Merry Christmas and Happy New Year from the Coloproctology Trials Team at Birmingham

Clinical Trials Unit!

Welcome to the Christmas 2010 issue of the Coloproctology Trials newsletter from all at BCTU.

The coloproctology portfolio at BCTU includes FOxTROT, CReST, FIAT, TREC , PROSPER, QUASAR

and now also DREAMS.

Contents this Issue:

FOxTROT Phase III trial news

CReST Study update

FIAT trial opening to recruitment

TREC trial update

Thank you to everyone who has participated in our studies over this past year, both old collaborators and those new ones

joining us in 2010! We hope that you continue to support us and the coloproctology trials to help improve outcomes for

future patients. All of the trials in the coloproctology portfolio will only be a success through your wholehearted

support—so thank you for all of your time and efforts!

The FOxTROT Phase III Trial is now open to recruitment!

In September 2010 the phase II feasibility study of the FOxTROT trial was completed! Recruitment was on

target, with 150 patients randomised. The planned analysis of pilot data on the safety and feasibility of pre-

operative therapy and the accuracy of radiological staging demonstrated that pre-operative therapy is feasi-

ble, safe and well-tolerated. The data was also encouraging on the accuracy of radiological staging—it es-

tablished the accuracy of FOxTROT’s radiological eligibility criteria in identifying high-risk patients suit-

able for chemotherapy.

Based on the pilot study findings, we have implemented three protocol amendments for the phase III study:

1. Radiological eligibility has been widened to include all CT-staged T3 tumours. Our audit comparing

radiological and pathological staging found that just 9% of radiologically staged T3/T4 tumours were classi-

fied as low risk T2 on pathology, all of whom had received preoperative chemotherapy, this is likely attrib-

uted to downstaging by neoadjuvant treatment. Of 17 T3 tumours with invasion <5mm, only 1 was unsuit-

able for chemotherapy.

2. Introduction of FOxTROT lite – a shorter, 3 month course of chemotherapy for those patients for

whom 6 months is considered excessive.

