Anal Cancer Trial Umbrella Personalising Radiotherapy Dose in Anal Cancer including ACT3 and ACT4 trials
Study Team including specific leads
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Lead – David Sebag-Montefiore ACT3 trial leads – Mark Harrison Richard Adams ACT4 trial leads – Maria Hawkins David Sebag-Montefiore Non trial IMRT lead – Rebecca Muirhead Imaging – Vicky Goh Medical Oncology – Sheela Rao Pathology – Gordon Hutchins Local excision lead – Andrew Renehan Patient and Public Involvement – Lindy Berkman, Alf Oliver Translational leads – Duncan Gilbert and Andrew Renehan RTQA – Liz Miles PROMS – Galina Velikova and Alex Gilbert IRCI - Rob Glynne-Jones USA Task Force/Intergroups – Lisa Kachnic Clinical Nurse Specialist – Gillian Knowles Clinical Trial Unit – Leeds – Alex Smith, Walter Gregory, Lucy McParland
Background • 3 phase III trials defined MMC 5FU CRT as standard of care • • •
ACT1 (UKCCCR) RT vs CRT (wide field RT + gap + boost) EORTC trial as per ACT1 RTOG 5FU RT +/- MMC
• 3 further phase 3 trials • • •
ACT2 n=940 2 phase RT technique no boost no gap • No benefit for maintenance Cis 5FU (ACT2) • No improvement in CR with concurrent cisplatin vs 5FU RTOG 9811 • Inferior outcome with neoadjuvant + conc Cis 5FU (RTOG 9811) ACCORD 03 • No benefit for neoadjuvant Cis5FU • “Signal” of benefit for sequential boost after a gap (standard vs higher dose)
• Targeted (EGFR) not encouraging
Background • Previously “one dose fits all” • The gap does not make radiobiological sense • IMRT can reduce acute toxicity – RTOG 0529 phase II (Kachnic et al) – UK solution developed (Muirhead et al NCRI 2013) • Translate ACT2 doses into singe phase IMRT • Adapt target volume atlases • Define standard doses for future control arms • Multicentre solution • IMRT allows SIB dose escalation • No prolongation in overall time • RCR audit (Q4 2014)
Scientific Question and portfolio fit • The scientific question – Personalised radiotherapy dose for patients with anal cancer – TRIALS – ACT3 – dose de-escalation for early stage disease – ACT 4 – dose escalation for locally advanced disease – Evaluate IMRT outcomes for anal cancer (“Standard” cohort) – Evaluate outcomes after local excision (“Local excision” cohort) – Anal cancer platform for translational (imaging and biomarker) research
• Portfolio fit and CSG discussion – – – – –
UK is at the international forefront for anal cancer trials (ACT1 and ACT2) Developed with and by the ano-rectal subgroup of the Colorectal CSG No competing trials in the UK No phase III trials in progress worldwide Presented and supported by the anal cancer IRCI group
• Patient and Public Involvement – Lindy Berkman, Alf Oliver and Pelvic Radiation Disease Association
The “Umbrella” ?International trial T1 N0 Anal margin Local excision
