PLATO

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

Anal cancer is a rare disease, but its incidence is rising rapidly. Approximately 1000 cases in the UK and 5,000 in the USA are diagnosed each year. Standard treatment for anal cancer includes concurrent Mitomycin C, 5-Fluorouracil and radiotherapy, and more recently, concurrent Mitomycin C, capecitabine and radiotherapy. A new generation of clinical trials is now required that optimises radiotherapy dose based on stratified risk assessment.

PLATO is an integrated protocol, comprising 3 separate trials: ACT3, ACT4 and ACT5 funded by Cancer Research UK and led by Professor David Sebag-Montefiore from Leeds.

 

ACT3

ACT4

ACT5

Population

Invasive primary squamous cell carcinoma of the anus

 

T1N0 or Nx anal  margin tumour treated with local excision

T1-2≤4cm, N0 or Nx anal canal

T2≤4cm N0 or Nx anal margin

T2, N1-3 or T3-4, Nany anal canal or margin

Design

Non-randomised Phase II trial

Randomised Phase II trial

Randomised seamless pilot/Phase II (3-arm)/Phase III (2-arm) trial

Sample size

n=90 over 3 years

n=162 over 2 years

n=677 over 5 years

Aim

To determine whether a strategy of local excision where patients with ≤1mm margins receive additional radiotherapy with chemotherapy results in low rates of locoregional failure

To determine whether in early stage cancer radiotherapy dose de-escalation with chemotherapy results in acceptably low rates of locoregional failure and reduced acute & late toxicity

To determine whether in locally advanced cancer radiotherapy dose escalation with chemotherapy reduces the proportion of locoregional failure with acceptable acute & late toxicity

Primary objective

To assess the 3-year locoregional failure rate in participants

To assess the 3-year locoregional failure rate in participants

To assess the 3-year locoregional failure rate and time to failure in participants

Imaging assessment:

Imaging

 

Post therapy

Baseline

3-months

6-months

12-months

24-months

36-months

ACT 3

MRI

+

 

 

+

+

 

ACT 4

MRI

+

+

+

 

 

 

CT

+

 

 

+

+

+

PET/CT*

+

 

 

 

 

 

ACT 5

MRI

+

+

+

 

 

 

CT

+

 

 

+

+

+

PET/CT*

+

 

 

 

 

 

*strongly recommended

Enquires should be directed to:

PLATO study team, Leeds Clinical Trials Unit

Email: plato@leeds.ac.uk