3. Introduction of OxCap chemotherapy for those patients not randomised to receive panitumumab.

The BCTU Coloproctology Trials

Newsletter

December 2010

Open Centre Local PI Open Centre Local PI

1 Queen Elizabeth, Birmingham Dr Neil Steven 35 Musgrove Park Hospital Dr Julie Walther

2 Derriford Hospital Miss Clare Adams 36 The Whittington Hospital Dr Pauline Leonard

3 Royal Lancaster Hospital Dr David Eaton 37 Manchester Royal Infirmary Mr Jim Hill

4 Leeds General Hospital Prof Matt Seymour 38 The Christie Dr Mark Saunders

5 Queen Elizabeth, Gateshead Dr Werner Dobrowsky 39 Royal Liverpool Hospital Mr Paul Rooney

6 Huddersfield Royal Infirmary Dr Jo Dent 40 The Princess Alexandra Dr John Bridgewater

7 Sandwell General Hospital Mr Neil Cruickshank 41 Russells Hall Prof David Ferry

8 Charing Cross Hospital Dr Charles Lowdell 42 Castle Hill Dr Rajarshi Roy

9 Manor Hospital Dr Andrew Hartley 43 The Royal Marsden Hospital (Fulham) Prof David Cunningham

10 Maidstone District General Hospital Dr Mark Hill 44 The Royal Marsden Hospital (Sutton) Prof David Cunningham

11 Royal Bournemouth General Dr Tamas Hickish 45 Southampton General Hospital Dr Andrew Bateman

12 Poole General Hospital Dr Tamas Hickish 46 Barnsley District General Hospital Dr Debra Furniss

13 North Middlesex Hosptial Dr John Bridgewater 47 Royal Devon & Exeter Dr Melanie Osborne

14 Dorset County Hospital Dr Richard Osbourne 48 Heartlands Hospital Mr Charles Hendrickse

15 Mount Vernon Hospital Dr Rob Glynne-Jones 49 Hope, Salford Mr Nicholas Lees

16 Royal Free Hospital Dr Astrid Mayer 50 St George's Hospital Dr Fiona Lofts

17 Bristol Royal Infirmary Mr Mike Thomas 51 Queens Medical Centre Dr Vanessa Potter

18 Scunthorpe General Hospital Dr Abdel Hamid 52 Royal CornwallHospital Dr Richard Ellis

19 Diana Princess of Wales Dr Rajarshi Roy 53 New Cross Hospital Dr Simon Grummet

20 Queens Hospital (Romford) Dr Sherif Raouf 54 Good Hope Hospital Dr John Glaholm

21 Harrogate District Hospital Dr Kim Last 55 Queen Alexandra Hospital Dr Muthuramalingam

22 Leighton Hospital Dr Mike Braun 56 Ipswich Hospital Dr Rubin Soomal

23 West Middlesex Dr Rizvana Ahmad 57 Glan Clwyd Hospital Dr Simon Gollins

24 Basildon Hospital Dr David Tsang 58 North Hampshire& Basingstoke Dr Charlotte Rees

25 Southend Hospital Dr David Tsang 59 Arrowe Park/Clatterbridge Dr Nicholas Day

26 North Staffordshire Hospital Dr Fawzi Adab 60 Wythenshawe Hospital Dr Mike Braun

27 Northern Centre Cancer Treatment Dr Fareeda Coxon 61 Salisbury District Dr Tim Iveson

28 Southport & Ormskirk Hospital Dr Arthur Sun-Myint 62 York Hospital Dr Kim Last

29 Clatterbridge Oncology Centre Dr David Smith 63 Stepping Hill Hospital Dr Jurjees Hasan

30 Doncaster Royal Infirmary Dr Jonathon Wadsley 64 South Tyneside District General Dr Ashraf Azzabi

31 Wexham Park Hospital Dr Marcia Hall 65 Mid-Yorks NHS Trust Dr Daniel Swinson

32 Weston Park Hospital Dr Joanna Hornbuckle 66 Royal Preston/Sharoe Green Hospital Mr Nigel Scott

33 Bradford Royal Infirmary Dr Andy Conn 67 Chesterfield Royal Hospital Dr Debra Furniss

34 Frenchay & Southmead Hospitals Dr Kirsten Hopkins 68 City Hospital, Birmingham Mr Neil Cruickshank

FOxTROT Recruitment

With the implementation of the FOxTROT

protocol amendment across almost 90% of our

sites, we have already started to see an increase in

recruitment! December 2010 was the best recruit-

ing month so far with 12 patients randomised!

A big thank you to all of our sites who have

randomised a patient.

FOxTROT Top Recruiters

The top three recruiting sites in FOxTROT are:

1st University Hospital North Staffs

2nd Sandwell General Hospital

3rd St James’s University Hospital, Leeds

Thank you & well done to the teams at those sites!

KRAS testing in FOxTROT

An assessment of KRAS testing in the pilot trial

was also very encouraging—it showed that the

average time to result is approximately 7 days

from date of KRAS consent & that KRAS testing

was successful in over 95% of those patients who

consented to testing.

The centres that are currently participating in the FOxTROT trial are listed below.

Congratulations to the sites highlighted in red—all have already randomised at least 1 patient!

FOxTROT Publications

FOxTROT was presented at the new ―Trials in Progress‖

session at ASCO and generated a great deal of interest

from international sites. The radiological audit has also

just been accepted by Colorectal Disease! Please see the

back page for all publications.

