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Trial registered on ANZCTR


Registration number
ACTRN12618001806257
Ethics application status
Approved
Date submitted
2/11/2018
Date registered
6/11/2018
Date last updated
1/04/2019
Date data sharing statement initially provided
6/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The NINJA Clinical Trial: Novel Integration of New prostate radiation schedules with adJuvant Androgen deprivation for patients with intermediate or low-high risk prostate cancer.
Scientific title
The NINJA Clinical Trial: Novel Integration of New prostate radiation schedules with adJuvant Androgen deprivation
Secondary ID [1] 295490 0
TROG 18.01
Universal Trial Number (UTN)
U111-1217-1305
Trial acronym
NINJA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 308759 0
Condition category
Condition code
Cancer 307690 307690 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
ARM 1: Stereotactic Body Radiotherapy (SBRT) Monotherapy: 40Gy in 5 fractions delivered 1-3x/week (typically 5 treatments given over 2 weeks)
ARM2: Virtual High Dose Rate Brachytherapy (HDRB) Boost: 20gy in 2 fractions delivered once a week followed by a 2 week break and then 36Gy in 12 fractions delivered 4-5x/week. (2 treatments given 1 week apart, combined with a shorter version of conventional external beam radiotherapy)
All participants irrespective of the radiotherapy treatment arm they are allocated will commence 6 months of androgen deprivation therapy (ADT) prior to receiving radiotherapy (approximately 3 to 4 months prior). ADT is given via injection and is considered part of the standard of care for participants eligible for this study. The dose, frequency and administration is dependent on that prescribed by the clinician.
This study will also look at better ways in which we can plan radiotherapy treatment for men with prostate cancer using Magnetic Resonance Imaging (MRI scans) for radiotherapy planning.
Intervention code [1] 301811 0
Treatment: Other
Comparator / control treatment
The comparator/control treatment for this study is the SBRT monotherapy (Arm 1). The aim is to demonstrate that virtual HDRB boost is superior to SBRT monotherapy.
Control group
Active

Outcomes
Primary outcome [1] 307976 0
Rate of Biochemical Clinical Control (BCC). Prostate cancer biochemical control measured by Phoenix definition of nadir + 2ng/mL (blood PSA measurement) and/or detection of metastases (imaging or other) or initiation of salvage intervention (further treatment) by the 5 year time point
Timepoint [1] 307976 0
Assessed 6 wks post SBRT and then 6 monthly up to 5 years
Secondary outcome [1] 353549 0
Rate of replanning following Knowledge Based Planning (KBP) feedback to trial centres. Rate of replanning prior to radiotherapy treatment performed by trial centres following KBP comparison against initial plan. In KBP, a model is developed using a range of patient anatomies and target volumes. This can then be rapidly applied to a new case to either generate a plan de novo, or compare with a conventional plan.
Timepoint [1] 353549 0
Within 12 months after first 150 participants accrued.
Secondary outcome [2] 353550 0
Rate of trial centre conversion to prostate Magnetic Resonance Imaging (MRI) only planning. The rate of full conversion to MRI based prostate radiotherapy planning (i.e. CT scan no longer required to complete radiotherapy planning). Modern RT planning uses electron density from a CT dataset to calculate dose. Many centres now acquire both a CT and a MRI.
Timepoint [2] 353550 0
Within 12 months after first 150 participants accrued

