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
Imaging		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: [email protected]