PET-NECK: Setting Up A Collaborative Clinical Trial
In A Rare Disease Site
Janet Dunn, Claire Balmer, Chris McConkey, Chris Nutting, Sheila Fisher, Wai-lup Wong, Ken MaClennan, Chris
McCabe, Claire Hulme, Hisham Mehanna. Warwick Medical School Clinical Trials Unit, University of Warwick, UK
Background
Fig.2:
toinapprovals
TimeTime
to approval
site set-up
•PET-NECK is a national, multi-centre, randomized phase III trial comparing PETCT guided ‘watch and wait’ with planned neck dissection for the management of
locally advanced (N2/N3) nodal metastases in patients with head and neck
squamous cancer (Figure 1).
Grant activation to
ethical approval
•7,000 new Head & Neck Cancers (HNC) per year in the UK of which we estimate
30% will eventually be eligible for the trial.
Ethical approval to
R&D
25th percentile
Median
75th percentile
•HNC is treated at specialist centres of which there are around 20 in the UK.
•The UK has invested in the establishment of a National Cancer Research Network
who can provide support for National Cancer Research Network (NCRN) trials.
Grant activation to
ARSAC
•PET-NECK is currently the only phase III trial in the NCRN trials portfolio and is
compatible with commercial drug trials
Fig.1: PET-NECK Trial Design
R&D to open
Grant activation to
open
0
Randomise eligible patient with
MDM decision for concurrent CRT
Surveillance
(Experimental)
group
Standard
concomitant CRT
2
4
6
8
10
12
ND
(Control)
group
Fig.3: Overall recruitment
ND before
CRT
CT & Assessment
@ 9-13 wks after CRT
completion
Primary recurrence
or no CR to primary
CR and neck -ve
on PET-CT?
400
Planned
Actual
300
200
100
0
Refer to MDM for
consideration for
salvage surgery
CR, neck +ve or
equivocal on PET-CT?
560
500
CR and no primary
recurrence
Se
pD 07
ec
-0
M 7
ar
-0
Ju 8
nSe 08
pD 08
ec
-0
M 8
ar
-0
Ju 9
nSe 09
pD 09
ec
-0
M 9
ar
-1
Ju 0
nSe 10
p10
No CR to primary
N (Recruited)
600
PET-CT & Assessment
@ 9-13 wks after CRT
completion
14
Months
Key: ARSAC=Administration of Radioactive Substances Advisory Committee
R&D=Research and Development
Date
Neck
dissection
within 4 wks
Clinical Follow up:
yr 1- monthly; yr 2-twomonthly*
CRT: radical concurrent chemoradiotherapy
CR: complete response of primary site on post treatment assessment
ND: neck dissection (either modified or selective)
PET-CT: Positron Emission Tomography – Computerised tomography scan
Assessment - CT and/or MRI + Examination under anaesthetic (EUA) post completion of CRT
•Time to approval was slow for the first centres since they all had to wait for
initial ethics, R&D and ARSAC approval; subsequent centres have reduced
approval time (Figure 2).
•The trial involves many disciplines (e.g. surgery, medical oncology, clinical
oncology, radiology, pathology) extending the local R&D approval time.
• PET-CT scanning is a ‘new’ technology with the distribution of scanners
increasing rapidly. There remains a need for training and Quality Assurance.
•Recruitment will be on track at the end of the year; 29 sites (Figure 3).
Primary endpoints:
Overall Survival
Secondary endpoints:
Conclusions
•Disease specific survival
•Local control in neck
•Surgical complication rates
•Quality of life
•Healthcare economics
•Establishing a clinical trial in a rare cancer disease site with little preexisting infrastructure and involving new technology is challenging.
•Recruitment to this trial has started due to the persistence of the Trial
Centre, dedication of the Trials Team and the UK prioritisation of
Clinical Trials in the National Health Service.
•This trial serves an under represented group of people with cancer
and it remains imperative to continue to answer this important question
Milestones
•Funding awarded: 1st Apr 2007
Contact
•Approval in place at principal site: 1st June 2007
•Co-ordinator starts in post: 30th Aug 2007
•1st patient entered: 2nd Oct 2007
•Anticipated recruitment of 560 patients: Sept 2010
For more information please contact;
c.balmer@warwick.ac.uk
•We gratefully acknowledge the HTA for funding PET-NECK.