Trial Review

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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12626000956303
Ethics application status
Help: Ethics application status
Approved
Date submitted
Help: Date submitted
11/07/2025
Date registered
Help: Date registered
4/08/2026
Date last updated
Help: Date last updated
4/08/2026
Date data sharing statement initially provided
Help: Data sharing statement date
4/08/2026
Type of registration
Help: Type of registration
Prospectively registered

Titles & IDs
Public title
SMART: Single and multi-fraction preoperative stereotactic radiosurgery (Pre-SRS) for patients with brain metastases
Scientific title
Single and multi-fraction preoperative stereotactic radiosurgery (Pre-SRS) - analysing 12 months cavity local control for patients with brain metastases
Additional trial identifiers [1] 314890 0
TROG 23.02
Universal Trial Number (UTN)
U1111-1307-5464
Trial acronym
SMART
Related trial records

Health condition
Health condition(s) studied:
Cancer 338185 0
Brain metastases 338186 0
Condition category
Condition code
Cancer 334460 334460 0 0
Any cancer
Cancer 334823 334823 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
Preoperative Multi-fraction Pre-Stereotactic radiosurgery (SRS) of the index metastases planned for surgery on consecutive days
- Multi fraction (24Gy in 3 fractions (for lesions >3cm) or 27Gy in 3 fractions for lesions </= 3cm) to the index lesion(s) to be ideally be delivered within 7 days prior to surgery, but up to 14 days is permitted. The last fraction may be delivered on the same day as surgery.
- The radiation Oncologist will prescribe the radiation, define the targets on dedicated planning imaging and review the dosimetry before approving the appropriate radiation plan that fits with the trial planning guidelines and credentialling requirements. Radiation will be delivered by the radiation therapist.
- All Multi fraction radiation treatment should be ideally completed on consecutive days (i.e. over 3 days), however if the second or third fractions fall on a weekend or public holiday the final fraction (s) should be delivered on the first working day that the centre is operational again.
- All participants to be treated with equipment capable of delivering stereotactic cranial radiotherapy (such as CyberKnife, GammaKnife or Linac)
Intervention code [1] 331497 0
Treatment: Other
Description of the comparator or control
Preoperative Single-fraction Pre-Stereotactic radiosurgery (SRS) of the index metastases planned for surgery
- Single fraction (15Gy for lesions >3cm, 18Gy for lesions 2-3cm, 20Gy for lesions </= 2cm) to the index lesion(s) to be ideally be delivered within 7 days prior to surgery, but up to 14 days is permitted. May be delivered on the same day as surgery.
- All participants to be treated with equipment capable of delivering stereotactic cranial radiotherapy (such as CyberKnife, GammaKnife or Linac)
Control group
Active

Outcomes
Primary outcome [1] 342165 0
Cavity local control
Timepoint [1] 342165 0
12 months from randomisation
Secondary outcome [1] 449785 0
Overall survival
Timepoint [1] 449785 0
12 months from randomisation
Secondary outcome [2] 449786 0
Central Nervous System (CNS) death
Timepoint [2] 449786 0
12 months from randomisation
Secondary outcome [3] 449787 0
Distant brain failure
Timepoint [3] 449787 0
Time of death or 24 months from randomisation
Secondary outcome [4] 449788 0
Incidence of Leptomeningeal Disease (LMD)
Timepoint [4] 449788 0
12 months from surgery
Secondary outcome [5] 449789 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms
Timepoint [5] 449789 0
Baseline, 3, 6 and 12 months from surgery
Secondary outcome [6] 449790 0
Early and late adverse events
Timepoint [6] 449790 0
12 months from surgery
Secondary outcome [7] 449791 0
Rate of acute (first day post SRS until surgery) of >= grade 2 adverse reaction event (ARE) in each arm
Timepoint [7] 449791 0
Baseline and day of surgery (prior to surgery)
Secondary outcome [8] 449792 0
Rate of late (>90days post-SRS) of >= grade 2 ARE in each arm
Timepoint [8] 449792 0
3, 6, 12 months from surgery
Secondary outcome [9] 452323 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms
Timepoint [9] 452323 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [10] 465710 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Overall QoL
Timepoint [10] 465710 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [11] 465711 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Physical Functioning
Timepoint [11] 465711 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [12] 465712 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Role Functioning
Timepoint [12] 465712 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [13] 465713 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Emotional Functioning
Timepoint [13] 465713 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [14] 465714 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Cognitive Functioning
Timepoint [14] 465714 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [15] 465715 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Social Functioning
Timepoint [15] 465715 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [16] 465716 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; - Fatigue
Timepoint [16] 465716 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [17] 465717 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Nausea and Vomiting
Timepoint [17] 465717 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [18] 465718 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Pain
Timepoint [18] 465718 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [19] 465719 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Global Health Status / Quality of Life
Timepoint [19] 465719 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [20] 465720 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Dyspnoea
Timepoint [20] 465720 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [21] 465721 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Insomnia
Timepoint [21] 465721 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [22] 465722 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Appetite loss
Timepoint [22] 465722 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [23] 465723 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Constipation
Timepoint [23] 465723 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [24] 465812 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Diarrhoea
Timepoint [24] 465812 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [25] 465813 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Financial difficulties
Timepoint [25] 465813 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [26] 465814 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Overall QoL
Timepoint [26] 465814 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [27] 465815 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Future Uncertainty
Timepoint [27] 465815 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [28] 465816 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Visual Disorder
Timepoint [28] 465816 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [29] 465817 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Motor Dysfunction
Timepoint [29] 465817 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [30] 465818 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Communication Deficit
Timepoint [30] 465818 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [31] 465819 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Headaches
Timepoint [31] 465819 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [32] 465820 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Seizures
Timepoint [32] 465820 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [33] 465821 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Drowsiness
Timepoint [33] 465821 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [34] 465822 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Hair Loss
Timepoint [34] 465822 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [35] 465823 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Itchy Skin
Timepoint [35] 465823 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [36] 465824 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Weakness of Legs
Timepoint [36] 465824 0
Baseline, 3, 6 and 12 months from randomisation
Secondary outcome [37] 465825 0
Quality of Life (QoL); difference in self-reported health outcomes between the two arms; Bladder Control Problems
Timepoint [37] 465825 0
Baseline, 3, 6 and 12 months from randomisation

