Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001329853
Ethics application status
Approved
Date submitted
8/08/2021
Date registered
29/09/2021
Date last updated
11/01/2024
Date data sharing statement initially provided
29/09/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Pilot Study of Preoperative Stereotactic Radiosurgery for Brain Metastases
Scientific title
Safety and Efficacy of Preoperative Stereotactic Radiosurgery for Treatment of Brain Metastases: A Phase II Study
Secondary ID [1] 304988 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Cancer (brain metastases) 323142 0
Condition category
Condition code
Cancer 320714 320714 0 0
Any cancer
Cancer 321094 321094 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Both Stereotactic Radiosurgery (SRS) and Neurosurgery (NS) are routinely used to treat brain metastases (BM) detected via magnetic resonance imaging (MRI) scanning.

Cancer patients recruited to this trial will receive current standard treatment interventions available (SRS and NS) delivered in a different sequence or order. All trial participants with confirmed BM will be treated with preoperative SRS, followed by neurosurgery within 1-3 days of SRS completion. The purpose of this study is to find out how well tumours in the brain are controlled by using SRS before NS and the side effects related. SRS & NS treatment delivery occurs over a 1-2 week period approximately. Trial participants will also be offered the the option of contributing their tissue and blood samples for laboratory testing related to this study and 'banking' or storage of left over samples for future research.

Stereotactic Radiosurgery (SRS):
SRS is a standard non-surgical radiation therapy used to treat small tumours of the brain, using many precisely focused radiation beams. Stereotactic radiosurgery is not surgery, in the ordinary sense, because there is no incision involved and general anesthesia is not required for adults. SRS can deliver precisely-targeted radiation in fewer high-dose treatments, which can help preserve healthy tissue. SRS is also used to treat the space or cavity left in the brain after the removal of a brain metastasis by surgery. SRS works by distorting and destroying the DNA of tumor cells.

SRS is a specialised type of external beam radiation therapy using focused radiation beams targeting a well-defined tumour. SRS is customised to the individual patient via treatment planning. SRS is planned using specialised radiotherapy planning computer technology according to standard hospital procedure. Patients routinely attend an SRS planning session performed to acquire CT imaging required to plan treatment. This session is performed within 1 week prior to SRS treatment and usually takes 1 hour to complete. In addition a planning MRI will be acquired which also takes about 1 hour. The images from planning CT and MRI scans routinely acquired, are imported into a radiation planning computer. This computer precisely measures the tumour/s identified for treatment with radiation. Using this technology the radiation oncologist and a team of radiation therapists, create a unique computerised three-dimensional treatment plan specific to a patients individual radiation therapy requirements. The treatment plan created is used to guide precise treatment set-up each time a patient attends for SRS and also to deliver the radiation dose with extreme accuracy.

Treatment is given face to face in the radiotherapy department; the duration of each session is up to 1 hour covering initial treatment set-up through to treatment delivery. The number of radiotherapy treatments will depend on the size, location and number of brain metastasis or surgical cavities. The number of treatments can range between 1 and 5 sessions delivered over a maximum of 7 days.

Treatment is delivered using radiotherapy machines operated by radiation therapists under the supervision of a specialist radiation oncology doctor. SRS is monitored throughout the treatment course and is routinely documented in the electronic medical record and treatment planning / delivery system.

Neurosurgery (NS):
NS a an operation performed by a neurosurgeon on the nervous system, especially the brain to remove brain metastastases. Trial participants will receive NS with-in 1-3 days after completing SRS treatment. The approximate duration of the procedure is up to 4-6 hours.

Patients undergoing NS require hospital admission; the length of stay is dependent on the amount of post surgery recovery time required by each patient. Patients are anaesthetised and surgery performed in a hospital operating room. During the hospital stay patient's are monitored regularly by the neurosurgeon and hospital staff. An MRI scan is routinely performed 2 days after NS, to assess the outcome of the operation.

The NS procedure and post-op management is routinely documented in the patient’s electronic medical record. Patient records will be accessed to source NS data for analysis.

After Treatment:
Trial participants will be reviewed at 1 month and 3 months after treatment completion. Follow-up visits will continue 3 monthly during the first year after completing SRS and NS treatment, followed by regular 6 monthly visits until two years after surgery. This follow-up schedule is standard for all cancer patients having SRS and NS treatments.

Optional Translational Sub-Study:
Trial participants consenting to the optional translational sub-study will have blood and tissue collected for molecular/laboratory evaluation before treatment, during SRS, after treatment completion and at the time of post treatment disease progression. Tissue will be accessed from the archived diagnostic sample, the neurosurgery operation sample and where feasible tissue collected at the time of post treatment progression. After the sub-study is completed, any remaining blood and tissue samples collected, will be 'banked' or stored for future approved research.
Intervention code [1] 321378 0
Treatment: Other
Intervention code [2] 321647 0
Treatment: Surgery
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 328536 0
Symptomatic radiation toxicity (grade 2) assessed in accordance with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Timepoint [1] 328536 0
Approximately 4 weeks after treatment completion and then every 3 months after treatment for 1 year post treatment completion.
Secondary outcome [1] 399347 0
Local Recurrence assessed by brain MRI
Timepoint [1] 399347 0
At 1 year post treatment
Secondary outcome [2] 400740 0
Distant Brain Failure assessed by brain MRI
Timepoint [2] 400740 0
At 1 year post treatment
Secondary outcome [3] 400741 0
Leptomeningeal Disease assessed by brain MRI
Timepoint [3] 400741 0
At 1 year post treatment
Secondary outcome [4] 400742 0
Overall Survival assessed by clinical assessment & MRI
Timepoint [4] 400742 0
At 2 years post treatment
Secondary outcome [5] 400743 0
Progression Free Survival assessed by clinical assessment & MRI
Timepoint [5] 400743 0
At 2 years post treatment
Secondary outcome [6] 400744 0
Postoperative Complications Rate assessed by clinical assessment and imaging (CT & MRI)
Timepoint [6] 400744 0
At 1 year post treatment
Secondary outcome [7] 400745 0
Post-operative outcome assessed using MRI
Timepoint [7] 400745 0
At 2 days post-surgery

