Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000371796
Ethics application status
Approved
Date submitted
9/02/2022
Date registered
3/03/2022
Date last updated
30/08/2022
Date data sharing statement initially provided
3/03/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Personalised liver stereotactic body radiation therapy using magnetic resonance imaging for liver cancer
Scientific title
Personalised Liver Stereotactic Body Radiation Therapy using Magnetic Resonance Imaging for liver cancer: A Feasibility Study
Secondary ID [1] 306387 0
None
Universal Trial Number (UTN)
Trial acronym
PRISM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
hepatocellular carcinoma 325214 0
liver metastases 325215 0
Condition category
Condition code
Cancer 322616 322616 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participants will undergo Liver SBRT as standard of care. Interventions include liver Magnetic Resonance Imaging (MRI) scans and Indocyanine Green (ICG) blood tests at three time-points - before, during and 3 months after SBRT.

All participants will undergo safety screening for liver MRI scans and ICG tests.

ICG tests - ICG tests will be performed prior to the MRI scan. ICG will be administered as a bolus dose injection of 0.5mg/kg through an intra-venous cannula inserted by a trained nurse. The ICG will be reconstituted with 5ml of water for every 25mg of ICG, leading to a dilution of 5mg ICG per 1ml. Serial transcutaneous ICG measurements will then be taken for 20 minutes using an ICG clearance meter using a finger clip device (LiMON, Pulsion, Germany). The device automatically calculates and displays ICG clearance rates from the serial measurements, which will be recorded on the participant’s electronic case report form (CRF). Participants will lie in the supine position and calibration will be performed before testing starts. Total time taken for ICG tests will be around 30-40 minutes.

MRI scans - MRI scanning will be performed on a 3 Tesla MRI scanner by trained research radiographers as per the trial MRI Acquisition Guidelines. The MRI scan will include the injection of the standard clinical dose of MRI contrast agent Gadoxetate (Primovist, Bayer, Germany). The same intra-venous cannula, used for ICG testing, will be used for contrast agent injection, unless a new catheter is required. Primovist will be injected at the standard clinical dose of 0.1 mL/kg of patient body weight (equivalent to 0.025 mmol/kg). Patient body weight will be measured prior to each MRI scan. Injection will be performed by a power injector to obtain a constant injection rate and will be timed by the radiographer to occur just after the DCE-MRI acquisition is started. The MRI scan will be performed in the supine position and will take a maximum of one hour in total, including time for setup. The participant will be asked to remain still throughout the duration of the scan.

SBRT treatment will remain standard of care and will not be affected by the MRI and ICG results. The MRI and ICG data will be used to create liver function based SBRT (PRISM) treatment plans for study purposes.
Intervention code [1] 322821 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 330407 0
Feasibility of MRI based SBRT planning -
The proportion of participants for whom the dose to gross tumour volume (GTV) in PRISM based plans is higher than the dose to GTV in conventional SBRT plans
a) with no mid-treatment adaptation of PRISM plans
b) with mid-treatment adaptation of PRISM plans

This outcome will be determined by comparison of the dose delivered to GTV in standard SBRT plans with the prescribed dose to GTV in PRISM plans. Standard of care SBRT plans will be obtained from the participant's medical treatment records.
Timepoint [1] 330407 0
At the end of the study
Secondary outcome [1] 406255 0
Change in spatial liver function, as obtained from the MRI, compared to pre-treatment timepoints
Timepoint [1] 406255 0
Measured at mid-treatment (after 3 fractions of SBRT if 5-fraction scheme or after 2 fractions if 3-fraction scheme) and 3 months post-treatment (after the end of SBRT treatment) timepoints

Eligibility
Key inclusion criteria
• Aged 18 years or older
• Clinically (diagnostic MRI) or histologically diagnosed with HCC or liver metastases
• Has provided written informed consent for participation in this trial
• ECOG performance status 0-2
• Life expectancy > 6 months
• HCC patients with liver cirrhosis must be Child-Pugh A or B7-8 within 6 weeks prior to study entry
• Suitable and consented for liver SBRT
• Unsuitable for RFA or resection or transplant
• Willing and able to undergo repeated MRI scans with Primovist and ICG tests
• Screened for MRI safety as per local policy
• Participants capable of childbearing are using adequate contraception and will do so throughout trial participation
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• For HCC patients - Evidence of metastatic disease including nodal or distant metastases
• Cholangiocarcinoma
• Previous radiation to the liver (including SIRTEX)
• Has a known history of untreated HIV or active hepatitis B/C (no testing is required unless mandated by local health authority)
• Pregnant or lactating women
• On systemic therapy within 7 days before inclusion
• Contraindications to MRI
• Contraindications to ICG (participants will only be excluded from ICG tests, but can be eligible for the trial)

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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
This is an exploratory pilot study and, as such, formal sample size calculations have not been performed. However, it is anticipated that a sample size of at least 30 participants (based on pragmatic considerations) would provide sufficient numbers to obtain estimates of outcome parameters with reasonable precision. Fewer patients present with HCC than liver metastases, therefore, the number of liver metastases participants is capped at 10 to allow recruitment of HCC patients with a range of reduced liver function (CP-A, B7, and B8). This is a feasibility study designed in three stages, recruiting 5 participants in Stage 1, 10 participants in Stage 2 and 15 participants in Stage 3.

Stage 1 Analysis - Details of the study, including technical details of the imaging protocol will be reviewed to maximise the likelihood that participants in subsequent stages will complete all study assessments, and that the imaging data is optimised for liver function measurements.

Stage 2 Analysis - After a further 10 enrolled participants have completed their final post-treatment MRI scan, if a relationship between delivered treatment dose and liver function cannot be identified for at least half (5 or more) of the 10 participants, consideration will be given to determine the cause and the trial will be re-designed. If the results are positive, 15 additional participants will be accrued (Stage 3) for a total of 30 participants.

Final Analysis - At the end of Stage 3, a relationship between the delivered treatment dose and liver function will be developed using data collected from all participants in stages 2 and 3 of the study. PRISM based SBRT plans will be developed with and without mid-treatment adaptation, and dose to the GTV will be compared in each case with the dose delivered using conventional SBRT plans. The dose-liver function relationship will also be used to develop a predictive model of liver function.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2022
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 21687 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 36733 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 310742 0
Other Collaborative groups
Name [1] 310742 0
Sydney West Radiation Oncology Network
Country [1] 310742 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
Camperdown NSW 2006
Country
Australia
Secondary sponsor category [1] 311965 0
None
Name [1] 311965 0
Address [1] 311965 0
Country [1] 311965 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310317 0
Western Sydney Local Health District HREC
Ethics committee address [1] 310317 0
Ethics committee country [1] 310317 0
Australia
Date submitted for ethics approval [1] 310317 0
16/02/2022
Approval date [1] 310317 0
13/05/2022
Ethics approval number [1] 310317 0

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

Contacts
Principal investigator
Name 117230 0
Dr Sirisha Tadimalla
Address 117230 0
604 A28 Physics Rd
University of Sydney
Camperdown NSW 2006
Country 117230 0
Australia
Phone 117230 0
+61 406336005
Fax 117230 0
Email 117230 0
sirisha.tadimalla@sydney.edu.au
Contact person for public queries
Name 117231 0
Sirisha Tadimalla
Address 117231 0
604 A28 Physics Rd
University of Sydney
Camperdown NSW 2006
Country 117231 0
Australia
Phone 117231 0
+61 406336005
Fax 117231 0
Email 117231 0
sirisha.tadimalla@sydney.edu.au
Contact person for scientific queries
Name 117232 0
Sirisha Tadimalla
Address 117232 0
604 A28 Physics Rd
University of Sydney
Camperdown NSW 2006
Country 117232 0
Australia
Phone 117232 0
+61 406336005
Fax 117232 0
Email 117232 0
sirisha.tadimalla@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
SourceTitleYear of PublicationDOI
EmbaseRole of Functional MRI in Liver SBRT: Current Use and Future Directions.2022https://dx.doi.org/10.3390/cancers14235860
N.B. These documents automatically identified may not have been verified by the study sponsor.