Additional Treatments to the Local tumour for metastatic prostate cancer-Assessment of Novel Treatment Algorithms (IP2-ATLANTA): protocol for a multicentre, phase II randomised controlled trial

Introduction Survival in men diagnosed with de novo synchronous metastatic prostate cancer has increased following the use of upfront systemic treatment, using chemotherapy and other novel androgen receptor targeted agents, in addition to standard androgen deprivation therapy (ADT). Local cytoreduct...

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Main Authors: Francesca Fiorentino, Iqbal Shergill, John McGrath, Manal Kumar, Martin John Connor, Taimur Tariq Shah, Katarzyna Smigielska, Emily Day, Johanna Sukumar, Naveed Sarwar, Michael Gonzalez, Alison Falconer, Natalia Klimowska-Nassar, Martin Evans, Olivia Frances Naismith, Kamalram Thippu Jayaprakash, Derek Price, Shiva Gayadeen, Dolan Basak, Gail Horan, Denise Sheehan, Azman Ibrahim, Cathryn Brock, Rachel A. Pearson, Nicola Anyamene, Catherine Heath, Bhavan Rai, Giles Hellawell, Stuart McCracken, Bijan Khoubehi, Stephen Mangar, Vincent Khoo, Tim Dudderidge, John Nicholas Staffurth, Mathias Winkler, Hashim Uddin Ahmed
Format: Article
Language:English
Published: BMJ Publishing Group 2021-02-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/11/2/e042953.full
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author Francesca Fiorentino
Iqbal Shergill
John McGrath
Manal Kumar
Martin John Connor
Taimur Tariq Shah
Katarzyna Smigielska
Emily Day
Johanna Sukumar
Naveed Sarwar
Michael Gonzalez
Alison Falconer
Natalia Klimowska-Nassar
Martin Evans
Olivia Frances Naismith
Kamalram Thippu Jayaprakash
Derek Price
Shiva Gayadeen
Dolan Basak
Gail Horan
Denise Sheehan
Azman Ibrahim
Cathryn Brock
Rachel A. Pearson
Nicola Anyamene
Catherine Heath
Bhavan Rai
Giles Hellawell
Stuart McCracken
Bijan Khoubehi
Stephen Mangar
Vincent Khoo
Tim Dudderidge
John Nicholas Staffurth
Mathias Winkler
Hashim Uddin Ahmed
author_facet Francesca Fiorentino
Iqbal Shergill
John McGrath
Manal Kumar
Martin John Connor
Taimur Tariq Shah
Katarzyna Smigielska
Emily Day
Johanna Sukumar
Naveed Sarwar
Michael Gonzalez
Alison Falconer
Natalia Klimowska-Nassar
Martin Evans
Olivia Frances Naismith
Kamalram Thippu Jayaprakash
Derek Price
Shiva Gayadeen
Dolan Basak
Gail Horan
Denise Sheehan
Azman Ibrahim
Cathryn Brock
Rachel A. Pearson
Nicola Anyamene
Catherine Heath
Bhavan Rai
Giles Hellawell
Stuart McCracken
Bijan Khoubehi
Stephen Mangar
Vincent Khoo
Tim Dudderidge
John Nicholas Staffurth
Mathias Winkler
Hashim Uddin Ahmed
author_sort Francesca Fiorentino
collection DOAJ
description Introduction Survival in men diagnosed with de novo synchronous metastatic prostate cancer has increased following the use of upfront systemic treatment, using chemotherapy and other novel androgen receptor targeted agents, in addition to standard androgen deprivation therapy (ADT). Local cytoreductive and metastasis-directed interventions are hypothesised to confer additional survival benefit. In this setting, IP2-ATLANTA will explore progression-free survival (PFS) outcomes with the addition of sequential multimodal local and metastasis-directed treatments compared with standard care alone.Methods A phase II, prospective, multicentre, three-arm randomised controlled trial incorporating an embedded feasibility pilot. All men with new histologically diagnosed, hormone-sensitive, metastatic prostate cancer, within 4 months of commencing ADT and of performance status 0 to 2 are eligible. Patients will be randomised to Control (standard of care (SOC)) OR Intervention 1 (minimally invasive ablative therapy to prostate±pelvic lymph node dissection (PLND)) OR Intervention 2 (cytoreductive radical prostatectomy±PLND OR prostate radiotherapy±pelvic lymph node radiotherapy (PLNRT)). Metastatic burden will be prespecified using the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED) definition. Men with low burden disease in intervention arms are eligible for metastasis-directed therapy, in the form of stereotactic ablative body radiotherapy (SABR) or surgery. Standard systemic therapy will be administered in all arms with ADT±upfront systemic chemotherapy or androgen receptor agents. Patients will be followed-up for a minimum of 2 years. Primary outcome: PFS. Secondary outcomes include predictive factors for PFS and overall survival; urinary, sexual and rectal side effects. Embedded feasibility sample size is 80, with 918 patients required in the main phase II component. Study recruitment commenced in April 2019, with planned follow-up completed by April 2024.Ethics and dissemination Approved by the Health Research Authority (HRA) Research Ethics Committee Wales-5 (19/WA0005). Study results will be submitted for publication in peer-reviewed journals.Trial registration number NCT03763253; ISCRTN58401737
