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Trial registered on ANZCTR


Registration number
ACTRN12615000223538
Ethics application status
Approved
Date submitted
18/02/2015
Date registered
9/03/2015
Date last updated
16/09/2019
Date data sharing statement initially provided
16/09/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Multicentre External Beam Radiotherapy Study Using Stereotactic Boost for Prostate Cancer Patients
Scientific title
A Phase 2 Multicentre Clinical Trial Exploring the Safety and Feasibility of a Stereotactic Radiotherapy Boost to the Prostate with Fractionated External Beam Radiotherapy in Men with Prostate Cancer
Secondary ID [1] 286187 0
Nil known
Universal Trial Number (UTN)
U1111-1167-2997
Trial acronym
Prometheus
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 294216 0
Condition category
Condition code
Cancer 294534 294534 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Stereotactic body radiotherapy (SBRT) allows high doses of radiotherapy to be delivered using external beam radiotherapy to a similar dose that is achieved using brachytherapy. The study investigates if stereotactic radiotherapy can be as safe and as effective as brachytherapy without the need for an invasive surgical procedure involved with delivering brachytherapy. The main reason for this study is to try to replicate this technique in Australia using equipment available in all radiotherapy departments.
This study also includes a mechanism for SBRT dose escalation. A minimum of 20 men are to complete treatment without >15% suffering a grade 3 acute toxicity or any episodes of grade 4 acute toxicity at a particular dose level. The individual centre must also accrue >5 patients at the previous dose level prior to exploring dose escalation. Once this is satisfied the SBRT dose is to increase by 1Gy. The initial dose will be 19Gy, therefore the first dose escalation will be to 20Gy. This process can be followed a maximum of three times, to a maximum SBRT dose of 22Gy.
Radiotherapy can cause damage to the lower part of the bowel, known as the rectum, which is right next to the prostate. Two methods are available to try to reduce the risk of any damage to the rectum by moving the rectum a little further away from the prostate. Firstly, a device called Rectafix could be used in this study to do this. It involves inserting a probe the same size as a finger into the back passage and using it to angle the rectum away from the prostate inserted only for the duration of the radiotherapy planning, and only for the duration of the two stereotactic radiotherapy treatments. Secondly, a water based gel called SpaceOAR could also be used in this study to do this. It involves inserting this gel in the space between the prostate and rectum 1-2 weeks before radiotherapy planning. Either of these rectal displacement techniques (Rectafix or SpaceOAR) will be utilised at the doctor's discretion in consultation with the participating patients. The stereotactic radiotherapy dose (given over two treatments one week apart) and the external beam dose (46Gy in 23 fractions or 36Gy in 12 fractions depending on the centre) is the same irrespective of the rectal separation technique employed.
Intervention code [1] 291201 0
Treatment: Devices
Intervention code [2] 291319 0
Treatment: Other
Comparator / control treatment
Not applicable
Control group
Uncontrolled

Outcomes
Primary outcome [1] 294314 0
Feasibility of administering radiotherapy dose escalation to the prostate via a Stereotactic Body Radiation Therapy (SBRT) boost using a linear accelerator in the multicenter setting. Feasibility is defined as three or more centres treating five or more patients, and at least two centres achieving further dose escalation
Timepoint [1] 294314 0
End of study
Primary outcome [2] 294315 0
Safety of radiotherapy dose escalation to the prostate via a Stereotactic Body Radiation Therapy (SBRT) boost using a linear accelerator in the multicenter setting assessed by comparing measured side effects with that expected from standard dose escalated external beam radiotherapy.
Timepoint [2] 294315 0
Side effects are assessed at six weeks after radiotherapy, and then at six monthly intervals for three years then annually for another two years.
Secondary outcome [1] 313018 0
Patient tolerance assessed by quality of life questionnaires (Expanded Prostate Cancer Index Composite (EPIC) and tolerability of Rectafix and SpaceOAR questionnaires that have been designed specifically for the use in this study).
Timepoint [1] 313018 0
The EPIC is assessed at baseline, at the end of radiotherapy and then at 12 months, 36 months and 60 months after radiotherapy, The tolerability of Rectafix and SpaceOAR questionnaires are assessed at 6 weeks after radiotherapy.
Secondary outcome [2] 313336 0
Cancer control assessed by biochemical response and freedom from clinical signs of tumour recurrence.
Timepoint [2] 313336 0
Assessed at six weeks after radiotherapy, and then at six monthly intervals for three years then annually for another two years.
Secondary outcome [3] 313337 0
Prostate motion assessed by MRI scans, and real time imaging during radiotherapy of prostate position.
Timepoint [3] 313337 0
At planning and during treatment.

