Condition category
Cancer
Date applied
06/04/2014
Date assigned
16/04/2014
Last edited
04/04/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Ms Roseann Kealy

ORCID ID

Contact details

Centre for Cancer Prevention
Wolfson Institute of Preventive Medicine
Charterhouse Square
London
EC1M 6BQ
United Kingdom
+44 20 7882 3520
r.kealy@qmul.ac.uk

Additional identifiers

EudraCT number

2014-001784-13

ClinicalTrials.gov number

Protocol/serial number

PROVENT: Version 3.0

Study information

Scientific 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

Acronym

PROVENT

Study hypothesis

That men enrolled onto an active surveillance programme for the management of prostate cancer will actively participate in a randomised chemoprevention study of standard (300mg) or low dose (100mg) aspirin vs placebo and/or Vitamin D vs placebo.

Ethics approval

London-Hampstead Committee London, 18/11/2014, ref: 14/LO/2033

Study design

Randomised double blind placebo-controlled feasibility study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Prevention

Patient information sheet

See additional files

Condition

Prostate cancer

Intervention

The principal method of randomisation will be by means of a purpose designed web-based application, developed by Barts CTU, which will be accessible to all relevant research staff. Staff will be trained in the use of this application. The applications' Case Report Forms will reaffirm the patient's eligibility and require confirmation that the consent form has been satisfactorily signed and countersigned.

Eligible participants will be randomised into one of 6 arms of the study to receive one of the following:

1. Aspirin 300mg + Vitamin D3
2. Aspirin 300mg + Vitamin D3 placebo
3. Aspirin 100mg + Vitamin D3
4. Aspirin 100mg + Vitamin D3 placebo
5. Aspirin placebo + Vitamin D3
6. Aspirin placebo + Vitamin D3 placebo

Randomised blocks will be used to maintain balance amongst these 6 arms. In addition, the aspirin placebo groups will be block randomised to either small or large aspirin placebo tablets. The allocated study number will correspond to pre-labelled pots of trial medication held in pharmacy.

In the event that the web application is unavailable, a paper backup system will be available, and randomisations may be made using a FAX backup system. Once a patient has been successfully randomised, the enrolment of the patient will be documented on the PROVENT Screening Log.

Dosage:
Vitamin D3: 4,000IU/0.1mg (6 drops) orally daily or matched placebo
Aspirin: 100mg daily orally or matched placebo
Aspirin: 300mg daily orally or matched placebo

Intervention type

Supplement

Phase

Not Applicable

Drug names

Aspirin, Vitamin D3

Primary outcome measures

Rate of patient recruitment to a randomised chemoprevention study in men enrolled on an Active Surveillance programme for prostate cancer. This will be determined by screening logs and screening/randomisation case report forms.

Secondary outcome measures

1. To report response to treatment as determined by serial multi-parametric magnetic resonance imaging (MRI) of the prostate - measured by performing repeat prostate MRI imaging
2. To report biochemical disease progression - measured by measuring serum PSA levels 3 monthly
3. To report histological disease progression - measured by measuring serum PSA levels 3 monthly
4. To report toxicity and/or allergy to both aspirin and Vitamin D. Toxicity will be evaluated 3 monthly using the Adverse Events Case Report Form and the patient diary cards on which patients will record side effects and adverse reactions
5. To evaluate an association between androgens and disease progression. Blood will be taken to measure serum androgen levels every 6 months - at baseline, 6 months, 12 months and 18 months
6. To evaluate markers of disease progression. Urinary markers of disease progression (PCA3 and TMPRSS2-ERG) will be evaluated at baseline and 12 months. Tissue will be collected from the baseline and 12 month prostate biopsies for Cell Cycle Progression scores.

Overall trial start date

01/10/2014

Overall trial end date

31/10/2019

Reason abandoned

Eligibility

Participant inclusion criteria

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. All subjects must have had Magnetic Resonance Imaging (MRI) of the prostate with targeted biopsy of any lesions identified
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 for Inclusion:
1. Gleason score 6 or 7
2. Clinical and radiological stage <T3
3. Serum PSA of 15.0 ng/ml or below
Less than 10mm of cancer in a single core

7. Patients must have undergone a multi-parametric MRI deemed assessable by the local radiologist, and any lesions seen must have undergone targeted biopsy (transrectal or transperineal) within 12 months of study enrolment.

Participant type

Patient

Age group

Adult

Gender

Male

Target number of participants

102

Participant exclusion criteria

1. Previously treated prostate cancer (including radiotherapy, hormone therapy, brachytherapy or surgery)
2. Current enrolment in an investigational drug, device or other clinical research study or participation in such a study within 30 days of randomisation
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 Vitamin D within two years of study enrolment
4. Current or previous use of 5-alpha-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 (¡Ýstage 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 deficiency
17. Pre-existing macular degeneration
18. All contraindications to aspirin and Vitamin D, including concomitant therapy with any medication that may interact with aspirin or Vitamin D (see section 4.10)
19. Regular consumption of alcohol units greater than the recommended daily limit of 3-4 units per day (men)

Recruitment start date

16/12/2016

Recruitment end date

16/12/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Centre for Cancer Prevention
London
EC1M 6BQ
United Kingdom

Sponsor information

Organisation

Queen Mary University of London (UK)

Sponsor details

Representative of Sponsor:
Sally Burtles
Director of Research Development
Joint Research Management Office
QM Innovation Building
5 Walden Street
London
E1 2EF
United Kingdom
+44 207 882 7265
sponsorsrep@bartshealth.nhs.uk

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Bart's and the London Charity (UK) - Clinical Trials Awards and Advisory Committee (CTAAC) endorsed

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal. Any information used for publication in peer reviewed journals will be anonymised and presented at aggregate, and not individual, level. Barts & the London Charity, and CR-UK will be informed of the results. In addition, they will be disseminated to the participants via the PROVENT website.

IPD sharing plan:
The current data sharing plans for the current study are unknown and will be made available at a later date

Intention to publish date

30/06/2020

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

03/04/2017: Primary study contact changed from Mr Paul Cathcart to Ms Roseann Kealy. Cancer Help UK lay summary link added to plain English summary field. Updated ethics approval. Added publication and dissemination plan. Study end date was updated from 01/10/2017 to 31/10/2019. Recruitment dates changed from 01/10/2017 - 01/10/2017 to 16/12/2016 - 16/12/2017. Sponsor representative changed from Gerry Leonard to Sally Burtles. Protocol version was updated from Version 1.0 to Version 3.0 06/02/2017: Internal review.