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Open Centres Open Centres Local PI Local PI 1 Addenbrooke's Hospital 21 Northwick Park Hospital/ St Marks Nicola Fearnhead Arun Gupta

2 Bradford Royal Infirmary 22 Mid Yorks (Pinderfields / Dewsbury) Clive Kay Christopher Macklin

3 Darent Valley Hospital 23 Newcastle (Freeman Hospital) Michael Parker Barry Applpeton

4 Derby City General Hospital 24 Queen Elizabeth – Birmingham Ranjeev Singh Colm Forde

5 Derriford Hospital 25 Queen Elizabeth – Gateshead Clare Adams Mark Katory

6 Gartnavel Hospital 26 Raigmore Hospital Sivanathan Chandramohan Angus J M Watson

7 Glasgow Royal Infirmary 27 Royal Albert Edward Infirmary S Chandramohan Marius Paraoan

8 Harrogate District Hospital 28 Royal Cornwall Hospital David Leinhardt William Faux 9 Imperial College Hospital 29 Royal Devon & Exeter Peter Dawson Patricia Boorman

10 John Radcliffe Hospital 30 Russells Hall Hospital Raman Uberoi Sauid Ishaq

11 Kings College Hospital 31 Salisbury District Suzanne Ryan Simon Sleight

12 Leeds General Hospital 32 Salford Royal Hospital Damian Tolan Nicholas Lees

13 Leicester General / Royal Infirmary 33 Scarborough General Hospital Baljit Singh Ian Renwick

14 Leighton Hospital 34 Scunthorpe General Hospital Chelliah Selvasekar Syed Ahmed

15 Manchester Royal Infirmary 35 The Royal Bolton Hospital Jim Hill Anthony Maxwell

16 Neville Hall Hospital 36 Southmead/Frenchay (North Bristol) Nick Cross Anne Pullyblank

17 North Devon District Hospital 37 University Hospital Of North Durham Mark Cartmell Jagmohan Varma

18 North Manchester General Hospital 38 Western General Hospital Richard Hammonds Hugh Paterson

19 North Tees and Hartlepool 39 Whipps Cross University Hospital Talvinder Gill Pasquale Giordano

20 Northern General Hospital 40 Yeovil District Hospital Steven Brown Jonathan Ockrim

The CReST Trial

The CReST trial aims to establish whether endoluminal stenting is more effective for patients presenting with

obstructing colorectal cancer compared to emergency surgery and, if such a benefit exists, is this identifiable in

patients undergoing attempted curative treatment, palliative treatment, or both?

Over 70 patients now randomised

into CReST!

Recruitment to CReST is gathering momentum!

We now have 40 sites open to recruitment and

over 70 patients randomised! Thank you to all

sites which have randomised a patient!

And congratulations & thank you to the teams

at Manchester Royal Infirmary and Leeds

General Infirmary—who are joint first in our

recruitment table!

With plans to open CReST at a further 15 UK

hospitals and also to open internationally in

2011, we’re looking forward to an even greater

upturn in recruitment!

The CReST Trial at ACPGBI At ACPGBI in June this year, the CReST Chief Investiga-

tor, Mr Jim Hill, presented an update on the study and dis-

cussed how the CReST Data Monitoring & Ethics Commit-

tee had recently met and agreed that there were no concerns

with the stent success rate in the trial. There was a general

agreement that the failure of the Dutch stenting study high-

lights the importance of CReST and the need to reliably es-

tablish the benefits and risks of stenting before adoption of

the technique into routine practice.

New Stent Suppliers in CReST! We now have even more approved stent suppliers in

the CReST trial!

Recently 3 additional suppliers have joined the trial:

Cook Medical; BVM Medical and (in Jan 2011)

Diagmed will also be an approved supplier! Stents

can also be purchased from Pyramed, ConMed and

Boston Scientific.

Please remember though that you should contact the

trials office if you wish to use stents from another

supplier!

The Fistula-In-Ano Trial

The Fistula-In-Ano Trial comparing Biodesign® Surgisis® anal fistula

plug versus surgeon’s preference for transsphincteric fistula-in-ano.

Status Update:

The FIAT Chief Investigator is Mr David Jayne who is based at Leeds General Infirmary. FIAT is funded by

the NIHR Health Technology Assessment Programme and has ethical approval in place.

The first FIAT centre, Leeds General Infirmary, opened to recruitment in November 2010 and we are expect-

ing to recruit our first patient into the trial any day now! There are 74 centres across the UK that are currently

gaining the approvals necessary to take part in FIAT.

