Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000329561
Ethics application status
Approved
Date submitted
22/03/2015
Date registered
10/04/2015
Date last updated
28/07/2022
Date data sharing statement initially provided
18/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Double-blinded randomised trial of prophylactic dexamethasone versus placebo in stereotactic radiotherapy to 1-5 brain metastases
Scientific title
Double-blinded randomised trial of prophylactic dexamethasone versus placebo in stereotactic radiotherapy to 1-5 brain metastases, assessing symptomatology and quality of life.
Secondary ID [1] 286025 0
Nil
Universal Trial Number (UTN)
U1111-1166-3688
Trial acronym
Stereodex Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Brain metastases 293997 0
Condition category
Condition code
Cancer 294291 294291 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Dexamethasone 4 mg orally daily on day(s) of stereotactic radiotherapy (SRT) and one day after (ie. 2 or 4 days, depending on duration of prescribed SRT)

Instructions will be provided to participant on prescription. Verbal reinforcement will also be available during routine treatment reviews.
Intervention code [1] 291008 0
Treatment: Drugs
Comparator / control treatment
Placebo (lactose powder in gelatine capsule)

(if patients develop symptoms requiring dexamethasone as per clinician's assessment, dexamethasone can be prescribed up to a total dose of 12 mg per day, if prescribed during the period of study medication ie. on day(s) of SRT and one day following)
Control group
Placebo

Outcomes
Primary outcome [1] 294096 0
Changes or development of symptoms post-stereotactic radiotherapy (SRT) to brain metastases

Instrument: MD Anderson Symptom Inventory - Brain Tumor questionnaire: mean Symptom Severity and Symptom Interference subscales
Timepoint [1] 294096 0
On the first day of SRT (pre-treatment) and days 1, 2, and 7 post-treatment
Secondary outcome [1] 312504 0
Rate of initiation of dexamethasone

Assessed by the proportion of patients in each treatment arm who required initiation of dexamethasone
Timepoint [1] 312504 0
First 30 days following commencement of stereotactic radiotherapy
Secondary outcome [2] 312505 0
Predictive factors for initiation of dexamethasone

Pre-determined factors would be evaluated for association with initiation of dexamethasone.
(factors: planned target volume, extent of oedema, number of treated brain metastases, presence of midline shift, presence of impingment of ventricles, tumour location, symptom score pre-treatment, V12 Gy)
Timepoint [2] 312505 0
First 30 days following commencement of stereotactic radiotherapy to brain metastases
Secondary outcome [3] 312506 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 [3] 312506 0
Baseline, Day 7 post-treatment, and 3- and 6- month follow up

Eligibility
Key inclusion criteria
1 Number of brain metastases – 1-5 brain metastases (as defined on the MRI brain); at least one lesion planned for SRT
2 Non-primary brain tumour
3 ECOG performance status 0-2
4 Expected life expectancy of >6 months
5 Not on dexamethasone for at least 7 days preceding treatment
6 Willing or able to complete questionnaires by themselves
7 Willing to be contacted by the study investigators in first 30 days following treatment for follow up
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1 More than 5 untreated brain metastases
2 Leptomeningeal metastases
3 Contraindications or comorbidities which may be seriously affected by dexamethasone – uncontrolled diabetes, previous psychosis secondary to dexamethasone
4 Inability to complete MRI
5 Planned cytotoxic chemotherapy during SRT
6 Other tumour types – primary germ cell tumour, small cell carcinoma, haematological malignancies
7 Brain metastases unsuitable for SRT (eg: located <2 mm of the optic chiasm)
8 Pregnant or lactating women
9 Men or women of childbearing potential who are unwilling to employ adequate contraception throughout study

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Double-blinded - treating doctors, investigators, and participants will be blinded to the study medication.

Randomisation performed by the clinical trials pharmacy, who is uninvolved in study design and execution of the trial, other than randomisation and dispensing of study medication (ie. role of central randomisation).

Dexamethasone and placebo have the same appearance.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation is used (computer generated).
1 stratification factor: 1 versus 2-5 brain metastases
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size:
The MDASI-BT Symptom Severity and Symptom Interference subscales range from 0 to 10.