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spelling doaj-art-5990ac2cc8ae4ff48516b35753c3f0482024-11-17T08:05:09ZengBMJ Publishing GroupBMJ Open2044-60552021-02-0111210.1136/bmjopen-2020-042953Additional Treatments to the Local tumour for metastatic prostate cancer-Assessment of Novel Treatment Algorithms (IP2-ATLANTA): protocol for a multicentre, phase II randomised controlled trialFrancesca Fiorentino0Iqbal Shergill1John McGrath2Manal Kumar3Martin John Connor4Taimur Tariq Shah5Katarzyna Smigielska6Emily Day7Johanna Sukumar8Naveed Sarwar9Michael Gonzalez10Alison Falconer11Natalia Klimowska-Nassar12Martin Evans13Olivia Frances Naismith14Kamalram Thippu Jayaprakash15Derek Price16Shiva Gayadeen17Dolan Basak18Gail Horan19Denise Sheehan20Azman Ibrahim21Cathryn Brock22Rachel A. Pearson23Nicola Anyamene24Catherine Heath25Bhavan Rai26Giles Hellawell27Stuart McCracken28Bijan Khoubehi29Stephen Mangar30Vincent Khoo31Tim Dudderidge32John Nicholas Staffurth33Mathias Winkler34Hashim Uddin Ahmed35Department of Surgery and Cancer, Imperial College London, London, UKDepartment of Urology, Wrexham Maelor Hospital, Wrexham, UK2 Social & Scientific Systems, a DLH Holding Company, Durham, North Carolina, USADepartment of Urology, Arrowe Park Hospital, Wirral University Teaching Hospital NHS Foundation Trust, Wirral, UKImperial Prostate, Division of Surgery, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UKImperial Prostate, Division of Surgery, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UKImperial Prostate, Division of Surgery, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UKImperial College Clinical Trials Unit, Imperial College London, London, UKImperial College Clinical Trials Unit, Imperial College London, London, UKDepartment of Oncology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UKDepartment of Oncology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UKDepartment of Oncology, Imperial College Healthcare NHS Trust, London, UKImperial Prostate, Divison of Surgery, Department of Surgery and Cancer, Imperial College London, London, UKImperial Prostate, Division of Surgery, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UKRadiotherapy Trials Quality Assurance (RTTQA), Royal Marsden NHS Foundation Trust, London, UKDepartment of Oncology, Addenbrookes Hospital, Cambridge, Cambridgeshire, UKDepartment of Surgery and Cancer, Imperial College London, London, UKDepartment of Oncology, Imperial College Healthcare NHS Trust, London, UKDepartment of Oncology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UKDepartment of Oncology, Addenbrooke’s Hospital, Cambridge, UKDepartment of Oncology, Royal Devon and Exeter NHS Foundation Trust, Exeter, Devon, UKDepartment of Clinical Oncology, Clatterbridge Cancer Centre NHS Foundation Trust, Bebington, Wirral, UKDepartment of Oncology, Chelsea and Westminster Hospital NHS Foundation Trust, London, UKDepartment of Oncology, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UKDepartment of Oncology, London North West University Healthcare NHS Trust, Harrow, London, UKDepartment of Radiotherapy, University Hospital Southampton NHS Foundation Trust, Southampton, UKDepartment of Urology, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UKDepartment of Urology, Northwick Park Hospital, London North West University Healthcare NHS Trust, Harrow, London, UKDepartment of Urology, Sunderland Royal Hospital, Sunderland, UKDepartment of Urology, Chelsea and Westminster Hospital NHS Foundation Trust, London, UKDepartment of Oncology, Imperial College Healthcare NHS Trust, London, UKDepartment of Oncology, Royal Marsden NHS Foundation Trust, London, UKDepartment of Urology, University Hospital Southampton NHS Foundation Trust, Southampton, UKDivision of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UKImperial Prostate, Divison of Surgery, Department of Surgery and Cancer, Imperial College London, London, UKImperial Prostate, Divison of Surgery, Department of Surgery and Cancer, Imperial College