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Trial registered on ANZCTR


Registration number
ACTRN12613000684729
Ethics application status
Approved
Date submitted
10/08/2012
Date registered
21/06/2013
Date last updated
26/06/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
Comparative evaluation of Contrast Enhanced Spectral Mammography (CESM) and Contrast Enhanced Magnetic Resonance Imaging (CEMRI) for local staging of breast cancer: the CESM V study
Scientific title
Comparative evaluation of Contrast Enhanced Spectral Mammography (CESM) and Contrast Enhanced Magnetic Resonance Imaging (CEMRI) for local staging of breast cancer: the CESM V study
Secondary ID [1] 281006 0
Nil
Universal Trial Number (UTN)
U1111-1141-3342
Trial acronym
The CESM V Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Local staging of primary breast cancer 287142 0
Condition category
Condition code
Cancer 287463 287463 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
CESM is carried out on commercially available equipment approved for diagnostic use in Australia, a device (Senographe DS - GE Healthcare Australia, Rydalmere, NSW) which is capable of delivering dual energy x-rays in quick succession, with both a normal low Kvp and a higher energy (45-50kVp) exposure. An injection of non-ionic iodinated contrast (1.5mg/kg delivering 350mg I/mL) is given via a catheter in an antecubital vein using a power injector at a rate of 3mL/s. Two minutes later, standard mammographic views (CC and MLO of both breasts) are performed with dual-energy exposures. All four views are obtained within 4 minutes of the injection. The high energy and low energy exposures are subtracted from one another taking advantage of the K-edge of iodine producing images which demonstrate areas of contrast enhancement. The extra exposure is associated with minor increase in radiation dose to the breast of 20% per image.
Intervention code [1] 285465 0
Diagnosis / Prognosis
Comparator / control treatment
Comparison will be made with the findings on Contrast Enhanced Magnetic Resonance Imaging (CEMRI)of the breast.
Breast CEMRI will be performed using standard departmental protocols which use a dedicated breast coil to obtain a T2 weighted sequence, T1 weighted pre contrast images, then T1 post contrast images following injection of 0.1mmol/kg gadolinium GDTA (Magnevist, Bayer Healthcare) with multiple post contrast images acquired every 90 seconds.
The current imaging gold standard technique is contrast enhanced MRI. This will be performed on a 1.5T MRI machine using a dedicated breast coil. Sequences will include T2 weighted sequence, T1 weighted pre contrast images, then T1 post contrast images following injection of 0.1mmol/kg gadolinium GDTA (Magnevist, Bayer Healthcare) with multiple post contrast images acquired every 90 seconds. A body coil image in coronal plane to show the axillae and infra and supraclavicular regions will also be performed.

Control group
Active

Outcomes
Primary outcome [1] 287727 0
Detection of additional lesions (each classified as benign or suspicious, to allow determination of TP, FP, TN, FN).
Timepoint [1] 287727 0
Time points for assessment of primary outcome: immediately after the CESM and CEMRI studies have been performed, at time results of any core biopsies of these lesions (within 2-3 weeks of the studies), or at time of definitive surgery with review of pathology (usually within 6-8 weeks of diagnosis), or for those lesions not biopsied or excised, review with imaging follow up one year post diagnosis.
Secondary outcome [1] 298726 0
Size of the index malignant lesion(s)
Timepoint [1] 298726 0
Immediately following the CESM and MRI studies when they are reported by the radiologist.
Secondary outcome [2] 303332 0
times taken for the CESM or CEMRI procedure
Timepoint [2] 303332 0
measured at time of these procedures
Secondary outcome [3] 303333 0
times taken by radiologists to read the studies
Timepoint [3] 303333 0
measured at time radiologist fills in the CRF with the results of their assessment of the CESM or CEMRI examination
Secondary outcome [4] 303334 0
Participants will be asked to complete a brief satisfaction survey using a Likert scale and a free text comment
Timepoint [4] 303334 0
Filled in just after they have had their second of the two tests, which depending on the bookings will be the CESM or the CEMRI examination

Eligibility
Key inclusion criteria
-Female of any race or ethnicity.
-Aged 35 years and over.
-Core biopsy proven diagnosis of invasive breast cancer in one or both breasts.
-Participant fit to undergo surgical treatment, either breast conservation surgery or mastectomy.
Minimum age
35 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
-Male.
-Unable or unwilling to give informed consent.
-Impaired mobility (good mobility is needed to ensure the CESM can be performed within the required time after the contrast injection is given).
-Presence of breast implants.
-Pregnancy or breast feeding.
-A participant who is not fit for or declines surgical treatment.
-participant who is going to have neoadjuvant chemotherapy
-The breast lesion consists solely of “in-situ” carcinoma on core biopsy histology.
-Contraindication to the intravenous use of iodinated or gadolinium-chelated contrast agent, particularly renal insufficiency or allergy.
-Known contraindication to MRI examination, e.g. metallic implant, aneurysm clip

