Pomi-T study design

Recruitment and progress:

Completed 10 months ahead of schedule! Total number recruited 203 men. Trial results presented at ASCO 2013.

Scientific question:

Does supplementing the diet with an anti-oxidant and polyphenol rich food supplement have an affect on the rate of PSA progression in men with prostate cancer managed by active surveillance?

Principal Investigator:

Professor Robert Thomas MRCP MD FRCR 
Consultant Oncologist, Cranfield University, Bedford & Addenbrooke’s, NHS Hospital Trusts. .

News:

In view of the the enthusiastic and rapid recruitment, following an further review by the UK ethics committee, the trial numbers have been increased to 200. Also in view of the good tolerance of the intervention, the ethics committee has agreed that participants can take 3 tables a day.

Accrual to date and timelines:

This study was developed with the help of the National Cancer Research Institute Complementary Therapies Clinical studies Design Group.
National Research Ethics (NREC) approval was granted in October 2011. National trials number 11/EE/0314.
This trial has now been adopted and supported by the UK National Cancer Research Network NCRN

Financial sponsors:

The trial was funded from an unrestricted educational grant awarded by the charity - Prostate Action

Background to the study:

This scientifically robust study aims to establish whether boosting the diet with a food supplement rich in plant chemicals (polyphenols) which have antioxidant and other potential anti-cancer properties has an influence on PSA progression compared to placebo.

Epidemiological and large cohort studies support the paradigm that antioxidant-rich diets reduce the risk of prostate cancer (Giovannucci et al 2002). More recently prospective studies show that diet and lifestyle may also benefit men with established disease by slowing or halting PSA progression (Ornish 2005, Thomas 2008). A review of the international literature has highlighted green tea, pomegranate, broccoli and curcumin as those with some of the best evidence for a positive affect on PSA (Thomas et al 2011). These studies, however, have involved small numbers of participants, not been randomised, or placebo controlled and hence are not regarded as scientifically vigorous but despite this, up to 70% of men have been reported to take some form of nutritional supplement after a diagnosis of prostate cancer.

To answer the question of whether food supplements are a helpful addition to the diet of men with prostate cancer, this trial has been designed to the highest possible scientific statistically valid standards. If the supplement is proven to be beneficial, then up to a third of men with prostate cancer will benefit from a simple dietary manipulation which could potentially delay or prevent the progression to more radical interventions with their associated toxicities.

The four foods within Pomi-T® ( green tea | broccoli | pomegranate | turmeric) are thought to have a variety anti-cancer properties; promoting differentiation (slowing cellular growth), encouraging apoptosis (encouraging cells to die when they have reached the end of their natural cycle) and preventing further DNA damage via the antioxidant process (absorbing the super-oxide free radicals produced from our environment ). By protecting the prostate cancer cells from further genetic damage it is hoped that indolent malignant or pre-malignant cells do not progress into more aggressive types. The rationale for combining four different whole foods types (berry, vegetable, spice and leaf) was to provide a wide spectrum of natural polyphenols, avoiding over-consumption of one particular type.

Pomi-T® is made by a UK supplement manufacturer Power Heath Products Ltd, Pocklington, York YO42 1NR. It is supplied to the trial centres in blank bottles together with an identical placebo pills. The trial centres are unable to supply the supplement to participants outside the trial. Furthermore, during or even after the trial has finished Pomi-T® will not be able to be prescribed by a doctor because it is classed as a food not a drug. The committee of this trial as advised that we sign post where individuals can find more information on Pomi-T® - this is via a web site called www.pomi-t.com. The trial centre has no legal or official connection to suppliers of Pomi-T® outside the parameters of this study .

Methodology

A double blind placebo controlled randomised trial. Following written informed consent, 200 men will be randomised between food supplement versus placebo (2:1).  After trial entry they are given 3 months supply of investigational product labeled either A or B. They are reviewed at 3 months. If at that point it is appropriate to continue active surveillance they are given a further three months product. At six months the trial ends.