In a study on patients with brain metastases using these subscales, patients with good performance status reported a mean Symptom Severity subscale score of 1.21 (SD=1.11) while patients with a poor performance status reported a mean score of 2.55 (SD=1.62). For the Symptom Interference subscale, patients in the good performance status group had a mean score of 1.76 (SD=2.17) while patients with a poor performance status reported a mean score of 4.27 (SD=2.96)
It is hypothesised that patients in the placebo arm will likely develop symptoms following SRT, causing a decline in their performance status and a deterioration, from baseline, in the mean severity subscale score of 1.6. Similarly, it is expected that there might be a deterioration, from baseline, in the interference subscale score of 2.5. These scores were taken from normative data of a similar patient population. In the dexamethasone arm, and for each subscale, mean scores post completion of SRT are expected to be similar to their respective baseline mean scores.

With 30 evaluable patients in each arm, the power of the 5% level F-test for the treatment by time interaction is, under a conservative scenario in which more than 98% of the total variation in subscale scores is between assessments within individuals, and when the “total” standard deviations and conjectured declines are as given above, approximately 80%.

A total of 64 participants will be randomised to account for potential dropouts.

Analysis:
Intention-to-treat analysis

The analysis of the primary endpoint will be based on a linear mixed model that will be fitted using the method of restricted maximum likelihood (REML). The null hypothesis, that there is no interaction between assessment times and treatment arms (placebo and dexamethasone) will be tested using an F-test conducted at the 5% significance level (a=0.05). The p-value for this test will be reported together with a two-way table of predicted means (time by arm) and their associated 95% confidence intervals.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
20/04/2015
Actual
24/04/2015
Date of last participant enrolment
Anticipated
Actual
28/04/2022
Date of last data collection
Anticipated
27/10/2022
Actual
Sample size
Target
64
Accrual to date
Final
64
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 3356 0
The Alfred - Prahran
Recruitment hospital [2] 15929 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 9135 0
3004 - Melbourne
Recruitment postcode(s) [2] 29396 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 290619 0
Hospital
Name [1] 290619 0
William Buckland Radiotherapy Centre
Country [1] 290619 0
Australia
Primary sponsor type
Hospital
Name
William Buckland Radiotherapy Centre
Address
55 Commercial Road, Melbourne, VIC 3004
Country
Australia
Secondary sponsor category [1] 289603 0
None
Name [1] 289603 0
Address [1] 289603 0
Country [1] 289603 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294935 0
Alfred Health Ethics Committee
Ethics committee address [1] 294935 0
Ethics committee country [1] 294935 0
Australia
Date submitted for ethics approval [1] 294935 0
Approval date [1] 294935 0
06/03/2015
Ethics approval number [1] 294935 0
Ethics committee name [2] 305415 0
Princess Alexandra Hospital Ethics Committee
Ethics committee address [2] 305415 0
Ethics committee country [2] 305415 0
Australia
Date submitted for ethics approval [2] 305415 0
Approval date [2] 305415 0
Ethics approval number [2] 305415 0
HREC/2018/QMS/48724

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

Contacts
Principal investigator
Name 54302 0
Dr Jeremy Ruben
Address 54302 0
William Buckland Radiotherapy Centre
Alfred Health
55 Commercial Road
Melbourne 3002
Country 54302 0
Australia
Phone 54302 0
+61 3 90762337
Fax 54302 0
Email 54302 0
[email protected]
Contact person for public queries
Name 54303 0
Jeremy Ruben
Address 54303 0
William Buckland Radiotherapy Centre
Alfred Health
55 Commercial Road
Melbourne 3002
Country 54303 0
Australia
Phone 54303 0
+61 3 90762337
Fax 54303 0
Email 54303 0
[email protected]
Contact person for scientific queries
Name 54304 0
Jeremy Ruben
Address 54304 0
William Buckland Radiotherapy Centre
Alfred Health
55 Commercial Road
Melbourne 3002
Country 54304 0
Australia
Phone 54304 0
+61 3 90762337
Fax 54304 0
Email 54304 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.