Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000803291
Ethics application status
Approved
Date submitted
3/05/2018
Date registered
11/05/2018
Date last updated
11/05/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Improving treatments for brain metastases through advanced imaging
Scientific title
PET/MR imaging study of breast cancer brain metastases to quantify relationships between blood perfusion dynamics and uptake of pertuzumab
Secondary ID [1] 294780 0
None
Universal Trial Number (UTN)
Trial acronym
BoNSAI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
metastatic breast cancer 307701 0
brain metastases 307702 0
Condition category
Condition code
Cancer 306762 306762 0 0
Breast
Cancer 306771 306771 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Breast cancer patients with radiologically confirmed brain metastases will be administered ONCE with up to 10mg of a pertuzumab-[89]Zr PET tracer, and 50mg of unconjugated pertuzumab (loading dose to minimise nonspecific uptake of the tracer) by intravenous infusion. A Registered Nurse will administer the pertuzumab under supervision of a Medical Officer. On the day of administration, and on 1-2 occasions during the following week, brain tumour uptake of the tracer will be quantified by PET-MR imaging. Imaging will be performed by an accredited Nuclear Medicine Technologist, with supervision by a Medical Officer.
Intervention code [1] 301105 0
Diagnosis / Prognosis
Intervention code [2] 301106 0
Early detection / Screening
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 305753 0
Assess blood perfusion dynamics by quantifying ktrans, the rate of gadolinium entry to the tumour interstitium. This will be done computationally for whole tumours and also within multiple smaller regions-of-interest (ROIs) specified in the three-dimensional MRI images.
Timepoint [1] 305753 0
The day of tracer administration (day-1 baseline scan).
Primary outcome [2] 305754 0
Proportion of the administered dose of [89]Zr-pertuzumab taken up in brain metastases from both HER2+ and HER2-negative breast cancer. Standard, contrast-enhanced MRI will be used to anatomically locate brain lesions, and tracer uptake information will be acquired simultaneously with a PET scan. The PET signal intensity in brain metastases will be expressed as a ratio of the administered dose, accounting for isotope decay over time. This will be done computationally for whole tumours, and also within the ROIs specified as part of primary outcome 1.
Timepoint [2] 305754 0
The day of tracer administration (day-1 baseline scan), plus 1-2 additional scans within the following week (for example, days 5 and 7). Multiple timepoints are required to achieve this outcome.
Primary outcome [3] 305835 0
Qualify the minimum brain lesion size that can be identified with the [89]Zr-Ptz tracer, by comparing the presence and sizes of discrete PET signals to those achieved with contrast-enhanced MRI alone.
Timepoint [3] 305835 0
The day of tracer administration (day-1 baseline scan), plus 1-2 additional scans within the following week (for example, days 5 and 7). Multiple timepoints are required to achieve this outcome.
Secondary outcome [1] 346373 0
Composite outcome: Degree of pertuzumab internalisation and putative effects on HER2 signalling will be assessed using microradiography or immunohistochemistry analysis of brain tumour tissue in cases where neurosurgical material is available shortly after the imaging study (i.e. patients are scheduled for craniotomy and tumour resection as part of their management plan, and they consent to donating tissue in excess of diagnostic requirements for research purposes).
Timepoint [1] 346373 0
Approximately 2 weeks after tracer administration.
Secondary outcome [2] 346570 0
Feasibility of PET-MRI with the [89]Zr-pertuzumab tracer for imaging metastatic disease outside the brain. The presence of HER2-expressing lesions outside the brain will be assessed by full-body PET-CT in addition to brain PET-MR. This will only be performed for patients whose managing clinicians request a full-body scan because (re-)staging is required for clinical management anyway. A standard clinical diagnostic CT assessment will be performed by a qualified Radiologist, with simultaneous acquisition of PET data. We will then determine whether the PET images provide any information above and beyond the benefit of CT scanning in each particular case.
Timepoint [2] 346570 0
Day 5 after tracer administration. For any PET-CT candidates, the PET-CT scan will be performed in addition to PET-MRI procedures.

Eligibility
Key inclusion criteria
- Adults at least 18 years of age
- History of breast cancer with HER2 status confirmed according to standard diagnostic criteria
- One or more new or recurrent metastatic brain tumour(s) diagnosed radiologically
- Willing and able to tolerate multiple rounds of imaging
- Willing and able to provide informed consent & attend appointments
- Adequate kidney function (eGFR>30) for Gad-DTPA excretion
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of intolerance or hypersensitivity to pertuzumab
- Leptomeningeal disease
- Prior surgical resection of lesions in the same hemisphere within 4 weeks
- Prior radiation treatment of proximal lesions
- History of congestive heart failure or left ventricular dysfunction (LVEF <50%)
- Active infection
- Claustrophobia
- Pregnant or breastfeeding now or in the near future

Study design
Purpose of the study
Diagnosis
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
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/06/2018
Actual
Date of last participant enrolment
Anticipated
15/05/2020
Actual
Date of last data collection
Anticipated
30/05/2020
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 10830 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 22575 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 299387 0
Government body
Name [1] 299387 0
Metro North Hospital and Health Service
Country [1] 299387 0
Australia
Funding source category [2] 299390 0
Other Collaborative groups
Name [2] 299390 0
Breast Cancer Trials (BCT)
Country [2] 299390 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
The University of Queensland
Chancellor's Pl
St Lucia, QLD 4072
Country
Australia
Secondary sponsor category [1] 298666 0
Hospital
Name [1] 298666 0
Metro North Hospital and Health Service
Address [1] 298666 0
Royal Brisbane and Women's Hospital,
7 Butterfield St,
Herston QLD 4029
Country [1] 298666 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300290 0
Royal Brisbane & Women's Hospital Human Research Ethics Committee
Ethics committee address [1] 300290 0
Ethics committee country [1] 300290 0
Australia
Date submitted for ethics approval [1] 300290 0
29/08/2016
Approval date [1] 300290 0
12/09/2016
Ethics approval number [1] 300290 0
HREC/16/QRBW/452
Ethics committee name [2] 300294 0
The University of Queensland Human Research Ethics Committee
Ethics committee address [2] 300294 0
Ethics committee country [2] 300294 0
Australia
Date submitted for ethics approval [2] 300294 0
02/01/2018
Approval date [2] 300294 0
04/01/2018
Ethics approval number [2] 300294 0
2018000001

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

Contacts
Principal investigator
Name 83174 0
Prof Sunil Lakhani
Address 83174 0
UQ Centre for Clinical Research
B71/918 The Royal Brisbane & Women's Hospital
Herston, QLD 4029
Country 83174 0
Australia
Phone 83174 0
+61 7 3346 6052
Fax 83174 0
Email 83174 0
[email protected]
Contact person for public queries
Name 83175 0
Colleen Niland, Clinical Research Nurse
Address 83175 0
UQ Centre for Clinical Research
B71/918 The Royal Brisbane & Women's Hospital
Herston, QLD 4029
Country 83175 0
Australia
Phone 83175 0
+61 7 3346 66021 / 66020
Fax 83175 0
Email 83175 0
[email protected]
Contact person for scientific queries
Name 83176 0
Jodi Saunus, Senior Postdoctoral Fellow
Address 83176 0
UQ Centre for Clinical Research
B71/918 The Royal Brisbane & Women's Hospital
Herston, QLD 4029
Country 83176 0
Australia
Phone 83176 0
+61 7 3346 6030
Fax 83176 0
Email 83176 0
[email protected]

No information has been provided regarding IPD availability


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.