London, London, UKIntroduction Survival in men diagnosed with de novo synchronous metastatic prostate cancer has increased following the use of upfront systemic treatment, using chemotherapy and other novel androgen receptor targeted agents, in addition to standard androgen deprivation therapy (ADT). Local cytoreductive and metastasis-directed interventions are hypothesised to confer additional survival benefit. In this setting, IP2-ATLANTA will explore progression-free survival (PFS) outcomes with the addition of sequential multimodal local and metastasis-directed treatments compared with standard care alone.Methods A phase II, prospective, multicentre, three-arm randomised controlled trial incorporating an embedded feasibility pilot. All men with new histologically diagnosed, hormone-sensitive, metastatic prostate cancer, within 4 months of commencing ADT and of performance status 0 to 2 are eligible. Patients will be randomised to Control (standard of care (SOC)) OR Intervention 1 (minimally invasive ablative therapy to prostate±pelvic lymph node dissection (PLND)) OR Intervention 2 (cytoreductive radical prostatectomy±PLND OR prostate radiotherapy±pelvic lymph node radiotherapy (PLNRT)). Metastatic burden will be prespecified using the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED) definition. Men with low burden disease in intervention arms are eligible for metastasis-directed therapy, in the form of stereotactic ablative body radiotherapy (SABR) or surgery. Standard systemic therapy will be administered in all arms with ADT±upfront systemic chemotherapy or androgen receptor agents. Patients will be followed-up for a minimum of 2 years. Primary outcome: PFS. Secondary outcomes include predictive factors for PFS and overall survival; urinary, sexual and rectal side effects. Embedded feasibility sample size is 80, with 918 patients required in the main phase II component. Study recruitment commenced in April 2019, with planned follow-up completed by April 2024.Ethics and dissemination Approved by the Health Research Authority (HRA) Research Ethics Committee Wales-5 (19/WA0005). Study results will be submitted for publication in peer-reviewed journals.Trial registration number NCT03763253; ISCRTN58401737https://bmjopen.bmj.com/content/11/2/e042953.full
spellingShingle Francesca Fiorentino
Iqbal Shergill
John McGrath
Manal Kumar
Martin John Connor
Taimur Tariq Shah
Katarzyna Smigielska
Emily Day
Johanna Sukumar
Naveed Sarwar
Michael Gonzalez
Alison Falconer
Natalia Klimowska-Nassar
Martin Evans
Olivia Frances Naismith
Kamalram Thippu Jayaprakash
Derek Price
Shiva Gayadeen
Dolan Basak
Gail Horan
Denise Sheehan
Azman Ibrahim
Cathryn Brock
Rachel A. Pearson
Nicola Anyamene
Catherine Heath
Bhavan Rai
Giles Hellawell
Stuart McCracken
Bijan Khoubehi
Stephen Mangar
Vincent Khoo
Tim Dudderidge
John Nicholas Staffurth
Mathias Winkler
Hashim Uddin Ahmed
Additional Treatments to the Local tumour for metastatic prostate cancer-Assessment of Novel Treatment Algorithms (IP2-ATLANTA): protocol for a multicentre, phase II randomised controlled trial
BMJ Open
title Additional Treatments to the Local tumour for metastatic prostate cancer-Assessment of Novel Treatment Algorithms (IP2-ATLANTA): protocol for a multicentre, phase II randomised controlled trial
title_full Additional Treatments to the Local tumour for metastatic prostate cancer-Assessment of Novel Treatment Algorithms (IP2-ATLANTA): protocol for a multicentre, phase II randomised controlled trial
title_fullStr Additional Treatments to the Local tumour for metastatic prostate cancer-Assessment of Novel Treatment Algorithms (IP2-ATLANTA): protocol for a multicentre, phase II randomised controlled trial
title_full_unstemmed Additional Treatments to the Local tumour for metastatic prostate cancer-Assessment of Novel Treatment Algorithms (IP2-ATLANTA): protocol for a multicentre, phase II randomised controlled trial
title_short Additional Treatments to the Local tumour for metastatic prostate cancer-Assessment of Novel Treatment Algorithms (IP2-ATLANTA): protocol for a multicentre, phase II randomised controlled trial
title_sort additional treatments to the local tumour for metastatic prostate cancer assessment of novel treatment algorithms ip2 atlanta protocol for a multicentre phase ii randomised controlled trial
url https://bmjopen.bmj.com/content/11/2/e042953.full
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