Eligibility
Key inclusion criteria
• Age >/= 18 years
• Histological or cytological confirmation of solid primary malignancy
• Clinical indication for surgical resection of at least one brain metastasis (index lesion) as per the recommendation by the treating team (Maximum of 2 index lesions | Diameter of each index metastases (for surgery) < /= 4cm)
• ECOG performance status < /=2
• Controlled or available treatment options for extra cranial disease

Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
• Considered unsuitable for cranial radiotherapy per local investigator discretion
• Significant neurological symptoms or mass effect on radiology mandating urgent surgery (including but not limited to > 10mm midline shift, acute obstruction to CSF flow, major tumour related haemorrhage)
• Index lesion < 5mm from the optic apparatus or located in the brainstem (unless dosimetry allows subthreshold dose to these structures)
• Anti VEGF therapy within 4 weeks prior to screening
• Prior cranial surgery within 12 months for malignant primary or secondary brain cancer
• Previous radiotherapy to the index lesion/s or WBRT
• WBRT planned immediately after surgery
• MRI evidence of definite diffuse LMD at baseline and/or positive cerebrospinal fluid histology (if performed)
• Not suitable for MRI brain with Gadolinium and follow up
• Active or prior documented inherited hypersensitivity syndromes. For example, scleroderma, and systemic lupus erythematosus

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)
Central randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be performed using the method of minimisation to optimise balance between the stratification factors whilst maintaining the desired allocation ratio of 2:1.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The study is powered based on a Simon 2-stage design for the endpoint of 1-year local failure. 34 evaluable multi-fraction participants will provide 80% power (5% type-one error) to demonstrate failure is <20% if the true rate is 4%. With randomisation (34 intervention: 17 control) and allowing for up to 30% of participants not surviving to the assessment time, the recruitment target total will be 73.

The full analysis set will include all randomised participants. The full analysis set will be used for all efficacy analyses and treatment groups will be compared on the basis of randomised treatment, regardless of the treatment actually received.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2026
Actual
Date of last participant enrolment
Anticipated
1/12/2027
Actual
Date of last data collection
Anticipated
1/07/2028
Actual
Sample size
Target
73
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC

Funding & Sponsors
Funding source category [1] 319447 0
Charities/Societies/Foundations
Name [1] 319447 0
Tour-De Cure
Country [1] 319447 0
Australia
Funding source category [2] 319448 0
Charities/Societies/Foundations
Name [2] 319448 0
Mark Hughes Foundation
Country [2] 319448 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Trans Tasman Radiation Oncology Group
Address
Country
Australia
Secondary sponsor category [1] 321945 0
None
Name [1] 321945 0
Address [1] 321945 0
Country [1] 321945 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 318021 0
Peter MacCallum Cancer Centre Human Research Ethics Committee
Ethics committee address [1] 318021 0
Ethics committee country [1] 318021 0
Australia
Date submitted for ethics approval [1] 318021 0
14/07/2025
Approval date [1] 318021 0
18/11/2025
Ethics approval number [1] 318021 0

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

Contacts
Principal investigator
Name 142890 0
Dr Neda Haghighi
Address 142890 0
Peter MacCallum Cancer Centre 305 Grattan St, Melbourne Victoria 3052
Country 142890 0
Australia
Phone 142890 0
+61 3 8559 8771
Fax 142890 0
Email 142890 0
[email protected]
Contact person for public queries
Name 142891 0
TROG SMART CRA
Address 142891 0
TROG Cancer Research, Waratah, NSW, 2298
Country 142891 0
Australia
Phone 142891 0
+61 2 4014 3911
Fax 142891 0
Email 142891 0
[email protected]
Contact person for scientific queries
Name 142892 0
Neda Haghighi
Address 142892 0
Peter MacCallum Cancer Centre 305 Grattan St, Melbourne Victoria 3052
Country 142892 0
Australia
Phone 142892 0
+61 3 8559 8771
Fax 142892 0
Email 142892 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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.