Eligibility
Key inclusion criteria
Patients aged 18 years or older.
ECOG Performance Status 0, 1 or 2.
Life expectancy at least 6 months.
Prior histopathological diagnosis of cancer other than small cell lung cancer, lymphoma, and germ cell tumours.
MRI of the brain with findings strongly suggestive of metastatic tumour(s) as assessed by the radiologist.
MRI evidence of single or multiple BM lesions amenable for SRS as discussed both by Radiation Oncologist and Neurosurgeon.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Not a surgical candidate per neurosurgeon's discretion.
Disseminated intracranial or leptomeningeal disease.
Neurologically unstable patients or requiring emergent surgical decompression.
Patients with Brain Metastases 5cm or larger.
Cytotoxic Chemotherapy within 7 days prior to SRS.
Anti-Vascular endothelial growth factor (VEGF) therapy within 6 weeks of SRS (risk of fatal brain haemorrhage with surgical resection).
Inability to tolerate SRS (ie, the inability to lie flat in treatment bed).
Contraindication for MRI.
Pregnancy.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
The sample size of at least 30 participants is based on pragmatic considerations. A historical local control rate in this patient population receiving post-operative radiotherapy (XRT) is approximately 80-84% at 12 months. It is anticipated that pre-operative SRS will increase this rate to approximately 92%. If 25 or more of the 30 patients do not experience local failure within 12 months, this will be consistent with a local failure rate of at most 8% based on a one-sided 95% confidence interval.

The rate of participants developing radionecrosis (RN) or adverse events (AE) within 1 year of local treatment will be estimated together with the appropriate two-sided 95% confidence interval.

Local, distant brain and leptomeningeal disease failure will be described as cumulative incidence curves assuming death or evidence of distant disease as competing events. Disease progression (including death) will be analysed using the method of Kaplan-Meier together with 95% confidence intervals at 12 months. Distant brain failure incidence will also be assessed according to number of treated metastasis.

An event chart will also be created showing the pattern of failures for each participant.
Overall survival will be described using Kaplan-Meier methods. The number of neurological and non-neurological deaths will be provided.

The maximum grade of each adverse event for each participant will be described in tabular form as counts and percentages. Use of corticosteroids will be reported as count and percentage.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/11/2021
Actual
4/03/2022
Date of last participant enrolment
Anticipated
30/06/2025
Actual
Date of last data collection
Anticipated
30/06/2027
Actual
Sample size
Target
30
Accrual to date
7
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 20153 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 34882 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 309371 0
Hospital
Name [1] 309371 0
Sydney West Radiation Oncology Network
Country [1] 309371 0
Australia
Primary sponsor type
Government body
Name
Western Sydney Local Health District
Address
Cnr Hawkesbury & Darcy Roads, Westmead NSW 2147
Country
Australia
Secondary sponsor category [1] 310343 0
None
Name [1] 310343 0
Address [1] 310343 0
Country [1] 310343 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309188 0
Western Sydney Local Health District
Ethics committee address [1] 309188 0
Ethics committee country [1] 309188 0
Australia
Date submitted for ethics approval [1] 309188 0
13/10/2021
Approval date [1] 309188 0
10/12/2021
Ethics approval number [1] 309188 0
2021/ETH01348

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

Contacts
Principal investigator
Name 113278 0
Dr Najmun NAHAR
Address 113278 0
Radiation Oncology Network
The Crown Princess Mary Cancer Centre Westmead
Westmead Hospital
166-174 Hawkesbury Rd
Westmead, NSW 2145
Country 113278 0
Australia
Phone 113278 0
+61 02 8890 5200
Fax 113278 0
Email 113278 0
[email protected]
Contact person for public queries
Name 113279 0
Najmun NAHAR
Address 113279 0
Radiation Oncology Network
The Crown Princess Mary Cancer Centre Westmead
Westmead Hospital
166-174 Hawkesbury Rd
Westmead, NSW 2145
Country 113279 0
Australia
Phone 113279 0
+61 02 8890 5200
Fax 113279 0
Email 113279 0
[email protected]
Contact person for scientific queries
Name 113280 0
Najmun NAHAR
Address 113280 0
Radiation Oncology Network
The Crown Princess Mary Cancer Centre Westmead
Westmead Hospital
166-174 Hawkesbury Rd
Westmead, NSW 2145
Country 113280 0
Australia
Phone 113280 0
+61 02 8890 5200
Fax 113280 0
Email 113280 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. Data sharing is subject to the approval of the Chief Investigator, Trial Management Committee, Western Sydney Local Health District and a Human Research Ethics Committee.
When will data be available (start and end dates)?
Data may be made available after publication of the study results (expected by 2027).
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 Chief Investigator, Trial Management Committee, Western Sydney Local Health District and also approval by a 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 via the following email address: [email protected]


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.