Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000919617p
Ethics application status
Submitted, not yet approved
Date submitted
3/08/2023
Date registered
28/08/2023
Date last updated
28/08/2023
Date data sharing statement initially provided
28/08/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Magnetic Resonance (MR) Linear Accelerator (linac) prostate radiotherapy trial
Scientific title
A clinical trial exploring MR guided adaptive stereotactic radiotherapy boost to the prostate combined with stereotactic radiotherapy to the whole pelvis
Secondary ID [1] 310291 0
N/A
Universal Trial Number (UTN)
Trial acronym
MR-PROTEUS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 330994 0
Condition category
Condition code
Cancer 327805 327805 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Stereotactic pelvic radiotherapy combined with dose escalation to the prostate via a Stereotactic Body Radiotherapy (SBRT) boost will be delivered using an magnetic resonance (MR) Linear Accelerator (Linac). Participants will be randomised to receive either:

Arm 1:
Prostate SBRT: 10Gy per fraction in 2 treatments, 1 fraction per week (a minimum of 7 and a maximum of 11 days apart) delivered before pelvic SBRT.

Pelvic SBRT: 25Gy in 5 fractions (5Gy per fraction), 1 fraction per week over 5 weeks. Should commence between 7 to 11days after the second SBRT fraction.


Arm 2:
Prostate SBRT: 10Gy per fraction in 1 treatment 7 to 11 days before pelvic SBRT and 10Gy per fraction in 1 treatment 7 to 11 days after pelvic SBRT.

Pelvic SBRT: 25Gy in 5 fractions (5Gy per fraction) treated weekly over 5 weeks. Should commence between 7 to 11 days after the first SBRT fraction.

Trial radiotherapy will be delivered by radiation therapists under the direction of the treating radiation oncologist according to the research protocol and standard clinical operating procedures of the clinic. Each SBRT treatment will take approximately 40 minutes.
Intervention code [1] 326675 0
Treatment: Other
Comparator / control treatment
Both treatment arms in this trial are investigational. For the purposes of this record, the comparator arm is Arm 2 which consists of:

Prostate SBRT: 10Gy per fraction in 1 treatment 7 to 11 days before pelvic SBRT and 10Gy per fraction in 1 treatment 7 to 11 days after pelvic SBRT.

Pelvic SBRT: 25Gy in 5 fractions (5Gy per fraction) treated weekly over 5 weeks. Should commence between 7 to 11 days after the first SBRT fraction.
Control group
Active

