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

Primary Purpose

Prostate Cancer

Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
High dose Aspirin & Vitamin D
High dose Aspirin, Vitamin D placebo
Low dose Aspirin , Vitamin D
Low dose Aspirin, Vitamin D placebo
Aspirin Placebo, Vitamin D
Aspirin placebo, Vitamin D placebo
Sponsored by
Queen Mary University of London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Prostate Cancer focused on measuring Prostate Cancer, Active Surveillance, Chemo-prevention

Eligibility Criteria

16 Years - 100 Years (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers
  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-α 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)

Sites / Locations

  • Darent Valley Hospital
  • University Hospital of Wales
  • University Hospital UHCW NHS Trust
  • St Bartholomews Hospital London, Bart's and the London school of Medicine
  • University College Hospital London
  • Homerton Hospital
  • Southampton General Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Experimental

Experimental

Arm Label

High dose Aspirin & Vitamin D

High dose Aspirin, Vitamin D placebo

Low dose Aspirin , Vitamin D

Low dose Aspirin, Vitamin D placebo

Aspirin Placebo, Vitamin D

Aspirin placebo, Vitamin D placebo

Arm Description

Aspirin high dose (300mgs) daily & Vitamin D 4,000 IU (0.1mg) per day

high dose aspirin (300mgs) daily and Vitamin D placebo (Miglyol®812 Oil)

Low dose aspirin (100mgs) daily & Vitamin D 4,000 IU (0.1mg) per day

Low dose aspirin (100mgs) daily and Vitamin D placebo (Miglyol®812 Oil)

Aspirin placebo and Vitamin D active ingredient - Vigantol® Oil

Aspirin placebo and Vitamin D placebo - Miglyol®812 Oil

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Number of Participants With Biochemical (PSA) Disease Progression
50% increase in serum Prostate Specific Antigen at 12 months from baseline.
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)
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

Full Information

First Posted
November 21, 2016
Last Updated
March 28, 2023
Sponsor
Queen Mary University of London
Collaborators
Barts and the London School of Medicine and Dentistry, Cancer Research UK
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1. Study Identification

Unique Protocol Identification Number
NCT03103152
Brief Title
A Study to Examine the Effectiveness of Aspirin and/or Vitamin D3 to Prevent Prostate Cancer Progression
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
December 2016 (undefined)
Primary Completion Date
March 31, 2020 (Actual)
Study Completion Date
March 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Queen Mary University of London
Collaborators
Barts and the London School of Medicine and Dentistry, Cancer Research UK

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
Prostate Cancer, Active Surveillance, Chemo-prevention

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Factorial Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
104 (Actual)

8. Arms, Groups, and Interventions

Arm Title
High dose Aspirin & Vitamin D
Arm Type
Experimental
Arm Description
Aspirin high dose (300mgs) daily & Vitamin D 4,000 IU (0.1mg) per day
Arm Title
High dose Aspirin, Vitamin D placebo
Arm Type
Experimental
Arm Description
high dose aspirin (300mgs) daily and Vitamin D placebo (Miglyol®812 Oil)
Arm Title
Low dose Aspirin , Vitamin D
Arm Type
Experimental
Arm Description
Low dose aspirin (100mgs) daily & Vitamin D 4,000 IU (0.1mg) per day
Arm Title
Low dose Aspirin, Vitamin D placebo
Arm Type
Placebo Comparator
Arm Description
Low dose aspirin (100mgs) daily and Vitamin D placebo (Miglyol®812 Oil)
Arm Title
Aspirin Placebo, Vitamin D
Arm Type
Experimental
Arm Description
Aspirin placebo and Vitamin D active ingredient - Vigantol® Oil
Arm Title
Aspirin placebo, Vitamin D placebo
Arm Type
Experimental
Arm Description
Aspirin placebo and Vitamin D placebo - Miglyol®812 Oil
Intervention Type
Drug
Intervention Name(s)
High dose Aspirin & Vitamin D
Other Intervention Name(s)
Aspirin - acetylsalicylic acid, Vitamin D - Vigantol® Oil
Intervention Description
Aspirin 1 x 300mg tablet daily & Vitamin D 4,000IU daily. (8 drops).
Intervention Type
Drug
Intervention Name(s)
High dose Aspirin, Vitamin D placebo
Other Intervention Name(s)
Aspirin - acetylsalicylic acid, Vitamin D placebo - Miglyol®812 Oil
Intervention Description
Aspirin 1 x 300mg tablet daily & Vitamin D placebo (8 drops).
Intervention Type
Drug
Intervention Name(s)
Low dose Aspirin , Vitamin D
Other Intervention Name(s)
Aspirin - acetylsalicylic acid, Vitamin D - Vigantol® Oil
Intervention Description
Aspirin 1 x 100mg tablet daily & Vitamin D 4,000IU daily. (8 drops).
Intervention Type
Drug
Intervention Name(s)
Low dose Aspirin, Vitamin D placebo
Other Intervention Name(s)
Aspirin - acetylsalicylic acid, Vitamin D placebo - Miglyol®812 Oil
Intervention Description
Aspirin 1 x 100mg tablet daily & Vitamin D placebo 8 drops daily.
Intervention Type
Drug
Intervention Name(s)
Aspirin Placebo, Vitamin D
Other Intervention Name(s)
Vitamin D - Vigantol® Oil
Intervention Description
Aspirin 1 x 300mg placebo tablet daily & Vitamin D 4,000IU daily. (8 drops).
Intervention Type
Drug
Intervention Name(s)
Aspirin placebo, Vitamin D placebo
Other Intervention Name(s)
Aspirin Placebo, Vitamin D, Vitamin D placebo - Miglyol®812 Oil
Intervention Description
Aspirin 1 x 100mg placebo tablet daily & Vitamin D 4,000IU daily. (8 drops).
Primary Outcome Measure Information:
Title
Rate of Patient Recruitment to a Randomised Chemoprevention Study in Men Enrolled on an Active Surveillance Programme for Prostate Cancer. Number Accrued Per Month.
Description
The proportion of eligible patients that join the trial over the 12-month trial recruitment period.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
3 years
Title
Number of Participants With Biochemical (PSA) Disease Progression
Description
50% increase in serum Prostate Specific Antigen at 12 months from baseline.
Time Frame
12 months
Title
Number of Participants With Histological Disease Progression
Description
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)
Time Frame
3 years
Title
Number of Patients With Adverse With Toxicity, Allergy or Symptoms From Aspirin or Vitamin D
Description
Aspirin toxicity: Haemorrhagic stroke, anaphylaxis following administration, gastrointestinal bleeding requiring intervention (both medical and surgical) Vitamin D3 toxicity: Hypercalcaemia, Anaphylaxis
Time Frame
18 months + 30 days

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Greg Shaw, MD
Organizational Affiliation
Queen Mary London
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jack Cuzick, PhD
Organizational Affiliation
Queen Mary London
Official's Role
Study Director
Facility Information:
Facility Name
Darent Valley Hospital
City
Dartford
ZIP/Postal Code
DA2 8DA
Country
United Kingdom
Facility Name
University Hospital of Wales
City
London
ZIP/Postal Code
CF14 4XW
Country
United Kingdom
Facility Name
University Hospital UHCW NHS Trust
City
London
ZIP/Postal Code
CV2 2DX
Country
United Kingdom
Facility Name
St Bartholomews Hospital London, Bart's and the London school of Medicine
City
London
ZIP/Postal Code
EC1A 7BE
Country
United Kingdom
Facility Name
University College Hospital London
City
London
ZIP/Postal Code
NW1 2B
Country
United Kingdom
Facility Name
Homerton Hospital
City
London
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
ZIP/Postal Code
S016 6YD
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

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

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