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

Martin John Connor, Taimur Tariq Shah, Katarzyna Smigielska, Emily Day, Johanna Sukumar, Francesca Fiorentino, 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, John McGrath, Denise Sheehan, Manal Kumar, Azman Ibrahim, Cathryn Brock, Rachel A Pearson, Nicola Anyamene, Catherine Heath, Iqbal Shergill, Bhavan Rai, Giles Hellawell, Stuart McCracken, Bijan Khoubehi, Stephen Mangar, Vincent Khoo, Tim Dudderidge, John Nicholas Staffurth, Mathias Winkler, Hashim Uddin Ahmed, Martin John Connor, Taimur Tariq Shah, Katarzyna Smigielska, Emily Day, Johanna Sukumar, Francesca Fiorentino, 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, John McGrath, Denise Sheehan, Manal Kumar, Azman Ibrahim, Cathryn Brock, Rachel A Pearson, Nicola Anyamene, Catherine Heath, Iqbal Shergill, Bhavan Rai, Giles Hellawell, Stuart McCracken, Bijan Khoubehi, Stephen Mangar, Vincent Khoo, Tim Dudderidge, John Nicholas Staffurth, Mathias Winkler, Hashim Uddin Ahmed

Abstract

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.

Keywords: genitourinary imaging; prostate disease; radiation oncology; radiotherapy; urological tumours; urology.

Conflict of interest statement

Competing interests: MJC’s research is support by University College London Hospitals (UCLH) Charity and the Wellcome Trust.KTJ is currently supported by a research grant from the UK National Institute of Health Research (NIHR) Clinical Research Network Eastern. He has received educational and travel grants from Bayer UK, Janssen Oncology, Pfizer; Roche, Takeda.HUA’s research is supported by core funding from the United Kingdom’s National Institute of Health Research (NIHR) Imperial Biomedical Research Centre. HUA currently receives funding from the Wellcome Trust, Prostate Cancer UK, MRC (UK), Cancer Research UK, Sonacare Inc., Trod Medical and Sophiris Biocorp for trials in prostate cancer. HUA was a paid medical consultant for Sophiris Biocorp, Sonacare Inc. and BTG in the past 3 years.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1
Figure 1
Study flowchart. CRP, cytoreductive radical prostatectomy; EBRT, external beam radiotherapy; MIAT, minimally invasive ablative therapy; PLND, pelvic lymph node dissection; PLNRT, pelvic lymph node radiotherapy; RCT, randomised controlled trial; SOC, standard of care. *Systemic therapy is not limited to listed agents. *Prostate only EBRT may be performed in selected men with low-burden disease, if declared prior to randomisation and local SOC.

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