Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000689572
Ethics application status
Approved
Date submitted
8/06/2015
Date registered
2/07/2015
Date last updated
28/06/2021
Date data sharing statement initially provided
18/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomised trial of adjuvant versus delayed stereotactic radiotherapy to resection cavity of brain metastases and quality of life outcomes
Scientific title
Randomised trial of adjuvant versus delayed stereotactic radiotherapy to resection cavity of brain metastases and quality of life outcomes
Secondary ID [1] 286828 0
140/15
Universal Trial Number (UTN)
U1111-1170-7552
Trial acronym
StereoCav
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Brain metastases 295209 0
Condition category
Condition code
Cancer 295458 295458 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Observation with 3-monthly MRI brain surveillance (for 24 months, or until there is a clinical reason not to continue, whichever is earlier), and stereotactic radiotherapy on local recurrence following resection of brain metastases
Intervention code [1] 291987 0
Treatment: Other
Comparator / control treatment
Adjuvant stereotactic radiotherapy to resection cavity(s) following resection of brain metastases
(radiotherapy to complete within 6 weeks of surgery)
Control group
Active

Outcomes
Primary outcome [1] 295188 0
Health-related quality of life

Instrument: EORTC QLQ-C30 and Brain Cancer Module BN-20; raw scores transformed to scaled scores ranging 0-100
Timepoint [1] 295188 0
Patient's profile of global quality of life (assessed every 3 months) over the first 12 months from randomisation.
Secondary outcome [1] 314984 0
Overall survival

Measured from the date of randomisation to the date of death.
Timepoint [1] 314984 0
Up to 2 years
Secondary outcome [2] 314985 0
Local (resected metastases) control rate

Defined as recurrence of disease within 1 cm of resected brain metastases on brain imaging (MRI brain preferred)
Timepoint [2] 314985 0
Up to 2 years
Secondary outcome [3] 314986 0
Distant intracranial control rate

Defined as recurrence of disease a distance of >1 cm from previously resected brain metastases on brain imaging (MRI brain preferred)
Timepoint [3] 314986 0
Up to 2 years
Secondary outcome [4] 314987 0
Neurocognitive function

Instrument: measured by a battery of tests assessing different aspects of neurocognition such as memory, attention, processing speed, executive function and verbal fluency.
Timepoint [4] 314987 0
3 months and 6 months from randomisation

Eligibility
Key inclusion criteria
Age >/=18 years
2 Number of brain metastases – 1-4 brain metastases (as defined on the pre-operative MRI brain) and complete resection of the lesions on post-operative imaging performed within 4 weeks of surgery
3 Non-primary brain tumour site
4 ECOG performance status 0-3
5 Expected life expectancy of >6 months
6 Size of each resection cavity – resection cavity must measure < /=5.0 cm in maximal extent on the post-operative MRI obtained within 4 weeks post-surgery.
7 Tumour staging procedures – all standard tumour-staging procedures necessary to define baseline extra-cranial disease status completed < /=42 days prior to registration
8 Willing or able to complete health-related questionnaires by themselves and by a carer/proxy, if available
9 Willing and able to complete neurocognitive assessments
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1 More than 4 untreated brain metastases
2 Prior cranial radiation therapy
3 Leptomeningeal metastases
4 Inability to complete MRI brain
5 Known allergy to gadolinium
6 Remaining unresected brain metastases
7 Planned cytotoxic chemotherapy during stereotactic radiotherapy (SRT)
8 Other tumour types – primary germ cell tumour, small cell carcinoma, or lymphoma
9 Resected cavities unsuitable for SRT (eg. located < /= 2 mm from the optic chiasm)
10 Pregnant or lactating women
11 Men or women of childbearing potential who are unwilling to employ adequate contraception throughout study

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)
Permuted block randomisation is used

1 stratification factor: 1 versus 2-4 brain metastases

Group allocation provided by a dedicated trial coordinator based on computer-generated permuted block randomisation.

