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

Prostate Cancer Clinical Trial

— PROVENT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03103152
• Other study ID #: isrctn91422391
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: December 2016
• Est. completion date: March 31, 2020

Study information

• Verified date: March 2020
• Source: Queen Mary University of London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: March 31, 2020
• Est. primary completion date: March 31, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 16 Years to 100 Years

Eligibility

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-a 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)

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• High dose Aspirin & Vitamin D
Aspirin 1 x 300mg tablet daily & Vitamin D 4,000IU daily. (8 drops).
• High dose Aspirin, Vitamin D placebo
Aspirin 1 x 300mg tablet daily & Vitamin D placebo (8 drops).
• Low dose Aspirin , Vitamin D
Aspirin 1 x 100mg tablet daily & Vitamin D 4,000IU daily. (8 drops).
• Low dose Aspirin, Vitamin D placebo
Aspirin 1 x 100mg tablet daily & Vitamin D placebo 8 drops daily.
• Aspirin Placebo, Vitamin D
Aspirin 1 x 300mg placebo tablet daily & Vitamin D 4,000IU daily. (8 drops).
• Aspirin placebo, Vitamin D placebo
Aspirin 1 x 100mg placebo tablet daily & Vitamin D 4,000IU daily. (8 drops).

Locations

Country	Name	City	State
United Kingdom	Darent Valley Hospital	Dartford
United Kingdom	Homerton Hospital	London
United Kingdom	St Bartholomews Hospital London, Bart's and the London school of Medicine	London
United Kingdom	University College Hospital London	London
United Kingdom	University Hospital of Wales	London
United Kingdom	University Hospital UHCW NHS Trust	London
United Kingdom	Southampton General Hospital	Southampton

Sponsors (3)

Lead Sponsor	Collaborator
Queen Mary University of London	Barts and the London School of Medicine and Dentistry, Cancer Research UK

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Patient Recruitment to a Randomised Chemoprevention Study in Men Enrolled on an Active Surveillance Programme for Prostate Cancer. Number Accrued Per Month.	The proportion of eligible patients that join the trial over the 12-month trial recruitment period.	12 months
Secondary	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.	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.	3 years
Secondary	Number of Participants With Biochemical (PSA) Disease Progression	50% increase in serum Prostate Specific Antigen at 12 months from baseline.	12 months
Secondary	Number of Participants With Histological Disease Progression	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)	3 years
Secondary	Number of Patients With Adverse With Toxicity, Allergy or Symptoms From Aspirin or Vitamin D	Aspirin toxicity: Haemorrhagic stroke, anaphylaxis following administration, gastrointestinal bleeding requiring intervention (both medical and surgical); Vitamin D3 toxicity: Hypercalcaemia, Anaphylaxis	18 months + 30 days