A Study to Examine the Effectiveness of Aspirin and/or Vitamin D3 to Prevent Prostate Cancer Progression

1. Male subjects aged 16 years or over with an estimated life expectancy of more thanthree years
2. Willing and able to provide written informed consent
3. Corrected serum calcium ≤ 2.65mmol/l
4. No previous treatment for prostate cancer (including surgery, hormone therapy,radiotherapy, cryotherapy)
5. Must have undergone a multi-parametric MRI of the prostate, deemed assessable by thelocal radiologist, and any lesions seen must have undergone targeted biopsy, (transrectal or transperineal) within 12 months of study registration.
6. Histologically confirmed prostate cancer* following prostate biopsy (including atleast 10 cores of prostate tissue) in men opting for Active Surveillance as theirprimary cancer therapy.

• PROVENT Prostate Cancer Criteria. All must be met for Inclusion:
• Gleason score 6 or 7 (Gleason 3+3 or 3+4)
• Clinical and radiological stage <T3
• Serum Prostate Specific Antigen (PSA) ≤15.0 ng/ml
• Less than 10mm of cancer in a single core

Exclusion Criteria:

1. Previously treated prostate cancer (including radiotherapy, hormone therapy,brachytherapy or surgery)
2. Currently enrolled, or has been a participant within the last 30 days, in any otherinvestigational drug or device study.
3. Current daily use of aspirin or NSAIDs; or daily dietary supplements/medicationcontaining more than 400 IU (10 micrograms per day) Vitamin D; or chronic use (definedas > 6 months continuous daily use) of either aspirin or >400IU Vitamin D within twoyears of study enrolment
4. Current or previous use of 5-α reductase inhibitors such as finasteride or dutasteride
5. Not willing to comply with the procedural requirements of this protocol includingrepeat prostate biopsies
6. Known allergy/sensitivity to or intolerance of aspirin, other salicylates or NSAIDse.g. ibuprofen/ naproxen
7. Prior history of gastro-intestinal bleeding or ulceration, severe dyspepsia orinflammatory bowel disease
8. Haemophilia or other bleeding diatheses
9. Prior history of renal stone disease
10. Chronic renal disease (≥stage 4)
11. Known hypercalcaemia (corrected serum calcium >2.65 mmol/l) or untreatedhyperparathyroidism
12. Any bowel condition that would make repeat transrectal biopsy hazardous or difficultto perform e.g. recto-urethral fistula, or prior bowel surgery such asabdomino-perineal resection.
13. Any malignancy (other than non-melanoma skin cancer) that has not been in completeremission for five years
14. Any serious co-existent medical condition that would make repeat prostate biopsyhazardous e.g. anti-coagulation requiring continuous administration
15. Severe Asthma
16. G6PD ( glucose-6-phosphate dehydrogenase) deficiency
17. Pre-existing macular degeneration
18. All contraindications to aspirin and Vitamin D3 (e.g. Sarcoidosis), includingconcomitant therapy with any medication that may interact with aspirin or Vitamin D3 (see section 4.10)
19. Tuberculosis
20. Regular consumption of alcohol units greater than the recommended daily limit of 3-4units per day (men)