Eligibility
Key inclusion criteria
1. Patient capable of giving informed consent
2. Histological diagnosis of prostate cancer (PC)
3. Intermediate or High risk disease respectively defined by any one of:
a.Baseline PSA 10-20, Gleason grade 7 disease, Clinical stage T2b-c OR
b.Baseline PSA greater than or equal to 20, Gleason grade 8-10 disease, Clinical stage T3
4. For high risk patients, negative conventional staging in the form of a:
a. PSMA PET scan OR
b. T99m whole body bone scan AND
b. Either CT of the abdomen and pelvis or MRI pelvis
5. No previous pelvic radiotherapy
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. ECOG performance status >1
2. Hip prosthesis
3. Inability to have intraprostatic fiducials inserted.
4. Inability to have a MRI due to:
a. Implanted magnetic metal eg intraocular metal
b. Pacemaker / Implantable defibrillator
c. Extreme claustrophobia
5. Clinical stage T4 (tumour invasion into adjacent anatomical structures)
6. Inflammatory bowel disease
7. Severe obstructive urinary symptoms
8. Inability to meet planning objectives

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety
Statistical methods / analysis
This will fall into 5 general categories:
1. Feasibility: The protocol is deemed to be feasible if all of the following criteria are met:
- At least 3 different centres participate.
- Each centre accrues at least 5 patients.
- At least two centres attempt dose escalation.

2. Toxicity:
- Acute: The incidences of CTCAE acute grade 2 and 3 GI and GU toxicity will be reported separately (ie GI and GU) as a fraction of all patients treated. An incidence of >15% grade 3 GU or GI (excluding erectile dysfunction) toxicity attributable to radiotherapy at any individual dose level would require halting the protocol for further investigation of underlying causes. Similarly, any reports of grade 4 toxicity would require halting the protocol for further investigation of underlying causes.
- Late: The actuarial rates of CTCAE late grade 2-3 GI and GU toxicity will be calculated and reported at the 3 year mark. Studies using HDRB boost as well as IG-IMRT suggest rates of 5-15% are achievable. The study will be powered to recruit sufficient numbers to be confident that <15% of men will have either a grade 2-3 GI or grade 2-3 GU late GU event. The formula is:

n = (1.96/E)2 p(1-p)

where E is the margin of error. A conservative upper estimate of p here is 0.225 (the probability of an event). E might be 0.05 since that at worst gives a 95% CI as 0.15+/-0.05. With these figures n = 268.

3. Patient Tolerance: Summary figures will be produced from the questionnaire.

4. Cancer Control: Main endpoint is bNED calculated by the Phoenix definition of nadir+2. To be reported as survival curves both for the population overall at the 3 year mark, but also individually for intermediate and high risk patients.

5. Prostate motion: A software called SeedTracker is used to track prostate motion (only used if software is available at site). The incidence of couch shifts will be reported, as will the magnitude of all mismatches, and if imaging is performed during treatment, the magnitude and direction of intrafraction motion will be reported. If cine-MRI is performed, the movement in anterior-posterior and superior-inferior planes at the time of simulation can be compared with movements occurring during treatment.