Both participant and treating clinician are aware of group allocation following randomisation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
1 stratification factor: 1 versus 2-4 brain metastases resection cavities
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Non-inferiority design as either arm are clinically acceptable management options
Phase
Phase 2
Type of endpoint/s
Bio-equivalence
Statistical methods / analysis
Intention to treat analysis.

The primary HRQOL endpoint will be the patient’s profile of health-related quality of life (HRQOL) over the first 12 months from randomisation. Analyses will be based on contrasts of predicted means that estimate the mean area under the time curve (AUC) of HRQOL scores for each treatment arm. The repeated measurements of the HRQOL score over the first 12 months will be analysed by fitting linear mixed models using restricted maximum likelihood (REML). The F-test will be used to test for a treatment by time interaction and comparisons between treatment groups at each time point will be based on t-tests that utilise the predicted means and standard errors of difference that are recovered from the fitted mixed model. A non-inferiority t-test is used to compare the contrasts of the predicted means that correspond to the trapezoidal rule for calculation of the mean AUC in each treatment arm. The null hypothesis for this test will specify a non-inferiority margin of -109 units (approximately 15% of the corresponding 12-month conjectured AUC in the EORTC Phase III Soffietti 2013 paper) and the test will be one-sided with alpha=0.05.

Sample size:
The sample size for this phase II study has been pragmatically determined. Nevertheless with 40 evaluable patients in a treatment arm, the non-inferiority t-test (one-sided a=0.05) of the null hypothesis that that mean AUC in the observation is more than 109 units below the mean AUC in the adjuvant arm has more than 80% power when the arms are exactly equivalent, the standard deviation of an assessment is 21, and, the intraclass correlation (ICC) (between-patient variance divided by the total variance) is less than 0.5.

The targeted sample size of 42 patients in each arm should be sufficient to allow for potential dropouts.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
6/07/2015
Actual
6/01/2016
Date of last participant enrolment
Anticipated
Actual
26/03/2020
Date of last data collection
Anticipated
26/03/2022
Actual
Sample size
Target
84
Accrual to date
Final
24
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 3852 0
The Alfred - Prahran
Recruitment postcode(s) [1] 9736 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 291375 0
Hospital
Name [1] 291375 0
William Buckland Radiotherapy Centre
Country [1] 291375 0
Australia
Primary sponsor type
Hospital
Name
William Buckland Radiotherapy Centre
Address
55 Commercial Road, Melbourne, VIC 3004
Country
Australia
Secondary sponsor category [1] 290054 0
None
Name [1] 290054 0
Address [1] 290054 0
Country [1] 290054 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295265 0
Alfred Health Ethics Committee
Ethics committee address [1] 295265 0
Ethics committee country [1] 295265 0
Australia
Date submitted for ethics approval [1] 295265 0
Approval date [1] 295265 0
26/05/2015
Ethics approval number [1] 295265 0

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

Contacts
Principal investigator
Name 57690 0
Dr Jeremy Ruben
Address 57690 0
William Buckland Radiotherapy Centre
Alfred Health
55 Commercial Road
Melbourne, Victoria 3002
Country 57690 0
Australia
Phone 57690 0
+61 3 90762337
Fax 57690 0
Email 57690 0
[email protected]
Contact person for public queries
Name 57691 0
Jeremy Ruben
Address 57691 0
William Buckland Radiotherapy Centre
Alfred Health
55 Commercial Road
Melbourne, Victoria 3002
Country 57691 0
Australia
Phone 57691 0
+61 3 90762337
Fax 57691 0
Email 57691 0
[email protected]
Contact person for scientific queries
Name 57692 0
Jeremy Ruben
Address 57692 0
William Buckland Radiotherapy Centre
Alfred Health
55 Commercial Road
Melbourne, Victoria 3002
Country 57692 0
Australia
Phone 57692 0
+61 3 90762337
Fax 57692 0
Email 57692 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
Study data and results are deidentified


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.