Eligibility
Key inclusion criteria
Unfavourable intermediate or low-high risk prostate cancer
- ISUP 2 AND EITHER PSA 10-20, OR T2b/c AND greater than or equal to 50% Biopsy Cores Positive
- ISUP 3 AND PSA less than or equal to 20 OR
- ISUP 4-5 (NOT predominant pattern 5 disease) OR T3a AND PSA less than and equal to 20
Staging investigations showing N0M0 disease performed within 60 days prior to commencing ADT or antiandrogen:
- For high risk patients, PSMA PET staging within 60 days prior to study entry showing N0M0 disease.
- For unfavourable intermediate risk patients, either PSMA PET alone OR whole body bone scan AND EITHER CT abdomen/pelvis OR MRI prostate/pelvis.
Histologically confirmed prostate cancer
ECOG performance status of 0-1.
Life expectancy greater than 5 years.
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Higher risk prostate cancer:
- T3b or T4 based on all clinical information available including examination and investigations
- PSA greater than 20
- Dominant pattern 5 histology (ie Gleason score 5+4 or 5+5)
Previous pelvic radiotherapy
Prior diagnosis of cancer that was:
- more than 5 years prior to current diagnosis with subsequent evidence of disease recurrence or clinical expectation of recurrence is greater than 10%
- within 5 years of current diagnosis with the exception of successfully treated basal cell or squamous cell skin carcinoma or carcinoma in situ of the cervix
Patients with clinical evidence of metastatic disease.
Presence of total hip joint replacement
Clinical Target volume greater than 100cc
Severe obstructive lower urinary tract symptoms (IPSS greater than an equal to 20)
Any contraindications to performance of a planning MRI

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer. The Trial Coordinating Centre is responsible for randomising the participant through the randomisation program, and informing the site of the randomisation number and the treatment allocation for the participant randomised in real time. The Trial Coordinator at the participating centre then gives the information about treatment allocation to the trial participant, and treating clinical team. The assignment schedule is unpredictable and those enrolling and assigning participants will not obtain access to the randomisation method. Once a patient is registered on the trial, registration will not be cancelled. The randomization sequence will be hidden in a password protected manner from the staff involved in the trial enrolment process.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be on a 1:1 ratio between the two arms of SBRT Monotherapy (initially experimental arm one, aiming to transition to the standard arm assuming non-inferiority of this approach demonstrated compared with more conventional regimens in randomized control trials) and ‘Virtual HDR Boost’ radiotherapy (initially experimental arm two, transitioning to the sole experimental arm). This is an unblinded study.
Randomisation is via a computer generated sequence, with stratification by risk category (unfavourable intermediate and high) and centre. A validated randomization method will be used via https://www.sealedenvelope.com/.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The statistical justification required to achieve the primary efficacy endpoint follows. Using a similar endpoint as well as a short course of ADT, the CHHiP study 60 Gy arm had 90.2% and 84.2% BCC for intermediate and high risk patients respectively at the 5 year time point. The ASCENDE-RT study also included intermediate and high risk men, managed with 12 months of ADT, and the experimental arm delivered 46 Gy in 23 fractions of EBRT alongside a Brachytherapy boost, a regimen attempting to be emulated in the current study. At 5 years, the BCC was 89%, although with a higher risk patient mix than we are going to accrue on this protocol. Allowing for differences in inter-trial comparisons, it would appear reasonable to expect BCC 86% in the standard SBRT arm. Similar data has been reported for single arm SBRT monotherapy series. For a superiority RCT design, we will aim for a hazard ratio of 0.5 in 5-yr BCC for the virtual HDR arm ie 93%. An HR of 0.5 is chosen because this translates to an absolute improvement of 7%, and any improvements less than this are unlikely to be clinically significant for this particular surrogate endpoint. With alpha 0.05, power of 80%, and drop out of 2% the required phase 3 sample size is 472 men.
For KBP, we hypothesize that a replanning rate of greater than 15% would be clinically significant. Assuming an error rate of plus or minus 6%, at an alpha of 5% with power of 80%, 136 participants are required. Allow 10% drop-out due to technical issues with a new planning paradigm: total of 150 cases.
For MRI planning, having greater than an equal to 50% of centres involved in this aspect of NINJA completely transition to MRI only planning will be deemed a success.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 12348 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 12349 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [3] 12350 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [4] 12351 0
Blacktown Hospital - Blacktown
Recruitment hospital [5] 12352 0
Westmead Hospital - Westmead
Recruitment hospital [6] 12353 0
Campbelltown Hospital - Campbelltown
Recruitment postcode(s) [1] 24589 0
2170 - Liverpool
Recruitment postcode(s) [2] 24590 0
2298 - Waratah
Recruitment postcode(s) [3] 24591 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 24592 0
2148 - Blacktown
Recruitment postcode(s) [5] 24593 0
2145 - Westmead
Recruitment postcode(s) [6] 24594 0
2560 - Campbelltown