Outcomes
Primary outcome [1] 335654 0
Feasibility of stereotactic pelvic radiotherapy combined with stereotactic dose escalation to the prostate via an MR-Linac assessed by study accrual determined from trial records.
Timepoint [1] 335654 0
To be assessed following completion of study accrual and treatment of the last enrolled participant
Primary outcome [2] 335655 0
To determine the safety of using MR-Linac for stereotactic radiotherapy to the pelvis and dose escalation to the prostate via a SBRT boost. Known possible adverse events include constipation, erectile dysfunction, diarrhoea, fatigue, faecal incontinence, proctitis, rectal haemhorrage, rectal mucositis, rectal pain, non-infective cystitis, urinary frequency, urinary retention, urinary incontinence, urinary tract pain, urinary urgency. These will be assessed by the investigator during clinical examination and interview with the participant.
Timepoint [2] 335655 0
Participants will be followed up for 3 years following end of study treatment for adverse events.
Primary outcome [3] 335656 0
To assess if the proposed 2 arm boost design of MR-guided SBRT is safe. Known possible adverse events include constipation, erectile dysfunction, diarrhoea, fatigue, faecal incontinence, proctitis, rectal haemhorrage, rectal mucositis, rectal pain, non-infective cystitis, urinary frequency, urinary retention, urinary incontinence, urinary tract pain, urinary urgency. These will be assessed by the investigator during clinical examination and interview with the participant.
Timepoint [3] 335656 0
Participants will be followed up for 3 years following end of study treatment for adverse events.
Secondary outcome [1] 425108 0
Primary Outcome: To assess if there are meaningful differences in toxicity when comparing the 2 treatment arms. Known possible adverse events include constipation, erectile dysfunction, diarrhoea, fatigue, faecal incontinence, proctitis, rectal haemhorrage, rectal mucositis, rectal pain, non-infective cystitis, urinary frequency, urinary retention, urinary incontinence, urinary tract pain, urinary urgency. These will be assessed by the investigator during clinical examination and interview with the participant.
Timepoint [1] 425108 0
Participants will be followed up for 3 years following end of study treatment for adverse events.
Secondary outcome [2] 425109 0
To assess participants’ quality of life using patient reported outcomes using IPSS.
Timepoint [2] 425109 0
Patient reported outcomes will be completed at Baseline, End of Treatment, 6-weeks post radiotherapy, 3 monthly thereafter for 12 months, at 18 months, 2 years and 3 years post radiotherapy.
Secondary outcome [3] 425110 0
To assess if there is a meaningful change in the size of the dominant intraprostatic lesion (DIL) values when comparing the 2 arms. This will be assessed using MRI imaging from the MR-linac.
Timepoint [3] 425110 0
This will be assessed using MRIs generated at each radiotherapy fraction.
Secondary outcome [4] 425741 0
To assess if there is a meaningful change in the size of the Apparent Diffusion Coefficient (ADC) values when comparing the 2 arms. This will be assessed using MRI imaging from the MR-linac.
Timepoint [4] 425741 0
This will be assessed using MRIs generated at each radiotherapy fraction.
Secondary outcome [5] 425757 0
Primary outcome: Feasibility of stereotactic pelvic radiotherapy combined with stereotactic dose escalation to the prostate via an MR-Linac assessed by successful treatment planning determined from planning records.
Timepoint [5] 425757 0
To be assessed following completion of study accrual and treatment of the last enrolled participant
Secondary outcome [6] 425758 0
Primary Outcome: Feasibility of stereotactic pelvic radiotherapy combined with stereotactic dose escalation to the prostate via an MR-Linac assessed by successful treatment delivery determined from radiotherapy records
Timepoint [6] 425758 0
To be assessed following completion of study accrual and treatment of the last enrolled participant
Secondary outcome [7] 426007 0
To assess participants’ quality of life using patient reported outcomes using IIEF-5.
Timepoint [7] 426007 0
Patient reported outcomes will be completed at Baseline, End of Treatment, 6-weeks post radiotherapy, 3 monthly thereafter for 12 months, at 18 months, 2 years and 3 years post radiotherapy.
Secondary outcome [8] 426008 0
To assess participants’ quality of life using patient reported outcomes using EORTC QLQ-C30.
Timepoint [8] 426008 0
Patient reported outcomes will be completed at Baseline, End of Treatment, 6-weeks post radiotherapy, 3 monthly thereafter for 12 months, at 18 months, 2 years and 3 years post radiotherapy.
Secondary outcome [9] 426009 0
To assess participants’ quality of life using patient reported outcomes using\ EORTC QLQ-PR25.
Timepoint [9] 426009 0
Patient reported outcomes will be completed at Baseline, End of Treatment, 6-weeks post radiotherapy, 3 monthly thereafter for 12 months, at 18 months, 2 years and 3 years post radiotherapy.
Secondary outcome [10] 426010 0
To assess participants’ quality of life using patient reported outcomes using EQ-5D-5l.
Timepoint [10] 426010 0
Patient reported outcomes will be completed at Baseline, End of Treatment, 6-weeks post radiotherapy, 3 monthly thereafter for 12 months, at 18 months, 2 years and 3 years post radiotherapy.

