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Trial registered on ANZCTR


Registration number
ACTRN12615000335594
Ethics application status
Approved
Date submitted
9/03/2015
Date registered
14/04/2015
Date last updated
10/12/2019
Date data sharing statement initially provided
10/12/2019
Date results information initially provided
10/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
TROG 15.01 (SPARK) Efficacy of Kilovoltage Intrafraction Monitoring (KIM) in men with prostate cancer undergoing stereotactic prostate radiotherapy
Scientific title
TROG 15.01: Efficacy of Kilovoltage Intrafraction Monitoring (KIM) in Stereotactic Prostate Adaptive Radiotherapy on clinical outcomes and toxicity in prostate cancer patients (SPARK)
Secondary ID [1] 286331 0
Nil
Universal Trial Number (UTN)
U1111-1167-3258
Trial acronym
SPARK
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 294438 0
Condition category
Condition code
Cancer 294743 294743 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participants will receive Multi-Fraction SABR; 36.25 Gy (PTV D95) in 5 Fractions within 2-5 weeks.
The frequency and overall duration of SABR is determined at the discretion of the physician with patient consultation.
Most linear accelerators used to treat cancer patients today are equipped with fixed X-ray imagers which are typically used to take images of a tumour before a patient receives radiotherapy. A new technology, known as Kilovoltage Intrafraction Monitoring (KIM), has recently emerged which allows images the position of a the tumour to be taken measured in real-time while the treatment is occurring. Real-time imaging involves a single gantry-mounted kV x-ray imager acquiring 2D projections of implanted fiducial markers. 3D positions are then reconstructed by maximum likelihood estimation of a 3D probability density function.
The SPARK trial is testing the use of KIM in prostate cancer patients being treated with Stereotactic Prostate Adaptive Radiotherapy. The researchers expect this trial to result in better targeted prostate cancer patient outcomes with lower toxicity.
Patients involved in this trial will receive radiotherapy to the prostate over five sessions given within two weeks. During radiation therapy, KIM will be used to check the position of the cancer. If the cancer moves more than 3mm, the treatment will be stopped and the cancer will be realigned with the treatment beam. The five stereotactic sessions will take around one hour each, including the preparation time.
From the end of treatment participants will be followed up at regular intervals for the reminder of the study, which will be a minimum of 2 years from enrolment.
Intervention code [1] 291380 0
Treatment: Devices
Intervention code [2] 291450 0
Treatment: Other
Comparator / control treatment
This is not a controlled study in the sense of having an independent non-treated cohort. The patients are their own control.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 294507 0
A dose accumulation method will be used to determine the efficacy of KIM, where the isodose distributions and dose volume histograms for each session will be calculated with Kilovoltage Intrafraction Monitoring (KIM) corrections as treated, and estimated without KIM corrections
Timepoint [1] 294507 0
After all patients have completed their final SABR treatment session
Secondary outcome [1] 313486 0
The main efficacy endpoint will be biochemical-clinical failure (BCF). This is a hybrid event, with any of the following counting towards BCF:
1. PSA relapse - using the Phoenix definition, any rise in the PSA >2ng/L above the nadir will count as a biochemical relapse.
2. Local failure - repeat prostate biopsy at least 2 years after completion of treatment and showing viable cancer cells as assessed by an expert in genitourinary pathology.
3. Distant failure – Either new nodal lesions or bone metastases will count as an event only if confirmed to be due to prostate cancer on biopsy if occurring in the absence of a rising PSA.
4. Initiation of salvage androgen deprivation therapy (ADT) – In the absence of any of the above events.
Timepoint [1] 313486 0
The time to BCF will be the period from registration to the event
Secondary outcome [2] 313487 0
Patient treatment outcomes determined by assessing acute and late toxicity grade 3 or higher (using CTCAE version 4)
Timepoint [2] 313487 0
Weekly during treatment, then two weeks, six weeks and 6 months post treatment
Secondary outcome [3] 313488 0
Patient reported outcomes will use the Expanded Prostate Cancer Index Composite (EPIC) questionnaire, an instrument that assesses a broad spectrum of bowel, urinary, sexual and hormonal symptoms
Timepoint [3] 313488 0
12 and 24 months after treatment
Secondary outcome [4] 313489 0
Radiation therapist’s feedback on KIM will be quantified using an anonymous radiation therapist survey, designed specifically for this study, which will obtain specific information about the impact of the KIM system and SPARK on many relevant fronts to radiation therapy practice, including education, patient workflow, clinical impact and user confidence.
Timepoint [4] 313489 0
At the end of the patients SABR treatment session
Secondary outcome [5] 313490 0
Targeting accuracy through measuring the difference in each of the 3 orthogonal planes of prostate position from the starting position with and without the KIM guided gating procedure. The position without KIM will be estimated by adding any couch shifts performed during treatment to any deviations noted at the end of each treatment.
Timepoint [5] 313490 0
After all patients have completed their final SABR treatment session
Secondary outcome [6] 313693 0
The patient’s perception of KIM will be quantified using an adapted SAT-RAR survey, an instrument that assessed patient perceptions on technological innovations in radiotherapy and respiratory gating.
Timepoint [6] 313693 0
At the end of the patients SABR treatment session