Trial Design:

Patients with a confirmed high transsphincteric fistula at

risk of incontinence with fistulotomy (involving ap-

proximately 1/3 or more of the external sphincter com-

plex), will be randomised between insertion of the

Biodesign® Surgisis® fistula plug and the surgeon’s

preference of advancement flap, cutting seton or fistu-

lotomy.

Trial Aims & Objectives:

FIAT aims to recruit 500 patients over 3 years.

Primary Objectives:

To assess if the anal fistula plug improves symptom

-specific quality of life

Secondary Objectives are to assess:

If the plug improves fistula healing rates

If there is an improvement in faecal continence

If there is a reduction in re-intervention rates

The nature and frequency of complications

The cost-effectiveness of the plug

EUA: High transsphincteric fistula ≥ 1/3

of sphincter complex

Insertion of draining seton

MRI fistulography

RANDOMISE

Fistula Plug

Insertion

Surgeons

Preference

Advancement Flap

Cutting Seton

Fistulotomy

Surgical & Radiology Workshops:

The 3rd Radiology workshop was held on the 19th Octo-

ber 2010, in Leeds and was a great success with 19 Radi-

ologists attending.

The 3rd Surgeons workshop is to be held on the 19th

January 2011, in Birmingham. Places are still available,

but filling up fast.

We now have a combined total of over 100 trained Sur-

geons and Radiologists!

Please contact the FIAT Study Office should you wish to

attend the upcoming FIAT Surgeons workshop.

Please note, it is a prerequisite for Local Principal Inves-

tigators to attend the workshops.

Plug Supply for the trial:

Plugs will be supplied free of charge for trial par-

ticipants. At site set-up, each centre will receive

an initial supply of plugs, re-supply will be man-

aged by the FIAT Study Office.

Upcoming Meetings:

The 3rd Surgeons workshop is to be held on the

19th January 2011, in Birmingham.

Contact the FIAT Study office to reserve your

place.

The FIAT Trial is now open to recruitment!

Centre Local PI

1 Clatterbridge Centre for Oncology Arthur Sun Myint

2 Good Hope Hospital Stephan Korsgen

3 John Radcliffe Hospital Neil Mortensen / Chris Cunningham

4 Manchester Royal Infirmary Jim HIll

5 Queens Medical Centre John Scholefield / Nick Armitage

6 St. Richards Jay Simson

7 St James University Hospital David Sebag-Montefiore

8 University Hospital, Birmingham Simon Bach

The TREC Trial Transanal Endoscopic Microsurgery (TEM) and Radiotherapy in Early Rectal Cancer

The TREC Trial has received ethical

approval!

The TREC trial has been funded by a grant from Can-

cer Research UK and now has ethical approval in

place!

The study is due to open to recruitment in early 2011!

Study Design

The TREC trial is a randomised, phase II feasibility

study comparing conventional TME surgery with

short course preoperative radiotherapy (SCPRT) and

delayed local excision with TEM (after an 8-10 week

interval) for patients with early (T1 or T2 N0) rectal

cancer as defined according to MRI & ERUS.

Study Objectives

The TREC trial pilot study aims to assess the feasibil-

ity and inform the design of a large, multi-centre

RCT. The data collected in the TREC pilot study will

allow accurate sample size estimation and will allow

refinement of primary outcome measures for the

Phase III TREC trial.

The primary objective in TREC is RECRUITMENT.

Secondary objectives will be i) Safety of SCPRT and

delayed local excision ii) Efficacy of the novel treat-

ment in producing tumour downstaging and iii)

Acceptability of randomisation for clinicians and pa-

tients.

TREC aims to randomise 46 patients over 2 years.

How To Get Involved:

If you would like to get involved in the TREC trial

then please contact the TREC office:

E-mail: e.l.magill@bham.ac.uk Tel: 0121 415 9105

TELEPHONE RANDOMISATION WILL CLOSE AT

12.00pm ON 23rd DECEMBER AND REOPEN AT

9am ON 5th JANUARY.

