PROVENT

Full Title: 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

Study acronym: PROVENT

Sponsor: Queen Mary University of London

Funder(s): Barts and the London Charity; plus support via the Centre for Cancer Prevention & ECMC funding structure

Chief Investigator: Prof Greg Shaw, Professor of Urology, University College London Hospitals

Registration: https://clinicaltrials.gov/study/NCT03103152

Background:

Active surveillance is widely used for men with low-risk prostate cancer to monitor the disease while delaying treatment unless progression occurs. Although effective, many men experience anxiety during monitoring, and there is increasing interest in whether common, inexpensive medications might help slow disease progression. Aspirin and Vitamin D3 both have biological properties suggesting potential anticancer benefits. PROVENT was created as a feasibility study to determine whether these treatments could be safely administered, whether men on surveillance would participate, and whether a larger chemoprevention trial would be practical and scientifically worthwhile.

---

Purpose of the Study:

The study aimed to assess whether men on active surveillance for prostate cancer would be willing to enrol in a randomised trial and take daily aspirin (either 300 mg or 100 mg), Vitamin D3, or matched placebos. The feasibility work focused on recruitment, adherence, safety, and the practical considerations necessary to design a future, larger-scale trial investigating whether these agents can reduce disease progression.

---

Recruitment Status:

- Status: Complete - feasibility study concluded

- First participant enrolled: 16/12/2016

- Date of final enrolment: 16/12/2017

- Total participants enrolled: 130

---

Study Objectives:

PROVENT set out to determine whether a combined chemoprevention trial using aspirin and/or Vitamin D3 could be successfully delivered in an active surveillance population. The objectives included understanding the willingness of patients to take part, assessing the safety of the interventions, monitoring adherence, and exploring whether genetic testing of diagnostic biopsy tissue could help identify men at higher risk of progression who may benefit most from additional treatment.

---

Participant Experience:

Eligible men on active surveillance were invited to take part and, after providing informed consent, were randomised to one of several treatment arms involving aspirin, Vitamin D3, or placebo. Participants took the allocated study medication for 12 months and continued standard clinical surveillance during that period. Safety was regularly monitored, and men were encouraged to report any side effects or concerns.

---

Study Results:

The feasibility study enrolled 104 eligible participants (of the 130 consented), and although it was not designed to evaluate treatment effectiveness, it generated valuable insights (see below) for planning a future full-scale trial.

Acceptability and Recruitment

The study demonstrated excellent willingness to participate, with an 80% acceptance rate among eligible men. This suggests that a larger randomised trial within this clinical setting is achievable and would likely yield meaningful uptake.

Genetic Testing and Risk Stratification

In 81% of cases, residual biopsy tissue was successfully used for genetic analysis. This indicates that genomic testing at diagnosis could help identify men at greater risk of disease progression and may assist future stratified trial designs.

Safety and Adherence

Medication adherence was high (89% across treatment arms). Aspirin was generally well tolerated, though one participant experienced rectal bleeding requiring withdrawal, and two experienced minor side effects. Vitamin D3 appeared safe with no notable adverse events. One participant died from an unrelated cause during the study, consistent with expected background mortality.

Early Treatment Decisions and Patient Anxiety

Nine participants chose to undergo treatment before the 12-month mark, despite no evidence of progression, likely reflecting anxiety associated with ongoing surveillance. A further nine withdrew for reasons including side effects and unrelated medical issues. These findings highlight the need for better supportive information and possibly risk-stratification tools, such as genetic testing, in future research to help reduce surveillance-related anxiety.

Acknowledgements:

We are grateful to all the men who participated in PROVENT and contributed to this important area of prostate cancer research.

Study Completion Date:

• 31/03/2020 - Completed