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

PROVENT: A Randomised, Double Blind, Placebo Controlled Feasibility Study to Examine the Clinical Effectiveness of Aspirin and/or Vitamin D3 to Prevent Disease Progression in Men on Active Surveillance for Prostate Cancer

To demonstrate the acceptability and feasibility of recruitment to a randomised chemoprevention study of standard (300mg) or low dose (100mg) aspirin vs. placebo and/or Vitamin D3 vs. placebo in patients enrolled on an Active Surveillance programme for prostate cancer.

The PROVENT study is a randomised, double blind, placebo controlled feasibility study to examine the clinical effectiveness of aspirin and/or Vitamin D3 to prevent disease progression in men on Active Surveillance for prostate cancer

The main outcome measure of the trial is the rate of patient recruitment to a randomised chemoprevention study in men enrolled on an Active Surveillance programme for prostate cancer

Secondary outcomes include the response to treatment as determined by serial multi-parametric magnetic resonance imaging (MRI) of the prostate, biochemical disease progression and histological disease progression after 12 months of therapy and finally toxicity and/or allergy to both aspirin and Vitamin D3.

1. Male subjects aged 16 years or over with an estimated life expectancy of more than three 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 the local 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 at least 10 cores of prostate tissue) in men opting for Active Surveillance as their primary 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 other investigational drug or device study.
3. Current daily use of aspirin or NSAIDs; or daily dietary supplements/medication containing more than 400 IU (10 micrograms per day) Vitamin D; or chronic use (defined as > 6 months continuous daily use) of either aspirin or >400IU Vitamin D within two years 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 including repeat prostate biopsies
6. Known allergy/sensitivity to or intolerance of aspirin, other salicylates or NSAIDs e.g. ibuprofen/ naproxen
7. Prior history of gastro-intestinal bleeding or ulceration, severe dyspepsia or inflammatory 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 untreated hyperparathyroidism
12. Any bowel condition that would make repeat transrectal biopsy hazardous or difficult to perform e.g. recto-urethral fistula, or prior bowel surgery such as abdomino-perineal resection.
13. Any malignancy (other than non-melanoma skin cancer) that has not been in complete remission for five years
14. Any serious co-existent medical condition that would make repeat prostate biopsy hazardous 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), including concomitant 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 3-4 units per day (men)