Eligibility
Key inclusion criteria
1. Patient capable of giving informed consent
2. Histological diagnosis of prostate cancer
3. Intermediate or High-risk disease respectively defined by any one of:
a. Baseline Prostate Specific Antigen (PSA) 10-20, Gleason grade 7 disease, Clinical stage T2b-c OR
b. Baseline PSA equal to or more than 20, Gleason grade 8-10 disease, Clinical stage T3
4. For high-risk patients, conventional staging (in the form of any of the below) negative for extra pelvic disease:
a. PSMA PET scan OR
b. Tc99m whole body bone scan AND
c. 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?
No
Key exclusion criteria
1. ECOG performance status more than 1
2. Inability to have an MRI due to:
a. Implanted magnetic metal eg intraocular metal
b. Pacemaker or Implantable defibrillator
c. Extreme claustrophobia
3. Clinical stage T4 (tumour invasion into adjacent anatomical structures)
4. Inflammatory bowel disease
5. Severe obstructive urinary symptoms
6. Inability to meet planning objectives
7. Severe Claustrophobia
8. Contraindication to 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)
Computer generated central randomisation using the electronic data capture (EDC) system
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using computer generated sequence
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis
The primary outcome of safety will be determined by the overall rates of grade 2 or higher GI and GU toxicity. In the acute setting, a combined GI / GU toxicity rate of 60% is in accordance with acceptable practice, whereas 75% or higher would be concerning. In the late setting, a combined GI / GU toxicity rate of 33% is in accordance with acceptable practice, whereas 50% or higher would be concerning. To evaluate both acute and late settings with 80% power, 5% one-sided significance level and allowance for 10% loss to follow-up, we will need to recruit a sample size of 68 participants for this study.

They will be randomised in a 1:1 ratio between Arm 1: prostate SBRT (20 Gy/2 fractions) followed by pelvic SBRT and Arm 2: prostate SBRT (10 Gy/1 fraction) before and after pelvic SBRT. Randomisation will be computer-generated to ensure allocation concealment.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2023
Actual
Date of last participant enrolment
Anticipated
1/10/2026
Actual
Date of last data collection
Anticipated
1/10/2029
Actual
Sample size
Target
68
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 25326 0
GenesisCare - St. Vincent's Sydney - Darlinghurst
Recruitment hospital [2] 25327 0
GenesisCare - Murdoch - Murdoch
Recruitment postcode(s) [1] 41030 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 41031 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 314502 0
Commercial sector/Industry
Name [1] 314502 0
Eletka
Country [1] 314502 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
GenesisCare
Address
Building 7C & D,
Level 1, The Mill,
41-43 Bourke Road
Alexandria NSW 2015
Country
Australia
Secondary sponsor category [1] 316449 0
None
Name [1] 316449 0
Address [1] 316449 0
Country [1] 316449 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 313548 0
St Vincent's Hospital Sydney HREC
Ethics committee address [1] 313548 0
Ethics committee country [1] 313548 0
Australia
Date submitted for ethics approval [1] 313548 0
31/07/2023
Approval date [1] 313548 0
Ethics approval number [1] 313548 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 128506 0
Dr Jeremy de Leon
Address 128506 0
GenesisCare St Vincent's Sydney
Level A, 438 Victoria Street, Darlinghurst, 2020 NSW
Country 128506 0
Australia
Phone 128506 0
+61 2 8302 5400
Fax 128506 0
Email 128506 0
[email protected]
Contact person for public queries
Name 128507 0
Kathryn Hogan
Address 128507 0
GenesisCare
Building 7C & D,
Level 1, The Mill,
41-43 Bourke Road
Alexandria NSW 2015
Country 128507 0
Australia
Phone 128507 0
+61 0456999676
Fax 128507 0
Email 128507 0
[email protected]
Contact person for scientific queries
Name 128508 0
Kathryn Hogan
Address 128508 0
GenesisCare
Building 7C & D,
Level 1, The Mill,
41-43 Bourke Road
Alexandria NSW 2015
Country 128508 0
Australia
Phone 128508 0
+61 0456999676
Fax 128508 0
Email 128508 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Participant consent does not allow for sharing of IPD


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.