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

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.

• Male subjects aged 16 years or over with an estimated life expectancy of more than three years
• Willing and able to provide written informed consent
• Corrected serum calcium ≤ 2.65mmol/l
• No previous treatment for prostate cancer (including surgery, hormone therapy, radiotherapy, cryotherapy)
• 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.
• 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

• Previously treated prostate cancer (including radiotherapy, hormone therapy, brachytherapy or surgery)
• Currently enrolled, or has been a participant within the last 30 days, in any other investigational drug or device study.
• 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
• Current or previous use of 5-α reductase inhibitors such as finasteride or dutasteride
• Not willing to comply with the procedural requirements of this protocol including repeat prostate biopsies
• Known allergy/sensitivity to or intolerance of aspirin, other salicylates or NSAIDs e.g. ibuprofen/ naproxen
• Prior history of gastro-intestinal bleeding or ulceration, severe dyspepsia or inflammatory bowel disease
• Haemophilia or other bleeding diatheses
• Prior history of renal stone disease
• Chronic renal disease (≥stage 4)
• Known hypercalcaemia (corrected serum calcium >2.65 mmol/l) or untreated hyperparathyroidism
• 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.
• Any malignancy (other than non-melanoma skin cancer) that has not been in complete remission for five years
• Any serious co-existent medical condition that would make repeat prostate biopsy hazardous e.g. anti-coagulation requiring continuous administration
• Severe Asthma
• G6PD ( glucose-6-phosphate dehydrogenase) deficiency
• Pre-existing macular degeneration
• 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)
• Tuberculosis
• Regular consumption of alcohol units greater than the recommended daily limit of 3-4 units per day (men)