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)
Patients who have been diagnosed with breast cancer and meet the eligibility criteria will be invited to participate by a breast physician or radiologist.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
The participants will all undergo both imaging tests.
Ground truth will be final histopathology in most cases.
Where any extra detected lesions over the index lesion are not surgically removed, core biopsy histology is the gold standard and where no biopsy is performed, follow up with imaging to look for absence of interval change at one year post treatment will be the gold standard.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample size calculation:
The primary outcome of the study is the ability of the two methods to detect additional lesions. The sample size gives 80% power (alpha = 0.05) to detect a difference of one additional lesion as statistically significant if these occur in 20% of patients, with a 15% rate of attrition. This is insufficient to allow a conclusion of equivalence to be drawn, but it will provide a secure foundation for the planning of further studies. The design of this study is powered to achieve the secondary outcome (assessment of the size of the index lesion by CESM compared with MRI). The sample size of 60 subjects gives 95% power (alpha = 0.05) to detect as significant a difference of ±2 mm between the two methods. This will allow a conclusion of equivalence to be drawn if the two methods do not differ by more than ±2 mm.
Power analysis was conducted using PASS 2008 package.
Statistical analysis:
For the primary outcome we will assess the proportion of additional lesions with binomial confidence intervals for each imaging method. The definitive analysis will use a clustered (robust) tobit regression model because the data will be truncated with no cases with zero lesions. The additional detected lesions will be categorised based upon biopsy results and/or imaging follow-up.
For the secondary outcome, we expect the size of the lesion to follow a log-normal distribution and so a geometric mean will be used for descriptive purposes and a Wilcoxon sign-rank test will be used to compare the CESM and MRI estimates. Definitive analysis will use a linear regression model with a ln-transformed size as the dependent variable.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 1142 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 6989 0
6000 - Perth

Funding & Sponsors
Funding source category [1] 285791 0
Other
Name [1] 285791 0
Department of Diagnostic and Interventional Radiology Special Purpose Account
Address [1] 285791 0
Division of Imaging Services
Royal Perth Hospital
Wellington Street
Country [1] 285791 0
Australia
Primary sponsor type
Hospital
Name
Royal Perth Hospital
Address
Wellington Street
Perth WA 6001
Country
Australia
Secondary sponsor category [1] 284614 0
Commercial sector/Industry
Name [1] 284614 0
GE Healthcare
Address [1] 284614 0
Unit 1, 24-28 Belmont Avenue
Belmont WA 6104

Country [1] 284614 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287800 0
The Royal Perth Hospital Human Research Ethics Committee
Ethics committee address [1] 287800 0
Level 5 Colonial House,
Royal Perth Hospital
GPO Box X2213 Perth WA 6001
Ethics committee country [1] 287800 0
Australia
Date submitted for ethics approval [1] 287800 0
Approval date [1] 287800 0
26/07/2012
Ethics approval number [1] 287800 0
2012/048

Summary
Brief summary
Contrast Enhanced Magnetic Resonance Imaging (CEMRI) of the breast is the most accurate imaging test to show the size and extent of breast cancer. A new technique, Contrast Enhanced Spectral Mammography (CESM) is also capable of showing areas of abnormal blood flow in the breast that are associated with breast cancer, similar to the way in which contrast enhanced breast MRI works.

Due to limited availability and cost, CEMRI is not routinely used to assess all breast cancers in Australia; rather its use is reserved to answer specific questions. Whilst approved for use in Australia by the Therapeutic Goods Administration (TGA), CESM is not routinely used for breast cancer assessment as its role in planning treatment is not yet clear.

This study aims to see whether this new technique is as effective as CEMRI in showing the full extent of cancer in the breast - a finding that has been suggested in other studies of CESM. We hope that proof of this will allow more accurate assessment of women with potential cancerous areas in their breasts without the need for CEMRI, which is not suitable for everyone and not widely available due to cost and limited access to MRI machines.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34562 0
Dr Donna Taylor
Address 34562 0
Department of Diagnostic and Interventional Radiology
Royal Perth Hospital
Box X2213 GPO,
Perth 6847
Country 34562 0
Australia
Phone 34562 0
61 8 92242125
Fax 34562 0
61 8 92243764
Email 34562 0
donna.taylor@health.wa.gov.au
Contact person for public queries
Name 17809 0
Dr Donna Taylor
Address 17809 0
Department of Diagnostic and Interventional Radiology
Royal Perth Hospital
Box X2213 GPO,
Perth 6847
Country 17809 0
Australia
Phone 17809 0
61 8 92242125
Fax 17809 0
61 8 92243764
Email 17809 0
donna.taylor@health.wa.gov.au
Contact person for scientific queries
Name 8737 0
Dr Donna Taylor
Address 8737 0
Department of Diagnostic and Interventional Radiology
Royal Perth Hospital
Box X2213 GPO,
Perth 6847
Country 8737 0
Australia
Phone 8737 0
61 8 92242125
Fax 8737 0
61 8 92243764
Email 8737 0
donna.taylor@health.wa.gov.au

No information has been provided regarding IPD availability
Summary results
No Results