Randomisation
2:1
Pomi-t
1 tab bd
6 monthsPlacebo
1 tab bd

Eligibility

Men with histologically confirmed carcinoma of the prostate managed with active surveillance or experiencing a significant PSA relapse post radiotherapy deems not suitable for salvage surgery

Trial end points and safety meausers:

Trial end points will be measured at entry (baseline), 3 months and 6 months

Primary:

  • Median PSA raise between the two randomised groups

Secondary:

  • Number remaining on active surveillance at three and six months
  • Cholesterol
  • Blood Sugar
  • C-reactive protein
  • Blood pressure
  • A retrospective analysis of the prospective data was performed on the prostate MRI images

Safety measures:

  • LFT's
  • U&E's
  • CRF record of any symptom relating to toxicity and tolerance
  • A retrospective analysis of testosterone levels was preformed after the final analysis

Trial approval and regulations:

The trial has been designed with the help of senior statisticians from Cranfield University, patient survivors, senior oncologist, urologists, nutritionalists and was adopted by the National Cancer Research Institute Complementary Medicines Committee. It was approved by the National Ethics committee. The Medicines and Health Regulatory Agency have has formally notified the Chief investigator that no MHRA licence is required on the grounds that Pomi-T® is a food supplement not a prescribed drug. Pomi-T®, and the placebo is made a well established UK manufacturer complying to European Food Standards quality controls.

Trial quality assurance

The design and implementation of this study has adhered strictly to European standards of "Good Clinic Practice" Guidance (GCP). The trial members all have up to date certificates. An external, independent trials auditor has assessed the trial processes at the commencement of the study and will assess the blindness of the locked databases prior to statistical analysis. A separate independent audit of trial and data compliance conducted at the end of the study.

Trial development committee:

Pat Bellamy - Statistician, Cranfield University.
Mr Michael Vogel - Patient representative
Mike Hollingworth - Patient Representative and Chairman, PCaSO Prostate Cancer Network 
Alasdair MacSween - Principal Lecturer in Research Governance, Chair of School of Health & Social Care Research Ethics Committee 
Sharon Love - Senior Statistician and Head of CR-UK Statistical Support, Centre for Statistics in Medicine, Oxford
Harbinda Sharma - Consultant Urologist Bedford Hospital
Cathryn Woodward - Consultant Oncologist Addenbrooke’s and Bury St Edmonds 
Anne Willis - Trials Nurse Bedford Hospital

Trial manager:

Madeleine Williams
Research Manager
Primrose Oncology Research Unit

Trial sponsor:

Dr Jeremy Sizer
Head of R&D, Bedford Hospital
Bedford MK42 9DJ, Tel: 01234 792274

Randomisation process:

The placebo and supplement have an identical appearance and have identical packaging. The allocation of A or B was determined by an individual independent of the trials unit and this information placed in an opaque envelop closed with sealing wax. The envelopes were likewise produced by the responsible individual not attached to the trials unit with A or B stuck onto thick opaque cards and placed into an obaque envelopes again sealed with sealing wax. As added protect of bias avoidance, the patient themselves selects an envelope form the box. This process ensured the physicians, trial staff and patients were blind to the ingredients throughout the duration of the study. Secondly, the statistician, who is independent and remote from the trial centre, will not be given the codes for blinding and will not have encountered patient or trial medication (A or B) for the duration of the study. This ensures the statistical evaluation is also blind. Finally, an independent clinical trials auditor reviewed the trials process to ensure it was compliant with the European trial directive.

Co-ordinating centre:

The Primrose Unit, Bedford Hospital, Bedford MK42 9DJ. Tel: 44 (0) 1234 795 787, Fax: 44 (0) 1234 792 668,

Pomi-T® is manufactured in the UK, from natural ingredients, to the highest quality assurance standards and EU compliance regulations by powerhealth Ltd. Pomi-T is owned by natureMedical Products. Website: Email: support@pomi-t.com. It was supplied to the trial centres in blank sealed bottles together with an identical placebo pills. The trials centre commissions an indepedent analysis on the authenticity of ingredients as part of its quality control requirementsThe trial centres are unable to supply the supplement to participants outside the trial. Furthermore, during or even after the trial has finished Pomi-T® will not be able to be prescribed by a doctor because it is classed as a food not a drug. The committee of this trial as advised that we signpost where individuals can find more information on Pomi-T® - this is via the web site www.Pomi-T.com. The trial centres has no legal or official connection to suppliers of Pomi-T® outside the parameters of this study .