IP4- CHRONOS is open! CHRONOS is a phase II randomised control trial, that will review the outcomes (including oncological, functional, quality of life and cost-effectiveness) of focal therapy against those from radical therapy, in men with newly diagnosed localised clinically significant prostate cancer.
All men newly diagnosed with low-intermediate risk prostate cancer, confined to the prostate, with a life expectancy of at least 10 years will be screened for eligibility. Men must be well enough to undergo the interventions outlined in the trial prior to being enrolled.
Men will then have a choice of enrolling into CHRONOS A or CHRONOS B. CHRONOS A will randomise men to having radical whole gland treatment (radiotherapy, brachytherapy or prostatectomy), or focal therapy (HIFU or cryotherapy). CHRONOS A will answer the question, ‘is focal therapy equivalent in cancer control as radical therapy?’ CHRONOS B will randomise men to having focal therapy with or without additional neoadjuvant treatment and will answer the question: ‘can the success of focal therapy be improved by using neoadjuvant treatment?’ Randomisation will be stratified by disease characteristics.
All men will undergo intervention as they would within the NHS, however by doing so in a trial setting, we can directly compare the results of such treatments against each other. As the follow up mimics that of standard of care, the extra burden of treatment within the trial is minimal.
60 men will be recruited into both CHRONOS A and CHRONOS B (total 120) over a 1-year period, during the pilot, and if recruitment is successful the aim is to continue to a larger study assessing 2450 patients over 5 years, with a minimum follow up of 3 years. The primary outcome measures will be progression free survival in CHRONOS A, and failure free survival in CHRONOS B. The CHRONOS pilot will open in 12 UK hospital sites, aiming to open across the UK and Europe within the larger study.
CHRONOS is entirely funded by the Prostate Cancer UK charity, and available on the NIHR CRN portfolio. If you would like to join the main phase of CHRONOS as a site, please contact Miss Deepika Reddy ([email protected]) or visit our website for further information www.imperialprostate.org.uk/CHRONOS
Prof Hashim U. Ahmed (CHRONOS PI&CI)
Mr Taimur T. Shah (CHRONOS sub-investigator, Urology SpR & Research Fellow)
Miss Deepika Reddy (CHRONOS Clinical Research Fellow)
IP2 – ATLANTA is launched! ATLANTA is a phase II randomised controlled trial that will explore sequential multi-modal treatment using systemic therapy, local physical cytoreduction and metastasis directed therapy in men with newly diagnosed metastatic prostate cancer against a comparator of standard of care alone.
All men with new histologically diagnosed hormone sensitive metastatic prostate cancer, within three months of commencing androgen deprivation therapy (ADT), and of performance status 0 to 2 are eligible. No upper limit on metastatic burden will apply, although men must be fit to undergo all trial interventions at point of randomisation.
Men will be randomised to: Control (Standard of Care) OR Intervention 1 (Minimally Invasive Ablative Therapy [MIAT] +/- pelvic lymph node dissection [PLND]) OR Intervention 2 (Local Radiotherapy +/- Lymph Nodes OR Radical Prostatectomy +/- PLND). Randomisation stratified by metastatic burden (CHAARTED definition), intent to treat pelvic lymph nodes, intent to treat metastasis and intent to commence chemotherapy.
Systemic therapy in all arms includes ADT +/- Docetaxel. Radical prostatectomy will be with or without PLND. Local radiotherapy will be 60Gy/20Fr OR 74-78Gy in 2Gy per fraction over a minimum of 27 days, with or without simultaneous nodal radiotherapy. MIAT will be cryotherapy or focal HIFU. Men in both intervention arms will be eligible for metastasis directed therapy in the form of stereotactic ablative radiation (SABR) or surgery.
Men will be recruited over a two year period and followed up for a minimum of two years. Primary outcome will be progression free survival (PFS). ATLANTA is commencing in 17 UK trial centres with a target recruitment of 80 patients in the internal pilot, rising to 918 patients in full phase across 30 UK trial centres from November 2019.
ATLANTA is entirely charity funded (Wellcome Trust) and available on the NIHR CRN portfolio. Follow-up trial visits are not in excess of routine practice and extra burden is minimal. If you would like to join the main phase of ATLANTA as a site, please contact Mr Martin J. Connor ([email protected]) www.imperialprostate.org.uk/ATLANTA.
Prof. Hashim U. Ahmed (ATLANTA PI & CI),
Mr. Martin J. Connor (ATLANTA Doctoral Clinical Research Fellow)
Mr. Taimur T. Shah (Urology SpR & Research Fellow)
ATLANTA Surgeons Board: Mr Mathias Winkler, Mr Tim Dudderidge, Prof. Chris Eden, Mr Paul Cathcart, Prof. Naeem Soomro, Mr Adel Makar
ATLANTA Radiotherapy Board: Prof. John Staffurth, Dr. Alison Falconer, Dr. Stephen Mangar, Dr Olivia Naismith, RTTQA team
ATLANTA MIAT Board: Prof. Hashim U. Ahmed, Mr Stuart McCracken, Mr Raj Nigam, Mr Tim Dudderidge, Prof Iqbal Shergill
ATLANTA SABR Board: Dr Vincent Khoo, RTTQA team
ATLANTA Medical Oncologists: Dr. Naveed Sarwar, Dr Michael Gonzalez
ATLANTA Trial Sites: Imperial College Healthcare NHS Trust, The Royal Marsden Hospital, Guy’s & St Thomas’ NHS Foundation Trust, London North West Healthcare NHS Trust, Royal Surrey County (Guildford) Hospital, University Hospital Southampton, Clatterbridge Cancer Centre & Arrowe Park Hospital, Newcastle Freeman Hospital, King’s Lynn (Cambridge), Norfolk & Norwich (Cambridge), Sunderland Royal Hospital, Frimley Park Hospital, Royal Devon and Exeter Hospital, Wrexham Park Hospital, West Middlesex University Hospital, Royal United Hospital Bath, Betsi Calderwar Health Board, Lister Hospital, Hampshire (Basingstoke) Hospitals, University Hospital Coventry, Worcestershire Royal Hospital.
Trial Sponsor: Imperial College London
Trial Funder: Wellcome Trust
ClinicalTrials.gov Identifier: NCT03763253