 8. Psychological factors, assessed at the baseline and 3, 6 and 12 month following using:; 8.1. Profile of Mood States – Short Form (POMS‐SF); 8.2. Benefit Finding Scale; 9. Patient function and bother after prostate cancer treatment, assessed using he Expanded Prostate Cancer Index Composite (EPIC‐26) at the baseline and 3, 6 and 12 months follow up; 10. Health beliefs, assessed at the baseline and 3, 6 and 12 month follow up using:; 10.1. Items from the Theory of Planned Behaviour (Ajzen, 1991) ‐ there is no standard TPB questionnaire but Ajzen provided advice on questionnaire construction and gave examples and the questionnaire was designed to be applicable to this study; 10.2. Items based on work from Prochaska and Di Clemente's Transtheoretical Model of Stages and Processes of Change; 11. Quality of life measures, assessed using the Functional Assessment of Cancer Therapy‐Prostate (FACT‐P) at the baseline and 3, 6 and 12 month follow up; 12. Cancer related fatigue, assessed using the Functional Assessment of Chronic Illness Therapy‐Fatigue (FACIT‐Fatigue) and EuroQol five dimensions questionnaire (EQ‐5D) at the baseline and 3, 6 and 12 month follow up. This is additionally collected at 6 weeks following completion of radiotherapy for the radiotherapy patients, which is approximately 4.5 months after main consent ; 13. General lifestyle factors, assessed using self‐reported levels of smoking and drinking at the baseline, 3, 6 and 12 months; 14. Feasibility of men with localised prostate cancer wearing wrist worn activity trackers, assessed by qualitative interview and monitoring form at the end of the 6 month intervention period; 15. Impact of wrist worn activity trackers on adherence to the physical activity intervention, assessed using 7 day step count on monitoring form and data recorded by wrist worn activity trackers at the baseline, 3, 6 and 12 months; 16. Weight and body mass index, measured by a nurse at the baseline; 17. Attitudes and views of men about physical activity and metformin interventions and participation within the trial,. assessed using qualitatively collected data;