PLATO

PersonaLising Anal cancer radioTherapy dOse – Incorporating ACT3, ACT4 and ACT5

Logos for the PLATO trial, Cancer Research UK and Stand up to cancer

PLATO is an integrated protocol, comprising 3 separate non-CTIMP trials (ACT3, ACT4 and ACT5) which aims to optimise radiotherapy dose (in combination with chemotherapy) (CRT) for low-, intermediate- and high-risk anal cancer. 

Trial status: Open

Chief Investigator: Professor David Sebag-Montefiore, St James’s University Hospital, Leeds and University of Leeds

Trial Co-Leads:
Professor David Sebag-Montefiore, Leeds (ACT5)
Professor Maria Hawkins, Oxford (ACT5)
Dr Richard Adams, Cardiff (ACT4)
Dr Mark Harrison, Mount Vernon (ACT4)
Professor Andrew Renehan, Manchester (ACT3)
Dr Rebecca Muirhead, Oxford (ACT3)

ISRCTN: ISRCTN88455282

Trial Contact:
Dr Sue Bell, Senior Trial Manager
Tel: 0113 343 1492
plato@leeds.ac.uk


 ACT 3
 ACT 4
  ACT 5
Population

Invasive primary squamous cell carcinoma of the of the anus:
T1 N0 or Nx anal margin tumour treated with local excision
T1-2 ≤4cm N0 anal canal, or
T1-2 ≤4cm Nx anal canal, or
T2 ≤4cm N0 anal margin, or
T2 ≤4cm Nx anal margin

T2 N1-3, or
T3-4 N any
Anal margin or canal
Design
Non-randomised phase II trial
Randomised phase II trial
Randomised seamless pilot / phase II (3-arm) / phase III (2-arm) trial
Research Questions
For small anal margin lesions treatable by local excision, does highly selective lower-dose CRT result in low rate of locoregional failure (LRF)?
For early stage disease, does lower dose CRT result in an acceptably low rate of LRF and reduced acute and late toxicity?
For locally advanced anal cancer, does dose-escalated CRT using IMRT result in a significant reduction in LRF with acceptable acute and late toxicity?
Intervention
Observation (margin >1mm)
or
41.4Gy 23F & Mitomycin C and capecitabine (margin ≤1mm)

Non-randomised

50.4Gy 28F & Mitomycin C and capecitabine
vs
41.4Gy 23F & Mitomycin C and capecitabine

1:2 randomisation ratio
53.2Gy 28F & Mitomycin C and 5FU or capecitabine
vs
58.8Gy 28F & Mitomycin C and 5FU or capecitabine
vs
61.6Gy 28F & Mitomycin C and 5FU or capecitabine

1:1:1 randomisation ratio

No elective nodal irradiation With elective nodal irradiation With elective nodal irradiation
Sample size 90 patients over 3 years 162 patients over 2 years 640 patients over 5 years
Pilot phase n=60
Phase II n= 80
Phase III n=500
Follow-up All participants will be followed up at 6 weeks post-end of treatment, 3-monthly in Years 1-2, 6-monthly in Year 3, then annually until 3 years post close of recruitment (or death). Survival outcomes beyond this time will be obtained from the National Cancer Data Repository (NCDR).
Primary endpoint
• Locoregional failure (LRF) at 3 years
Secondary endpoints • Acute and late toxicities
• Treatment compliance
• Clinical response rate (cRR)
• Disease-free survival (DFS)
• Colostomy-free survival (CFS)
• Progression-free survival (PFS)
• Overall survival (OS)
• Patient Reported Outcome Measures (PROMs)

Diagram showing the PLATO trial process