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] 3455 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [2] 3456 0
Liverpool Hospital - Liverpool
Recruitment hospital [3] 3457 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [4] 3459 0
St George Hospital - Kogarah
Recruitment hospital [5] 3460 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [6] 11561 0
Mater Adult Hospital - South Brisbane
Recruitment postcode(s) [1] 9226 0
2298 - Waratah
Recruitment postcode(s) [2] 9227 0
2170 - Liverpool
Recruitment postcode(s) [3] 9228 0
2560 - Campbelltown
Recruitment postcode(s) [4] 9230 0
2217 - Kogarah
Recruitment postcode(s) [5] 9231 0
4102 - Woolloongabba
Recruitment postcode(s) [6] 23605 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 290759 0
Self funded/Unfunded
Name [1] 290759 0
Address [1] 290759 0
Country [1] 290759 0
Primary sponsor type
Individual
Name
Dr Mark Sidhom
Address
Liverpool Hospital
Corner of Elizabeth and Goulburn Sts
Liverpool
New South Wales 2170, Australia
Country
Australia
Secondary sponsor category [1] 289446 0
Individual
Name [1] 289446 0
A/Prof Jarad Martin
Address [1] 289446 0
Calvary Mater Hospital Newcastle
Edith St
Waratah, Newcastle
New South Wales 2298, Australia
Country [1] 289446 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292391 0
South Western Sydney Local Health District
Ethics committee address [1] 292391 0
Research and Ethics Office
Locked Bag 7103
Liverpool BC
NSW 2871
Ethics committee country [1] 292391 0
Australia
Date submitted for ethics approval [1] 292391 0
Approval date [1] 292391 0
02/12/2013
Ethics approval number [1] 292391 0
HREC/13/LPOOL/311

Summary
Brief summary
The aim of this study is to investigate the safety and feasibility of an advanced technique of external beam radiotherapy, termed stereotactic body radiotherapy (SBRT), in men with prostate cancer. Who is it for? You may be eligible to join this study if you are a male aged 18 years or above who has a confirmed diagnosis of intermediate or high risk prostate cancer. Study details Studies have shown that escalated doses of radiotherapy increase cure rates for prostate cancer. Higher doses are achievable with high dose rate (HDR) brachytherapy, and data suggests outcomes are superior. However, HDR brachytherapy is invasive, expensive and requires access to operating theatres and specialised equipment. In this study we aim to investigate whether an advanced technique of external beam radiotherapy, termed stereotactic body radiotherapy (SBRT), is able to emulate the doses and outcomes of HDR brachytherapy while being a noninvasive technique that employs commonly available radiotherapy equipment. All participants in this study will receive SBRT and be monitored for up to five years. in order to evaluate treatment toxicity, feasibility and efficacy.
Trial website
not applicable
Trial related presentations / publications
not applicable
Public notes

Contacts
Principal investigator
Name 54978 0
Dr Mark Sidhom
Address 54978 0
Liverpool Hospital
Corner of Elizabeth and Goulburn Sts
Liverpool
New South Wales 2170, Australia
Country 54978 0
Australia
Phone 54978 0
+61 (0)2 8738 9805
Fax 54978 0
+61 (0)2 8738 9819
Email 54978 0
Mark.Sidhom@health.nsw.gov.au
Contact person for public queries
Name 54979 0
A/Prof Jarad Martin
Address 54979 0
Calvary Mater Newcastle
Edith St
Waratah, Newcastle
New South Wales 2298, Australia
Country 54979 0
Australia
Phone 54979 0
+61 (0)2 4921 1211
Fax 54979 0
Email 54979 0
Jarad.Martin@calvarymater.org.au
Contact person for scientific queries
Name 54980 0
A/Prof Jarad Martin
Address 54980 0
Calvary Mater Newcastle
Edith St
Waratah, Newcastle
New South Wales 2298, Australia
Country 54980 0
Australia
Phone 54980 0
+61 (0)2 4921 1211
Fax 54980 0
Email 54980 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
Data will be analysed to show trends within the cohort.
What supporting documents are/will be available?
No other documents available
Summary results
No Results