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.
0
20
40
60
80
100
120
140
160
180
200
Patient
num
bers
Month
Actual recruitment per
month
Open sites
Active sites (KRAS or
randomising)
Actual cumulative
recruitment
0
10
20
30
40
50
60
70
Ma
r-…
Ap
r-0
9
Ma
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Jun
-09
Jul-
09
Au
g-…
Se
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9
Oc
t-0
9
No
v-…
De
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9
Jan
-10
Fe
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0
Ma
r-…
Ap
r-1
0
Ma
y-…
Jun
-10
Jul-
10
Au
g-…
Se
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0
Oc
t-1
0
No
v-…
De
c-1
0
Actual recruitment per month Open sites Target active sites
Actual active sites Actual cumulative recruitment
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: [email protected] 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: [email protected]
FIAT Trial Coordinator: Manjinder Kaur, Tel: 0121
415 9104; e-mail: [email protected]
FOxTROT Trial Administrator: Zoe Gray, Tel: 0121
415 9106; e-mail: [email protected]
Data Managers: Dominic Lancaster, e-mail:
[email protected]; Amy Peters,
e-mail:[email protected]
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!