Funding & Sponsors
Funding source category [1] 300077 0
Commercial sector/Industry
Name [1] 300077 0
Mundipharma Pty Limited
Address [1] 300077 0
Level 24, 88 Phillip Street, Sydney NSW 2000
Country [1] 300077 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Trans Tasman Radiation Oncology Group (TROG)
Address
Edith Street Waratah NSW 2289
Country
Australia
Secondary sponsor category [1] 299475 0
Other Collaborative groups
Name [1] 299475 0
Australian and New Zealand Urogenital and Prostate cancer trials group (ANZUP)
Address [1] 299475 0
Life House L6 119-143 Missenden Road Camperdown NSW 2050
Country [1] 299475 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300924 0
South Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 300924 0
Locked Bag 7103, Liverpool BC, NSW 1871
Ethics committee country [1] 300924 0
Australia
Date submitted for ethics approval [1] 300924 0
28/09/2018
Approval date [1] 300924 0
15/10/2018
Ethics approval number [1] 300924 0
HREC/18/LPOOL/420

Summary
Brief summary
The NINJA clinical trial aims to compare two emerging schedules of radiotherapy in the treatment of prostate cancer.

Who is it for?
You may be eligible for this study if you are an adult male over the age of 18 who has been diagnosed with intermediate or high risk prostate cancer .

Study details
Participants will be randomly assigned to one of two radiotherapy schedules as part of this study. In schedule 1 (called Sterotactic Body Radiotherapy) participants will receive 5 radiotherapy treatments over 2 weeks and in schedule 2 (called Virtual High Dose Rate Boost) participants will receive Sterotactic Body Radiotherapy delivered in 2 treatments over 1 week followed by 12 treatments of conventional external beam radiotherapy over 2 and a half weeks.
A blood test will be collected at the initial assessment, 6 weeks after radiotherapy and 6 monthly for a period of 5 years. Questionnaires will completed at the initial assessment, 6 weeks after radiotherapy and at 2 and 5 years.

It is hoped that this research will potentially improve the accuracy and quality of radiotherapy treatment in prostate cancer.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 85298 0
A/Prof Jarad Martin
Address 85298 0
Radiation Oncology
Calvary Mater Newcastle
Corner Edith and Platt Streets
Waratah NSW 2298
Country 85298 0
Australia
Phone 85298 0
+61 2 4014 3631
Fax 85298 0
+61 2 4014 3169
Email 85298 0
Jarad.Martin@calvarymater.org.au
Contact person for public queries
Name 85299 0
Mrs Jo Smart
Address 85299 0
Radiation Oncology
Calvary Mater Newcastle
Corner Edith and Platt Streets
Waratah NSW 2298
Country 85299 0
Australia
Phone 85299 0
+61 2 4014 3947
Fax 85299 0
+61 2 4014 3945
Email 85299 0
Joanne.Smart@calvarymater.org.au
Contact person for scientific queries
Name 85300 0
A/Prof Jarad Martin
Address 85300 0
Radiation Oncology
Calvary Mater Newcastle
Corner Edith and Platt Streets
Waratah NSW 2298
Country 85300 0
Australia
Phone 85300 0
+61 2 4014 3631
Fax 85300 0
+61 2 4014 3169
Email 85300 0
Jarad.Martin@calvarymater.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Unknown at this stage
What supporting documents are/will be available?
No other documents available
Summary results
No Results