Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001372774
Ethics application status
Approved
Date submitted
3/12/2021
Date registered
26/10/2022
Date last updated
26/10/2022
Date data sharing statement initially provided
26/10/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Feasibility study of delayed neurosurgical resection following pre-operative stereotactic radiosurgery for non-small cell lung cancer and melanoma brain metastases
Scientific title
PRISM: PRobing the Immunological Impact of Stereotactic Radiosurgery for Brain Metastases
Secondary ID [1] 305965 0
None
Universal Trial Number (UTN)
Trial acronym
PRISM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Brain metastases 324565 0
Non-small cell lung cancer 324757 0
Melanoma 324758 0
Condition category
Condition code
Cancer 322033 322033 0 0
Brain
Cancer 322209 322209 0 0
Lung - Non small cell
Cancer 322210 322210 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single arm study examining the feasibility of neurosurgical resection 7-21 days following completion of pre-operative stereotactic radiosurgery (SRS) for brain metastases (BMs), where clinically appropriate. This is in contrast to the current practice where there is no standardised time frame between SRS and neurosurgery. Translational blood and tumour tissue will also be obtained.

1. Stereotactic radiosurgery (SRS)
SRS is a highly precise form of radiation therapy (RT) that delivers high doses of radiation in a few treatment fractions (typically 20-25Gy in 1-5 fractions) to individual BM tumours while sparing the surrounding normal brain tissue. For the patient this will involve first a planning CT scan as an outpatient, followed by 1-5 daily outpatient treatment visits to the Peter MacCallum Cancer Centre. Each treatment session will take approximately 30 minutes, depending on the number and size of lesions treated. This treatment is non-invasive and there will be no incision or general anaesthesia involved.

2. Neurosurgical resection of brain metastasis (BM)
Following completion of SRS treatment, neurosurgical resection of the BM will be scheduled to take place 7-21 days later. This will be performed at the Royal Melbourne Hospital and will involve a few days of hospital stay after the surgery (usually 2-4 days). The patient will be under general anaesthesia during the procedure, which lasts approximately 4-6 hours. During the hospital stay patient's are monitored regularly by the neurosurgeon and hospital staff.

3. Collection of translational tissue
Pre- and post-SRS bloods will be collected at 4 time points over 6 months, to coincide with routine follow-up appointments. The resected BM tissue will also be banked for research purposes. No additional resections or biopsies on top of standard of care treatments are necessary for this study. All specimens collected will be de-identified.

After treatment: Trial participants will be reviewed as part of the study at 1 week, 4 weeks, 3 months and 6 months after completion of SRS. MRI scans of the brain be organised at 3 months post SRS. This follow-up schedule is standard for all patients having SRS and neurosurgery.
Intervention code [1] 322357 0
Treatment: Other
Intervention code [2] 324671 0
Treatment: Surgery
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 329789 0
To assess the feasibility of a 7-21 day time window between pre-operative SRS and BM resection in patients with metastatic NSCLC or melanoma,

BM resection 7-21 days after pre-operative SRS will be considered feasible if resection within that timeframe is achieved for at least 66% of patients (at least 10 of 15 patients). This will be determined on a scheduled clinical assessments at 4 weeks post SRS.
Timepoint [1] 329789 0
4 weeks post SRS
Secondary outcome [1] 403778 0
Rate of surgical complication and acute radiation toxicity (as composite outcome)

