ANZCTR - Registration

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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

5/11/2023

Date data sharing statement initially provided

16/09/2019

Date results information initially provided

19/05/2021

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]

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

Condition category

Condition code

Cancer

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]

Treatment: Devices

Intervention code [2]

Treatment: Other

Comparator / control treatment

Not applicable

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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]

End of study

Primary outcome [2]

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]

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]

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]

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]

Cancer control assessed by biochemical response and freedom from clinical signs of tumour recurrence.

Timepoint [2]

Assessed at six weeks after radiotherapy, and then at six monthly intervals for three years then annually for another two years.

Secondary outcome [3]

Prostate motion assessed by MRI scans, and real time imaging during radiotherapy of prostate position.

Timepoint [3]

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

Sex

Males

Can healthy volunteers participate?

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

Completed

Date of first participant enrolment

Anticipated

1/11/2013

Actual

3/03/2014

Date of last participant enrolment

Anticipated

31/12/2019

Actual

21/11/2018

Date of last data collection

Anticipated

31/12/2024

Actual

28/02/2023

Sample size

Target

150

Accrual to date

Final

129

Recruitment in Australia

Recruitment state(s)

NSW,QLD

Recruitment hospital [1]

Calvary Mater Newcastle - Waratah

Recruitment hospital [2]

Liverpool Hospital - Liverpool

Recruitment hospital [3]

Campbelltown Hospital - Campbelltown

Recruitment hospital [4]

St George Hospital - Kogarah

Recruitment hospital [5]

Princess Alexandra Hospital - Woolloongabba

Recruitment hospital [6]

Mater Adult Hospital - South Brisbane

Recruitment postcode(s) [1]

2298 - Waratah

Recruitment postcode(s) [2]

2170 - Liverpool

Recruitment postcode(s) [3]

2560 - Campbelltown

Recruitment postcode(s) [4]

2217 - Kogarah

Recruitment postcode(s) [5]

4102 - Woolloongabba

Recruitment postcode(s) [6]

4101 - South Brisbane

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Address [1]

Country [1]

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]

Individual

Name [1]

A/Prof Jarad Martin

Address [1]

Calvary Mater Hospital Newcastle
Edith St
Waratah, Newcastle
New South Wales 2298, Australia

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

South Western Sydney Local Health District

Ethics committee address [1]

Research and Ethics Office
Locked Bag 7103
Liverpool BC
NSW 2871

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

02/12/2013

Ethics approval number [1]

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

Dr Mark Sidhom

Address

Liverpool Hospital
Corner of Elizabeth and Goulburn Sts
Liverpool
New South Wales 2170, Australia

Country

Australia

Phone

+61 (0)2 8738 9805

Fax

+61 (0)2 8738 9819

[email protected]

Contact person for public queries

Name

A/Prof Jarad Martin

Address

Calvary Mater Newcastle
Edith St
Waratah, Newcastle
New South Wales 2298, Australia

Country

Australia

Phone

+61 (0)2 4921 1211

Fax

[email protected]

Contact person for scientific queries

Name

A/Prof Jarad Martin

Address

Calvary Mater Newcastle
Edith St
Waratah, Newcastle
New South Wales 2298, Australia

Country

Australia

Phone

+61 (0)2 4921 1211

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Data will be analysed to show trends within the cohort.

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Study results article	Yes		Legge K, Nguyen D, Ng JA, Wilton L, Richardson M, ... [More Details]
Study results article	Yes		Asia Pacific Journal of Clinical Oncology: Special... [More Details]

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Rectal protection in prostate stereotactic radiotherapy: a retrospective exploratory analysis of two rectal displacement devices.	2017	https://dx.doi.org/10.1002/jmrs.238
Embase	Reduced motion and improved rectal dosimetry through endorectal immobilization for prostate stereotactic body radiotherapy.	2019	https://dx.doi.org/10.1259/bjr.20190056
Embase	Stereotactic Body Radiation Therapy and High-Dose-Rate Brachytherapy Boost in Combination With Intensity Modulated Radiation Therapy for Localized Prostate Cancer: A Single-Institution Propensity Score Matched Analysis.	2021	https://dx.doi.org/10.1016/j.ijrobp.2020.12.034
Embase	Reducing ExacTrac intrafraction imaging uncertainty for prostate stereotactic body radiotherapy using a pre-treatment CBCT.	2022	https://dx.doi.org/10.1007/s13246-022-01121-7
Dimensions AI	Prostate Virtual High-dose-rate Brachytherapy Boost: 5-Year Results from the PROMETHEUS Prospective Multicentre Trial	2024	https://doi.org/10.1016/j.euo.2024.01.008
Dimensions AI	Phase 2 Multicenter Study of Gantry-Based Stereotactic Radiotherapy Boost for Intermediate and High Risk Prostate Cancer (PROMETHEUS)	2019	https://doi.org/10.3389/fonc.2019.00217
Dimensions AI	PROstate Multicentre External beam radioTHErapy Using a Stereotactic boost: the PROMETHEUS study protocol	2018	https://doi.org/10.1186/s12885-018-4511-6
Dimensions AI	PO-0822: Patient-reported outcomes after hypofractionated radiotherapy to 66Gy for prostate cancer	2018	https://doi.org/10.1016/s0167-8140(18)31132-0
Dimensions AI	PO-0823: TRAC: Automated atlas based machine learning QA of contouring accuracy for the PROMETHEUS trial	2018	https://doi.org/10.1016/s0167-8140(18)31133-2
Dimensions AI	EP-1541 Intention to treat analysis of 68Ga-PSMA/11Ccholine PET/CT vs. CT for prostate cancer recurrences	2019	https://doi.org/10.1016/s0167-8140(19)31961-9
Dimensions AI	PO-0821: Radiation-induced late rectal toxicity for IMPT vs VMAT in patients with localized prostate cancer	2018	https://doi.org/10.1016/s0167-8140(18)31131-9

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically