TROG 18.01 phase III randomised clinical trial of the Novel Integration of New prostate radiation schedules with adJuvant Androgen deprivation: NINJA study protocol

Jarad Martin; Paul Keall; Shankar Siva; Peter Greer; David Christie; Kevin Moore; Jason Dowling; David Pryor; Peter Chong; Nicholas McLeod; Avi Raman; James Lynam; Joanne Smart; Christopher Oldmeadow; Colin I Tang; Declan G Murphy; Jeremy Millar; Keen Hun Tai; Lois Holloway; Penny Reeves; Amy Hayden; Tee Lim; Tanya Holt; Mark Sidhom

doi:10.1136/bmjopen-2019-030731

TROG 18.01 phase III randomised clinical trial of the Novel Integration of New prostate radiation schedules with adJuvant Androgen deprivation: NINJA study protocol

BMJ Open. 2019 Aug 20;9(8):e030731. doi: 10.1136/bmjopen-2019-030731.

Authors

Jarad Martin^{1

2}, Paul Keall³, Shankar Siva⁴, Peter Greer^{5

6}, David Christie⁷, Kevin Moore⁸, Jason Dowling⁹, David Pryor¹⁰, Peter Chong¹¹, Nicholas McLeod¹¹, Avi Raman¹¹, James Lynam², Joanne Smart⁵, Christopher Oldmeadow¹², Colin I Tang¹³, Declan G Murphy¹⁴, Jeremy Millar¹⁵, Keen Hun Tai⁴, Lois Holloway¹⁶, Penny Reeves^{2

17}, Amy Hayden¹⁸, Tee Lim¹⁹, Tanya Holt²⁰, Mark Sidhom¹⁶

Affiliations

¹ Department of Radiation Oncology, Calvary Mater Newcastle, Newcastle, New South Wales, Australia jarad.martin@calvarymater.org.au.
² School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia.
³ Radiation Physics Laboratory, University of Sydney, Sydney, New South Wales, Australia.
⁴ Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.
⁵ Department of Radiation Oncology, Calvary Mater Newcastle, Newcastle, New South Wales, Australia.
⁶ School of Mathematical and Physical Sciences, University of Newcastle, Callaghan, New South Wales, Australia.
⁷ Genesis Care, Southport, Queensland, Australia.
⁸ Department of Medical Physics, University of California San Diego, La Jolla, California, USA.
⁹ The Australian e-Health Research Centre, CSIRO, Canberra, Australian Capital Territory, Australia.
¹⁰ Department of Radiation Oncology, Princess Alexandra Hospital Health Service District, Woolloongabba, Queensland, Australia.
¹¹ Department of Urology, John Hunter Hospital, New Lambton Heights, New South Wales, Australia.
¹² Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
¹³ Department of Radiation Oncology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
¹⁴ Urological Service Team, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
¹⁵ Department of Radiation Oncology, Alfred Health, Melbourne, Victoria, Australia.
¹⁶ Department of Radiation Oncology, Liverpool Hospital, Liverpool, New South Wales, Australia.
¹⁷ Department of Health Research Economics, University of Newcastle Hunter Medical Research Institute, New Lambton, New South Wales, Australia.
¹⁸ Department of Radiation Oncology, Westmead Hospital, Westmead, New South Wales, Australia.
¹⁹ Genesis Care, Perth, Western Australia, Australia.
²⁰ Radiation Oncology Princess Alexandra Raymond Terrace, Brisbane, Queensland, Australia.

Abstract

Introduction: Stereotactic body radiotherapy (SBRT) is a non-invasive alternative to surgery for the treatment of non-metastatic prostate cancer (PC). The objectives of the Novel Integration of New prostate radiation schedules with adJuvant Androgen deprivation (NINJA) clinical trial are to compare two emerging SBRT regimens for efficacy with technical substudies focussing on MRI only planning and the use of knowledge-based planning (KBP) to assess radiotherapy plan quality.

Methods and analysis: Eligible patients must have biopsy-proven unfavourable intermediate or favourable high-risk PC, have an Eastern Collaborative Oncology Group (ECOG) performance status 0-1 and provide written informed consent. All patients will receive 6 months in total of androgen deprivation therapy. Patients will be randomised to one of two SBRT regimens. The first will be 40 Gy in five fractions given on alternating days (SBRT monotherapy). The second will be 20 Gy in two fractions given 1 week apart followed 2 weeks later by 36 Gy in 12 fractions given five times per week (virtual high-dose rate boost (HDRB)). The primary efficacy outcome will be biochemical clinical control at 5 years. Secondary endpoints for the initial portion of NINJA look at the transition of centres towards MRI only planning and the impact of KBP on real-time (RT) plan assessment. The first 150 men will demonstrate accrual feasibility as well as addressing the KBP and MRI planning aims, prior to proceeding with total accrual to 472 patients as a phase III randomised controlled trial.

Ethics and dissemination: NINJA is a multicentre cooperative clinical trial comparing two SBRT regimens for men with PC. It builds on promising results from several single-armed studies, and explores radiation dose escalation in the Virtual HDRB arm. The initial component includes novel technical elements, and will form an important platform set for a definitive phase III study.

Trial registration number: ANZCTN 12615000223538.

Keywords: computer-assisted radiotherapy planning; image-guided radiotherapy; intensity modulated radiotherapy; prostatic neoplasms; radiotherapy; radiotherapy dose hypofractionation; stereotactic body radiotherapy.

Publication types

Clinical Trial Protocol
Research Support, Non-U.S. Gov't

MeSH terms

Androgen Antagonists / therapeutic use*
Chemotherapy, Adjuvant / standards*
Clinical Trials, Phase III as Topic
Combined Modality Therapy
Humans
Male
Neoplasm Staging
Prostatic Neoplasms / therapy*
Radiosurgery / standards*

Substances

Androgen Antagonists

Associated data

ANZCTR/ANZCTN12615000223538