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

Phase 2

Completed

Conditions: Prostate Cancer

Interventions: Drug: High dose Aspirin, Vitamin D placebo
Drug: Low dose Aspirin , Vitamin D
Drug: High dose Aspirin & Vitamin D
Drug: Low dose Aspirin, Vitamin D placebo
Drug: Aspirin Placebo, Vitamin D
Drug: Aspirin placebo, Vitamin D placebo

Registration Number: NCT03103152

Lead Sponsor: Queen Mary University of London

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 104

Inclusion Criteria

Not provided

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Aspirin Placebo, Vitamin D	Aspirin Placebo, Vitamin D	Aspirin placebo and Vitamin D active ingredient - Vigantol® Oil
High dose Aspirin, Vitamin D placebo	High dose Aspirin, Vitamin D placebo	high dose aspirin (300mgs) daily and Vitamin D placebo (Miglyol®812 Oil)
Low dose Aspirin , Vitamin D	Low dose Aspirin , Vitamin D	Low dose aspirin (100mgs) daily \& Vitamin D 4,000 IU (0.1mg) per day
High dose Aspirin & Vitamin D	High dose Aspirin & Vitamin D	Aspirin high dose (300mgs) daily \& Vitamin D 4,000 IU (0.1mg) per day
Low dose Aspirin, Vitamin D placebo	Low dose Aspirin, Vitamin D placebo	Low dose aspirin (100mgs) daily and Vitamin D placebo (Miglyol®812 Oil)
Aspirin Placebo, Vitamin D	Low dose Aspirin , Vitamin D	Aspirin placebo and Vitamin D active ingredient - Vigantol® Oil
High dose Aspirin, Vitamin D placebo	Aspirin placebo, Vitamin D placebo	high dose aspirin (300mgs) daily and Vitamin D placebo (Miglyol®812 Oil)
Aspirin placebo, Vitamin D placebo	Aspirin placebo, Vitamin D placebo	Aspirin placebo and Vitamin D placebo - Miglyol®812 Oil

Primary Outcome Measures

Name	Time	Method
Rate of Patient Recruitment to a Randomised Chemoprevention Study in Men Enrolled on an Active Surveillance Programme for Prostate Cancer. Number Accrued Per Month.	12 months	The proportion of eligible patients that join the trial over the 12-month trial recruitment period.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Biochemical (PSA) Disease Progression	12 months	50% increase in serum Prostate Specific Antigen at 12 months from baseline.
Number of Participants With Histological Disease Progression	3 years	Histological disease progression will be defined as an increase in Gleason scores from: Gleason 3+3 to Gleason score 7 or higher Gleason 3+4 (score 7) to 4+3 (score 7) or Gleason 4+3 to a higher score Or a 50% increase in maximum cancer core length (MCCL)
Response to Treatment as Determined by Serial Multi-parametric Magnetic Resonance Imaging (MRI) of the Prostate. New Lesion Present or Existing Lesion + or - in Size.	3 years	Radiological progression was defined as 'development of a Prostate Imaging-Reporting and Data System (PI-RADS) 4/5 lesion (17) on mpMRI, where no lesion was identified before, 33% volume increase in the size of the lesion, or radiological upstaging to T3 or above based on local site reports.' Absence of these features represented radiologically stable disease. Lesion on multi-parametric imaging where no MRI lesion at screening. An MRI scan shows a screening + or - in volume by \> 33%, or an upgrading of MRI stage of disease to ≥3.
Number of Patients With Adverse With Toxicity, Allergy or Symptoms From Aspirin or Vitamin D	18 months + 30 days	Aspirin toxicity: Haemorrhagic stroke, anaphylaxis following administration, gastrointestinal bleeding requiring intervention (both medical and surgical) Vitamin D3 toxicity: Hypercalcaemia, Anaphylaxis

Trial Locations

Locations (7): Darent Valley Hospital
🇬🇧
Dartford, United Kingdom
University Hospital of Wales
🇬🇧
London, United Kingdom
University Hospital UHCW NHS Trust
🇬🇧
London, United Kingdom
University College Hospital London
🇬🇧
London, United Kingdom
St Bartholomews Hospital London, Bart's and the London school of Medicine
🇬🇧
London, United Kingdom
Southampton General Hospital
🇬🇧
Southampton, United Kingdom
Homerton Hospital
🇬🇧
London, United Kingdom