Eligibility
Key inclusion criteria
1. Histologically proven prostate adenocarcinoma
2. Low or intermediate risk disease as defined by:
- Low Risk: All of PSA<10 ng/mL, Gleason Grade 6 AND Stage T1 or T2a
- Intermediate Risk: Any or all of PSA 10-20 ng/mL, Gleason Grade 7 OR Stage T2b-c
- Absence of high risk features (PSA>20, T3-4, N1 or M1 disease, Gleason score 8-10)
(PSA must be within 3 months prior to enrolment)
3. ECOG Performance status 0-2
4. Suitable for definitive external beam radiotherapy (IMRT or VMAT)
5. Ability to have three gold fiducial markers placed in the prostate*
6. Six month course of androgen deprivation therapy allowed at clinician discretion.
7. Available for follow up for a minimum of 2 years (up to 3 years)
*if on anticoagulants, must be approved for procedure
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Lymph node irradiation
2. Any other systemic anti-prostate cancer therapy (i.e. non-ADT) both proven in the metastatic setting and investigational (e.g. docetaxel, enzalutamide)
3. Artificial hip(s) (Unable to visualise markers through prosthesis)
4. Prostate volume > 90 cm3 measured from the CT scan
5. Patient lateral dimension >40cm as measured at the level of the prostate from the CT scan
6. Suboptimal fiducial markers placement for treatment utilising KIM as assessed by a medical physicist by measuring marker positions from the CT scan
7. Fiducial migration or fewer than 3 fiducials present in the CT scan

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/efficacy
Statistical methods / analysis
Accumulated patient dose distributions will be determined via paired controls by comparing the measured treatment accuracy and dose with Kilovoltage Intrafraction Monitoring (KIM) and those that would have been delivered in the absence of KIM. The estimated clinical benefit of the real-time KIM method will be determined using radiation biological response models.
For treatment sessions with interventions, the PTV D95 and the volume of rectum receiving >30Gy (V30) will be calculated with and without KIM corrections. We choose PTV D95 as the PTV margins are chosen to ensure dose coverage of the CTV with the majority of the uncertainty from contour delineation. In the absence of strong dose-volume correlates for prostate SBRT, we choose rectal V30 to scale the SBRT prescription dose approximately linearly with the conventional fractionation prescription dose. For conventional fractionation the volume of rectum receiving >60Gy (V60) is consistently associated with the risk of Grade >2 rectal toxicity or rectal bleeding.
We consider a treatment session with correction events a success if the KIM-corrected dose distribution has the PTV D95 and the rectal V30 closer to the planned values than the dose distribution estimated without KIM correction. We consider a treatment session with intervention events a failure if the PTV D95 or the rectal V30 are equal to or further from the planned values than the dose distribution estimated without KIM corrections.
If KIM can correct for these treatment failures in 2/3 (67%) or more of treatment sessions with interventions, KIM is beneficial. However if KIM can only correct for these treatment failures in 1/3 (33%) or fewer of these sessions, then KIM would be considered futile or ineffective, and other strategies to improve suboptimal treatments in prostate SBRT would be needed.
In this phase II exploratory design if we treat each treatment session as an independent event, which is a reasonable assumption based on the lack of predictability of prostate motion, then using Simon’s two-stage design with optimum design parameters a sample size of 24 sessions with intervention events will give us 90% power with 95% confidence to rule in a success rate of 2/3 in favour of the futile rate of 1/3. To obtain an estimated 24 treatment sessions with intervention events we need 24/0.10 = 240 treatment sessions, which for the 5-session SBRT regime means 48 patients. The null hypothesis will be rejected if 16 or more responses are observed in 48 patients. This design yields a type I error rate of 0.0488 and power of 0.91 when the true response rate is 67%.