These adverse events are graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Timepoint [1] 403778 0
1 week, 4 weeks, 3 month, and 6 months post SRS
Secondary outcome [2] 403779 0
Local control rate, as assessed by MRI brain
Timepoint [2] 403779 0
6 months post SRS
Secondary outcome [3] 414859 0
CNS progression-free survival, as assessed by clinical assessment and MRI brain
Timepoint [3] 414859 0
6 months post SRS
Secondary outcome [4] 414860 0
Leptomeningeal relapse rate, as assessed by MRI brain
Timepoint [4] 414860 0
6 months post SRS
Secondary outcome [5] 414861 0
Distant brain control rate, as assessed by MRI brain
Timepoint [5] 414861 0
6 months post SRS
Secondary outcome [6] 414862 0
Radionecrosis rate, as assessed by clinical assessment and MRI brain
Timepoint [6] 414862 0
6 months post SRS
Secondary outcome [7] 414863 0
Overall survival, as assessed by clinical assessment
Timepoint [7] 414863 0
6 months post SRS

Eligibility
Key inclusion criteria
• Aged 18 years or older
• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) or melanoma
• Brain metastases (BMs) confirmed on MRI – there is no limit on the number or size of BM(s) planned for SRS; only one irradiated BM needs to be resected, at least
• ECOG performance status 0-2
• Suitable for treatment with combined SRS and neurosurgery
• Suitable for collection of peripheral blood
• Be able to provide written Informed Consent for participation in this study
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Previous intracranial RT (WBRT or SRS)
PRISM Protocol Version 1.0 Page 13 of 32
• Need for urgent BM resection for relief of mass effect or symptoms (as per clinician judgment)
• Steroid requirement of dexamethasone > 4 mg/day or equivalent
• Diffuse leptomeningeal disease
• Planned (adjuvant) WBRT after SRS
• Pregnant or breastfeeding

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
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/01/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
15
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 21268 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 36139 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 310307 0
Commercial sector/Industry
Name [1] 310307 0
Varian Medical Systems Australasia
Country [1] 310307 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Center
Address
305 Grattan Street
Melbourne VIC 3000
Country
Australia
Secondary sponsor category [1] 311428 0
None
Name [1] 311428 0
Address [1] 311428 0
Country [1] 311428 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309970 0
Peter MacCallum Cancer Centre Human Research Ethics Committee
Ethics committee address [1] 309970 0
Ethics committee country [1] 309970 0
Australia
Date submitted for ethics approval [1] 309970 0
03/12/2021
Approval date [1] 309970 0
19/08/2022
Ethics approval number [1] 309970 0
HREC/81713/PMCC

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

Contacts
Principal investigator
Name 116026 0
Dr Joseph Sia
Address 116026 0
Department of Radiation Oncology
Peter MacCallum Cancer Center
305 Grattan Street
Melbourne VIC 3000
Country 116026 0
Australia
Phone 116026 0
+61 3 85597993
Fax 116026 0
Email 116026 0
[email protected]
Contact person for public queries
Name 116027 0
Joseph Sia
Address 116027 0
Department of Radiation Oncology
Peter MacCallum Cancer Center
305 Grattan Street
Melbourne VIC 3000
Country 116027 0
Australia
Phone 116027 0
+61 3 85597993
Fax 116027 0
Email 116027 0
[email protected]
Contact person for scientific queries
Name 116028 0
Joseph Sia
Address 116028 0
Department of Radiation Oncology
Peter MacCallum Cancer Center
305 Grattan Street
Melbourne VIC 3000
Country 116028 0
Australia
Phone 116028 0
+61 3 85597993
Fax 116028 0
Email 116028 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
After data de-identification, all of the individual participant data collected during the trial may be made available to eligible and approved researchers. These data will include date of treatments received, size of brain metastases treated, concurrent medications, and clinical and toxicity outcomes.
When will data be available (start and end dates)?
Data may be made available on request within 15 years after publication of the study results (expected by 2026).
Available to whom?
Data will only be made available to researchers who provide a methodologically sound proposal, on case-by-case basis at the discretion of Principal Investigator and Human Research Ethics Committee.
Available for what types of analyses?
Data may only be made available to achieve the aims of an approved proposal or IPD meta-analyses.
How or where can data be obtained?
Expressions of interest relating to future data access can be made to the Principal Investigator ([email protected]; +61 3 85597993)


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.