For CReST Trial Randomisations over this period,

please log on to: www.trials.bham.ac.uk/CReST

From December 14th until Jan 5th please send blocks

for KRAS testing to: Dr Philippe Taniere FOxTROT Trial Laboratory

Department of Cellular Pathology, Level –1

QE Hospital Birmingham, Mindelsohn Way Edgbaston, Birmingham, B15 2WB

RANDOMISATIONS AND CONTACTS OVER THE CHRISTMAS PERIOD

For urgent FOxTROT Clinical Queries, please

contact the FOxTROT Chief Investigator, Professor

Dion Morton on: 07530 593 885

For urgent CReST clinical queries, please contact

the CReST Chief Investigator, Mr Jim Hill, on:

07545193094

For randomisation queries for both FOxTROT and

CReST, please contact the Coloproctology Trials

Manager, Dr Laura Magill on 07966098477.

The DREAMS Trial—Dexamethasone Reduces

Emesis After Major Colorectal Surgery

Publications

The Coloproctology Team At BCTU

Coloproctology Trials Team Leader: Dr Laura Magill,

Tel: 0121 415 9105; e-mail: e.l.magill@bham.ac.uk

FIAT Trial Coordinator: Manjinder Kaur, Tel: 0121

415 9104; e-mail: m.kaur@bham.ac.uk

FOxTROT Trial Administrator: Zoe Gray, Tel: 0121

415 9106; e-mail: z.b.gray@bham.ac.uk

Data Managers: Dominic Lancaster, e-mail:

d.lancaster@bham.ac.uk; Amy Peters,

e-mail:a.c.peters@bham.ac.uk

1. Dighe S, Swift I, Magill L, Handley K, Gray R, Quirke P, Morton D, Seymour M, Warren B, Brown G. Accuracy of

radiological staging in identifying high-risk colon cancer patients suitable for neoadjuvant chemotherapy – multicentre

experience. Accepted by Colorectal Disease

2. Magill L, Gray R, Morton D, Brown G, Ferry D, Handley K, Quirke P, Seymour M, Warren B for the FOxTROT Col-

laborative Group. FOxTROT: randomised phase II/III study of neoadjuvant chemotherapy ± an anti-EGFR monoclonal

antibody for locally advanced, operable colon cancer. Poster presentation, NCRI Annual Meeting 2010.

3. Morton D, Brown G, Ferry D, Gray R, Magill L, Quirke P, Seymour M, Warren B for the FOxTROT Collaborative

Group. FOxTROT: randomised phase 2 study of neoadjuvant chemotherapy (CT) ± an anti-EGFR monoclonal antibody

for locally advanced, operable colon cancer. JCO, 2010 ASCO Annual Meeting Proceedings (Post-Meeting Edition) Vol

28, No 15_suppl (May 20 Supplement), 2010: TPS192

The DREAMS Trial has just been funded by a

grant from Bowel Disease Research Foundation!

The DREAMS trial is a phase III, double blind, ran-

domised controlled trial investigating the effects of a

single dose of 8mg IV dexamethasone on patient re-

covery after colorectal surgery.

The study is the first RCT of an Investigational Me-

dicinal product to be developed by the surgical

trainee-led West Midlands Research Collaborative

and the Birmingham Clinical Trials Unit.

Trial Objectives

Primary objective—To determine if preoperative

dexamethasone reduces post-operative nausea &

vomiting in patients undergoing elective colorectal

resections.

Secondary objectives—To determine if there are

measurable benefits during recovery from surgery

with the use of dexamethasone, benefits investigated

will include quicker return to oral diet and reduced

length of hospital stay.

Trial Current Status:

DREAMS has received funding from BDRF and now

has ethical approval in place! The MHRA opinion is

expected before Christmas. Nine sites have already

signed up to participate and we aim to open to recruit-

ment in Feb 2011.

If you would like to get involved, then please contact a

member of the coloproctology team!