Recruitment
Recruitment status
Active, not 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,VIC
Recruitment hospital [1] 4705 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [2] 4706 0
Westmead Hospital - Westmead
Recruitment hospital [3] 4707 0
Liverpool Hospital - Liverpool
Recruitment hospital [4] 4709 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [5] 8580 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 16687 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 290902 0
Government body
Name [1] 290902 0
Cancer Australia
Address [1] 290902 0
Level 14, 300 Elizabeth Street, Surry Hills NSW 2010
Country [1] 290902 0
Australia
Funding source category [2] 290903 0
Charities/Societies/Foundations
Name [2] 290903 0
Prostate Cancer Foundation of Australia
Address [2] 290903 0
Level 3, 39-41 Chandos St, St Leonards NSW 2065
Country [2] 290903 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
Level 6 Medical Foundation Building
92-94 Parramatta Road
The University of Sydney, NSW 2006
Country
Australia
Secondary sponsor category [1] 289584 0
None
Name [1] 289584 0
Address [1] 289584 0
Country [1] 289584 0
Other collaborator category [1] 278389 0
Other Collaborative groups
Name [1] 278389 0
Trans Tasman Radiation Oncology Group (TROG)
Address [1] 278389 0
TROG Central Office
Calvary Mater Newcastle
MHA Building, Level 5
Edith St
Waratah, NSW 2298
Country [1] 278389 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292505 0
The Hunter New England Human Research Ethics Committee
Ethics committee address [1] 292505 0
Research Ethics and Governance Unit
Hunter New England Local Health District
Locked Bag 1
New Lambton NSW 2305

Ethics committee country [1] 292505 0
Australia
Date submitted for ethics approval [1] 292505 0
20/05/2015
Approval date [1] 292505 0
19/06/2015
Ethics approval number [1] 292505 0
15/06/17/3.01

Summary
Brief summary
This study will determine the efficacy of the addition of Kilovoltage Intrafraction Monitoring during stereotactic prostate adaptive radiotherapy in prostate cancer patients.

Who is it for?
You may be eligible to join this study if you are aged 18 years or above and have histologically proven prostate adenocarcinoma with low or intermediate disease risk.

Study details
All participants will receive multi-fraction stereotactic prostate adaptive radiotherapy at 36.25 Gy in 5 fractions over 2-5 weeks. A new technology, known as Kilovoltage Intrafraction Monitoring (KIM), will be used which allows images of a tumour to be taken in real-time while the treatment is occurring. This enables strategies such as patient shifting or beam shifting during treatment which could potentially improve the accuracy of the treatment and reduce the patient’s side effects. In addition, due to the accuracy of KIM in targeting tumours, the number of treatment sessions this group of patients will require will be reduced to five as opposed to the 40 sessions required using more conventional treatment methods.

Efficacy of KIM will be assessed by the dose accumulation method for each session. Participants will be followed for up to 2 years, in order to determine patient treatment outcomes, and toxicity. The researchers expect this trial to result in better targeted prostate cancer patient outcomes with lower toxicity. The potential application of KIM to other tumour sites will pave the way for additional trials with Australasian radiation oncology leading the world.
Trial website
https://trog.com.au/TROG-1501-SPARK
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 55638 0
Prof Paul Keall
Address 55638 0
The University of Sydney
Room 474, Blackburn Building D06
Camperdown, 2006, NSW
Country 55638 0
Australia
Phone 55638 0
+61 2 93513590
Fax 55638 0
+61 2 9351 4018
Email 55638 0
paul.keall@sydney.edu.au
Contact person for public queries
Name 55639 0
Mrs Brita Lehmann
Address 55639 0
TROG Cancer Research
PO BOX 88, Waratah, NSW 2298
Country 55639 0
Australia
Phone 55639 0
+61 02 401 43911
Fax 55639 0
Email 55639 0
spark@trog.com.au
Contact person for scientific queries
Name 55640 0
A/Prof Jarad Martin
Address 55640 0
Department of Radiation Oncology
Calvary Mater Newcastle
Edith St
Waratah, NSW
2298
Country 55640 0
Australia
Phone 55640 0
+61 2 40143631
Fax 55640 0
Email 55640 0
Jarad.Martin@calvarymater.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary