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Trial registered on ANZCTR


Registration number
ACTRN12619001157167
Ethics application status
Approved
Date submitted
24/07/2019
Date registered
19/08/2019
Date last updated
7/12/2020
Date data sharing statement initially provided
19/08/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
A study to test whether images taken by a new handheld medical imaging device can be used to detect the microscopic presence of cancer during breast cancer surgery.
Scientific title
Evaluating the accuracy of the MEprobe for intraoperative assessment of tumour margins in breast cancer: a pilot study
Secondary ID [1] 298829 0
Clinical Trial CT-2018-CTN-04145-1 v1 TGA CTN
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 313785 0
Condition category
Condition code
Cancer 312188 312188 0 0
Breast
Surgery 312189 312189 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Handheld MEprobe scans of the surgical breast cavity will be performed to determine whether residual tumour can be visualised in the breast cavity of patients with positive margins, as determined by post-operative histological assessment of the corresponding excised cavity shavings. The MEprobe will be located in the operating theatre at Fiona Stanley Hospital (FSH). Two engineers will be present during each scan, one to operate the imaging scanner and the other to guide and assist the breast surgeon to use the handheld MEprobe. TGA-approved sterile sheaths routinely used in surgery will be used to cover the sterilized MEprobe and associated cables to ensure the scanning is performed in a sterile environment.
After completing the wide local excision of breast tissue, the surgeon will use their clinical judgement (which may include intra-operative imaging of the specimen), as is standard practice, to determine which area(s) of the resection bed requires additional removal of breast tissue (i.e. cavity shavings). On suitable areas, the surgeon will insert the tip of the MEprobe, clad in its sterile sheath, into the wound and scan the cavity before excising the cavity shaving. All specimens will be orientated with suture markings and radio-opaque clips/markers as per standard operating procedures before being placed in a labelled specimen container for pathology. This procedure will be repeated until all clinically relevant cavity shavings have been excised. Multiple images may be acquired from each patient and each image will be 7×7 mm in size and take less than 5 seconds to acquire.
The wide local excision specimen and all cavity shavings will be transported by the research team to PathWest at FSH for validation purposes. Ex vivo micro-elastograms of excised cavity shavings +/- wide local excision specimens transported from surgery to PathWest will be acquired using the micro-elastography benchtop system previously validated by the research team. Following ex vivo scanning, all excised tissue will be fixed, embedded in paraffin, and hematoxylin and eosin (H&E) stained. Histological sections will be prepared, as per standard practice for all excised breast tissue.

Initially, one surgeon (the CPI) will operate and test the new probe on up to 10 study participants. Detailed feedback from the surgeon will be used to generate operator training guidelines and a protocol for study use during in vivo scanning of the resection bed during breast-conserving surgery. Up to four additional surgeons operating at FSH will then be trained in the use of the probe. They will provide feedback to refine the operator training guidelines so that the technique can be standardised for the accuracy arm of the study which aims to determine the accuracy (including sensitivity and specificity) of the MEprobe for use in classifying in vivo breast tissue as either benign or cancerous.

To determine the accuracy of the MEprobe a blinded reader study will be done. Blinded readers, including surgeons, radiologists, engineers and pathologists, will be trained to read breast micro-elastograms using a training data set. The training data set will include histology-validated micro-elastograms from a previous benchtop micro-elastography study of ex vivo breast tissue in addition to MEprobe study images acquired before recruitment into the accuracy arm of the study. The training data set findings will establish the evaluation methodology and image feature criteria for identifying cancer. As part of the training procedure, readers will be taught how to use ImageJ, a widely-used software that is needed to visualise the 3-dimensional micro-elastograms.
Intervention code [1] 315097 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 320819 0
The composite primary (statistical) outcome is to determine the accuracy (including both the Sensitivity and Specificity) of the MEprobe for use in classifying in vivo breast tissue as either benign or cancerous. Histology-validated images will be used in a blinded reader study to evaluate the accuracy of probe acquired images using the following approach.

In vivo micro-elastogram images will be spatially co-registered with histology guided by information contained in the routine pathology report. This will involve a two-step process.

• Step 1: the smaller in vivo MEprobe images (7×7mm) of the cavity shavings will be co-registered with the larger ex vivo benchtop image (maximum size 45×45mm).

• Step 2: the ex vivo benchtop image will be co-registered with the routinely acquired histology images. The ex vivo images will form the link between in vivo MEprobe image and histology.

The histology images that correspond to the micro-elastogram will be reviewed by a pathologist to both confirm the absence/presence of cancer on the margin and report on the closest distance of cancer from the scanned margin.
These histology-validated images acquired will be used in a blinded reader study (n=110) for evaluating the accuracy of using the MEprobe with respect to discriminating between cancerous and non-cancerous breast tissue.
Blinded readers, including surgeons, radiologists, engineers and pathologists, will be trained to read breast micro-elastograms using a training data set supplemented with a Reader Decision Tree. The training data set will include histology-validated micro-elastograms from a previous benchtop micro-elastography study of ex vivo breast tissue in addition to MEprobe study images acquired before recruitment into the accuracy arm of the study. The training data set findings will establish the evaluation methodology and image feature criteria for identifying positive margins. As part of the training procedure, readers will be taught how to use ImageJ, a widely-used software that is needed to visualise the 3-dimensional micro-elastograms. Study images will be randomised prior to analysis.
Sensitivity will be defined as the percentage of cavity shavings with breast cancer who are correctly identified by Blinded Readers interpreting MEprobe research images. Specificity is the percentage of cavity shavings without the cancer who are correctly excluded by the MEprobe.
• Sensitivity = TP/(TP + FN)
• Specificity = TN/(TN + FP)

(Abbreviations: TP, true positive; TN, true negative; FP, false positive; FN, false negative.)
Timepoint [1] 320819 0
Medical device data (i.e. research images) will be acquired on the day of the participant's breast conserving surgery. Imaged excised breast tissue specimens will undergo routine pathology within a week of surgery.
Primary outcome [2] 320821 0
Safety evaluation consisting of assessment of all adverse events following the use of the MEprobe medical imaging device during routine breast conserving surgery.
Possible post-surgical complications (i.e. adverse events) include
• Pain
• Erythema
• Axillary Swelling
• Warmth/inflammation (surgical incision)
• Infection/sepsis
• Fever
• Rashes
Adverse events will be captured during the patient’s follow-up visit at the Breast Clinic in combination with review of routine hospital medical records by the treating doctor. Adverse events will also be collected by the research team during surgery. The investigators will review all adverse events and follow them to resolution. Where applicable, the Data Safety Monitoring Board will review these events and consider their significance with regard to continuation of the trial.
Timepoint [2] 320821 0
Adverse events will be captured during surgery, at the follow-up appointment (approximately 2 weeks post-surgery) and, where necessary, followed up until event has resolved.
Secondary outcome [1] 373532 0
Nil
Timepoint [1] 373532 0
Nil

Eligibility
Key inclusion criteria
• Female, 18 years or over.
• Histologically confirmed invasive or in-situ carcinoma
• Candidate for breast conserving surgery based on clinical and radiological evaluation.
• Completion of a signed and dated, written, informed consent obtained prior to participation.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
• Pregnant
• Lactating
• Highly dependent on medical care who may be unable to give consent
• Cognitive impairment, an intellectual disability or a mental illness who may be unable to give consent

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



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
TStatistical methods / analysis: The primary (statistical) endpoint is to determine the accuracy (sensitivity and specificity) of the MEprobe for use in classifying in vivo breast tissue as either benign or cancerous.
The primary endpoint will be measured after first completing the following two objectives:
1. Develop a protocol for breast cancer surgeons to use the MEprobe to assess regions of the breast cavity for the microscopic presence of cancer ) during breast cancer surgery and
2. Determine whether in vivo results from the MEprobe can be used to show structural differences between cancerous and non-cancerous tissue within the breast cavity.
The study findings and observations from these first two objectives will be used to finalize the procedures and methods for assessing the primary endpoint. Histology-validated images will be used in a blinded reader study to evaluate the accuracy of probe acquired images.
Based on our previous study evaluating the accuracy of the benchtop micro-elastography system on ex vivo tissue, it is anticipated that n=110 will be needed to power the primary endpoint, with an additional n=30 cases for meeting the study objectives defined in the preceding paragraph. The ability to anticipate sample size is, however, limited, because it will depend on the prevalence of tumour in the scanned breast tissue. Consequently an interim analysis will be used to determine if (a) a stop for futility is warranted or (b) additional subjects need to be enrolled.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
12/08/2019
Date of last participant enrolment
Anticipated
15/08/2022
Actual
Date of last data collection
Anticipated
19/09/2022
Actual
Sample size
Target
140
Accrual to date
18
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 14301 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 27299 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 303380 0
Commercial sector/Industry
Name [1] 303380 0
OncoRes Medical Pty Ltd
Country [1] 303380 0
Australia
Primary sponsor type
University
Name
University of Western Australia
Address
35 Stirling Hwy, Crawley WA 6009
Country
Australia
Secondary sponsor category [1] 303416 0
None
Name [1] 303416 0
Address [1] 303416 0
Country [1] 303416 0
Other collaborator category [1] 280867 0
Commercial sector/Industry
Name [1] 280867 0
PathWest
Address [1] 280867 0
PathWest
Fiona Stanley Hospital
Tissue Pathology | Anatomical Pathology FSH
Robin Warren Drive
MURDOCH Western Australia 6150
Country [1] 280867 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303912 0
South Metropolitan Health Service Human Research Ethics Committee
Ethics committee address [1] 303912 0
Ethics committee country [1] 303912 0
Australia
Date submitted for ethics approval [1] 303912 0
25/06/2018
Approval date [1] 303912 0
18/07/2018
Ethics approval number [1] 303912 0
RGS0000000499

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

Contacts
Principal investigator
Name 95222 0
Prof Christobel Saunders
Address 95222 0
Medical School of Surgery
The University of Western Australia
35 Stirling Hwy (M507)
Crawley WA 6009
Country 95222 0
Australia
Phone 95222 0
+61 8 6151 1122
Fax 95222 0
Email 95222 0
christobel.saunders@uwa.edu.au
Contact person for public queries
Name 95223 0
Brendan Kennedy
Address 95223 0
Laboratory Head/Senior Research Fellow
The University of Western Australia & Harry Perkins Institute of Medical Research
6 Verdun Street
Nedlands Western Australia 6009
Australia
Country 95223 0
Australia
Phone 95223 0
+61 8 6151 1085
Fax 95223 0
Email 95223 0
brendan.kennedy@uwa.edu.au
Contact person for scientific queries
Name 95224 0
Brendan Kennedy
Address 95224 0
Laboratory Head/Senior Research Fellow
The University of Western Australia & Harry Perkins Institute of Medical Research
6 Verdun Street
Nedlands Western Australia 6009
Australia
Country 95224 0
Australia
Phone 95224 0
+61 8 6151 1085
Fax 95224 0
Email 95224 0
brendan.kennedy@uwa.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.